Platinol -AQ

Browse PDR's full list of drug information

Platinol -AQ

Classes

Platinum Compounds

Administration

For storage information, see the specific product information in the How Supplied section.
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Pediatrics: Doses 12 mg/m2 or higher: High
Adults: High
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Irritant

Injectable Administration

Due to a critical shortage of FDA-approved cisplatin, a non-FDA licensed product from China, manufactured by Qilu Pharmaceutical Co. Ltd, in conjunction with Apotex Corp., was made available in May 2023. The vial and carton labels are in Chinese and there are differences in the FDA-approved cisplatin product labeling. Read and become familiar with the Dear Healthcare Professional letter, include the labeling and product comparison, which is attached to the letter.
The linear barcode on the imported product label may not register accurately on the U.S. scanning systems. Manually input the imported product information, including the NDC number, into the system and confirm that the linear barcode, if scanned, provides correct information. Follow alternative procedures to assure that the correct drug product is being used and administered to individual patients.
 
Cisplatin is administered intravenously but also may be administered intra-arterially for the treatment of hepatocellular carcinoma.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Adequate renal and hematologic function should be established prior to administration.
To decrease the incidence and severity of nephrotoxicity, patients must receive appropriate pre-treatment hydration. Maintain adequate hydration and urinary output for 24 hours after treatment with cisplatin.
Avoid the use of needles or IV sets with aluminum parts during cisplatin preparation and administration. Aluminum reacts with cisplatin to form a precipitate, causing loss of potency.

Intravenous Administration

Reconstitution of lyophilized powder (FDA-approved product):
50-mL vial: Add 50 mL Sterile Water for Injection, USP to result in a final concentration of 1 mg/mL.
Storage after reconstitution: The reconstituted solution is stable for 20 hours at controlled room temperature (20 to 25 degrees C; 68 to 77 degrees F); do not refrigerate. Protect the reconstituted solution from light if it is removed from the amber vial and will not be used within 6 hours.
 
Dilution (FDA-approved product):
Dilute cisplatin in 1 to 2 liters of a compatible infusion solution, with or without 37.5 g of mannitol.
Storage of cisplatin solution (not reconstituted lyophilized powder): Following initial entry into the amber vial, cisplatin solution is stable for 28 days protected from light or for 7 days under florescent room light.
 
Dilution (Imported Qilu product):
Refer to Dear Healthcare Professional letter, including appendices 1, 2, and 3.
Dilute cisplatin in 1 liter of 0.9% Sodium Chloride Injection.
Imported cisplatin is slightly viscous. After withdrawing the initial solution from the vial, the letter from the manufacturer recommends injecting an appropriate amount of 0.9% Sodium Chloride Injection into the vial shake it to loosen any solution adhered to the inner wall. Remove this solution from the vial and add to the infusion bag. However, the distributor of the imported product (Apotex) has confirmed with ISMP that the full 50 mg/50 mL can be withdrawn from the vial without using the "washing" process described in the letter.
Protect from light.
 
Intravenous infusion:
Administer by slow IV infusion over 6 to 8 hours.

Other Administration Route(s)

Intraperitoneal Administration:
NOTE: Cisplatin is not approved by the FDA for intraperitoneal administration.
After partial or complete draining of the peritoneal cavity, cisplatin is administered via a Tenckhoff catheter or a percutaneously inserted peritoneal dialysis catheter.
Add cisplatin to a pre-warmed 0.9% Sodium Chloride for injection or Lactated Ringer's solution prior to instilling (i.e., body-temperature).
Alternative #1: dilute appropriate dose in 2 liters of warm 0.9% Sodium Chloride solution and administer by gravity flow over 10 minutes. After a 4-hour dwell, drain peritoneal cavity as completely as possible.
Alternative #2: dilute appropriate dose in 2 liters of warm Lactated Ringer's injection and administer by gravity flow over 10 to 12 minutes. After a 15 to 20 minute dwell, drain peritoneal cavity as completely as possible.
Alternative #3: dilute appropriate dose in 500 mL of warm 0.9% Sodium Chloride solution and administer by gravity flow over 15 to 20 minutes. After a 24-hour dwell, drain peritoneal cavity as completely as possible.

Adverse Reactions
Severe

hearing loss / Delayed / 0-60.0
nephrotoxicity / Delayed / 20.0-30.0
renal failure (unspecified) / Delayed / 1.3-14.0
stomatitis / Delayed / 0-1.6
hepatic failure / Delayed / 0-1.0
vomiting / Early / 60.0
nausea / Early / 60.0
ototoxicity / Delayed / 10.0
GI perforation / Delayed / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
Fanconi syndrome / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
hemolytic-uremic syndrome / Delayed / Incidence not known
thrombotic microangiopathy / Delayed / Incidence not known
tumor lysis syndrome (TLS) / Delayed / Incidence not known
progressive multifocal leukoencephalopathy / Delayed / Incidence not known
leukoencephalopathy / Delayed / Incidence not known
seizures / Delayed / Incidence not known
visual impairment / Early / Incidence not known
optic neuritis / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known
new primary malignancy / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known

Moderate

hyponatremia / Delayed / 0-43.0
bone marrow suppression / Delayed / 25.0-30.0
hypomagnesemia / Delayed / 0-22.0
cholestasis / Delayed / 0-1.0
steatosis / Delayed / 0-1.0
dehydration / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
tetany / Early / Incidence not known
blurred vision / Early / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
edema / Delayed / Incidence not known
erythema / Early / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperamylasemia / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known

Mild

anorexia / Delayed / 0-1.6
hiccups / Early / Incidence not known
diarrhea / Early / Incidence not known
alopecia / Delayed / Incidence not known
rash / Early / Incidence not known
tinnitus / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
paresthesias / Delayed / Incidence not known
tremor / Early / Incidence not known
weakness / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
retinal pigment changes / Delayed / Incidence not known
infection / Delayed / Incidence not known
fever / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
malaise / Early / Incidence not known
asthenia / Delayed / Incidence not known

Boxed Warning
Bone marrow suppression, fungal infection, herpes infection, infection, varicella, viral infection

Cisplatin can cause severe bone marrow suppression with fatalities due to infection. Monitor complete blood counts before initiating therapy, prior to each new cycle, and as clinically indicated; an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for myelosuppression. Closely monitor patients for signs and symptoms of infection. Patients with an active infection should be treated prior to receiving cisplatin. Opportunistic infections, including fungal infection, may occur in some patients due to severe myelosuppression. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy. Patients should immediately report any symptoms of severe myelosuppression such as fever, sore throat, or abnormal bleeding.

Peripheral neuropathy

Use cisplatin with caution in patients with pre-existing peripheral neuropathy. Cisplatin can cause a dose-related peripheral neuropathy that becomes more severe with repeated courses of therapy; elderly patients may be more susceptible. Neuropathy may progress after stopping treatment and may be irreversible in some patients. Perform a neurological examination prior to starting cisplatin therapy, at appropriate intervals during therapy, and after completion of therapy. Consider discontinuation of therapy in patients who develop symptomatic peripheral neuropathy.

Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

Cisplatin can cause severe nephrotoxicity including acute renal failure that becomes more prolonged and severe with repeated courses of treatment. Use cisplatin with caution in patients with pre-existing renal disease, elderly patients, patients with dehydration, and patients receiving concomitant therapy with other nephrotoxic medications as they may be more susceptible to cisplatin-related nephrotoxicity; patients with renal impairment may also be at increased risk of cisplatin-related ototoxicity. Consider alternative treatments or reduce the dose of cisplatin for patients with baseline renal impairment or who develop significant reductions in creatinine clearance during treatment. Ensure adequate hydration before, during, and after cisplatin administration. Monitor renal function and serum electrolytes including magnesium prior to initiating therapy and as clinically indicated; consider magnesium supplementation if appropriate.[28393]

Chemotherapy-induced nausea/vomiting

Administer highly effective antiemetic therapy prior to treatment with cisplatin as it is highly emetogenic chemotherapy. Chemotherapy-induced nausea/vomiting occurs in almost all patients treated with cisplatin who do not receive antiemetic therapy and may require discontinuation of therapy.[28393]

Common Brand Names

Platinol, Platinol -AQ

Dea Class

Rx

Description

Non-cell-cycle specific alkylating agent
Used for the treatment of advanced testicular cancer, advanced ovarian cancer, and advanced bladder cancer, as well as many off-label indications
Can cause severe nephrotoxicity; ensure adequate hydration and closely monitor renal function and serum electrolytes

Dosage And Indications
For the treatment of bladder cancer. For the treatment of bladder cancer as a single agent. Intravenous dosage Adults

50 to 70 mg/m2 IV as a single dose once every 3 to 4 weeks depending on the extent of prior exposure to radiation therapy and/or prior chemotherapy. An initial dose of 50 mg/m2 IV once every 4 weeks is recommended in heavily pretreated patients.

For the neoadjuvant treatment of muscle-invasive bladder cancer in combination with methotrexate, doxorubicin, and vinblastine†. Intravenous dosage Adults

70 mg/m2 IV on day 2 in combination with vinblastine (3 mg/m2 IV on days 2, 15, and 22), methotrexate (30 mg/m2 slow IV push on days 1, 15, and 22), and doxorubicin (30 mg/m2 slow IV push on day 2); give every 28 days for 3 cycles (MVAC regimen).

For the first-line treatment of advanced or metastatic bladder cancer, in combination with vinblastine, doxorubicin, and methotrexate†. Intravenous dosage Adults

70 mg/m2 IV on day 2 in combination with methotrexate (30 mg/m2 IV on days 1, 15, and 22), doxorubicin (30 mg/m2 IV on day 2), and vinblastine (3 mg/m2 IV on days 2, 15, and 22) repeated every 28 days (MVAC regimen) for up to 6 cycles has been evaluated in patients with advanced or metastatic transitional cell carcinoma of the bladder in a long-term analysis of a multicenter, randomized, phase III trial. Cisplatin 70 mg/m2 IV on day 1 plus methotrexate (30 mg/m2 IV on days 1, 15, and 22), doxorubicin (30 mg/m2 IV on day 1), and vinblastine (3 mg/m2 IV on days 1, 15, and 22) repeated every 4 weeks was studied in another randomized, phase III trial. All patients in this study received granulocyte colony-stimulating factor (G-CSF) following chemotherapy.

For the first-line treatment of locally advanced or metastatic transitional-cell bladder cancer, in combination with gemcitabine†. Intravenous dosage Adults

70 mg/m2 on day 2 plus gemcitabine 1,000 mg/m2 IV over 30 to 60 minutes on days 1, 8, and 15 repeated every 28 days (GC regimen) for up to 6 cycles was compared with methotrexate 30 mg/m2 on days 1, 15, and 22; vinblastine 3 mg/m2 IV on days 2, 15, and 22; doxorubicin 30 mg/m2 on day 2; and cisplatin 70 mg/m2 on day 2 (MVAC regimen) as first-line therapy for advanced or metastatic transitional cell carcinoma of the bladder in a multicenter, randomized, phase III trial. In a long-term analysis of this study, GC led to nonsignificantly different overall survival (OS) (14 vs. 15.2 months; adjusted hazard ratio (HR) = 0.99; 95% CI, 0.79 to 1.23) and progression-free survival (PFS) (7.7 vs. 8.3 months; adjusted HR = 1.01; 95% CI, 0.81 to 1.25) times compared with MVAC. The 5-year OS (13% vs. 15.3%) and PFS (9.8% vs. 11.3%) rates were nonsignificantly lower with GC compared with MVAC; however, GC was associated with significantly less grade 3 or 4 neutropenic sepsis (1% vs. 12%; p < 0.001) and mucositis (1% vs. 22%; p = 0.001). Treatment-related death was also reported less often in the GC arm (1% vs. 3%).

For the treatment of ovarian cancer. For the first-line treatment of advanced ovarian cancer, in combination with cyclophosphamide (CP regimen). Intravenous dosage Adults

75 mg/m2 IV on day 1, after completion of cyclophosphamide 750 mg/m2 IV on day 1, every 3 weeks for 6 cycles. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Treatment with cisplatin plus cyclophosphamide resulted in an overall response rate of 73% (complete response, 31%) in women with advanced ovarian cancer in a randomized clinical trial; the median progression-free survival (PFS) was 13 months and median survival was 24 months. In another randomized clinical trial, patients with advanced ovarian cancer who received cyclophosphamide plus cisplatin had a median PFS of 11.5 months and median overall survival of 25.8 months.

For first-line treatment of advanced ovarian cancer, in combination with paclitaxel (CT regimen). Intravenous dosage Adults

75 mg/m2 IV on day 1, after completion of paclitaxel (175 mg/m2 IV over 3 hours OR 135 mg/m2 IV over 24 hours, on day 1), every 3 weeks for 6 cycles.[29200] [25761] [19035] [19037] To prevent hypersensitivity reactions, all patients should be premedicated prior to paclitaxel administration.[29200] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. The 3-hour paclitaxel infusion is associated with less myelosuppression but increased neurotoxicity compared with administering paclitaxel over 24 hours.[64313] Treatment with paclitaxel plus cisplatin significantly improved the median progression-free survival (15.5 to 18 months vs. 11.5 to 13 months) and median overall survival (35.6 to 38 months vs. 24 to 25.8 months) compared with cyclophosphamide plus cisplatin in women with advanced ovarian cancer in 2 randomized phase 3 clinical trials.[25761] [19035]

For the first-line treatment of optimally debulked, stage III ovarian cancer in combination with intraperitoneal and intravenous paclitaxel†. Intraperitoneal dosage† Adults

100 mg/m2 intraperitoneally on day 2, following completion of paclitaxel (135 mg/m2 IV over 24 hours) on day 1; intraperitoneal paclitaxel 60 mg/m2 was then administered on day 8. Repeat every 3 weeks for 6 cycles.[32309] To prevent hypersensitivity reactions, all patients should be premedicated prior to paclitaxel administration.[29200] Treatment with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel significantly improved overall survival and progression-free survival in patients with optimally debulked stage III ovarian cancer in a phase 3 trial compared with intravenous cisplatin and paclitaxel.[32309]

For the treatment of advanced ovarian cancer, as monotherapy. Intravenous dosage Adults

75 mg/m2 IV to 100 mg/m2 IV on day 1 every 3 to 4 weeks. Other doses and regimens have been used; consult the literature for specific protocols. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the treatment of testicular cancer. For the treatment of testicular cancer, in combination with bleomycin and etoposide (BEP regimen). Intravenous dosage Adults

20 mg/m2 IV on days 1 to 5, in combination with etoposide (100 mg/m2 IV on days 1 to 5) and bleomycin (30 units IV on days 1, 8, and 15), every 21 days for 3 cycles.[64341] [49371] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In a randomized clinical trial, treatment with BEP resulted in a response rate of 94% of patients with disseminated germ cell tumors compared with 88% for those treated with etoposide plus cisplatin.[49371] In a randomized clinical trial of patients with favorable-prognosis germ-cell cancer, there was not a significant difference between 3 cycles of BEP and 4 cycles in terms of overall or disease-free survival.[64341]

For the treatment of testicular cancer, in combination with etoposide (EP regimen). Intravenous dosage Adults

20 mg/m2 IV on days 1 to 5 in combination with etoposide (100 mg/m2 IV on days 1 to 5), every 21 days for 4 cycles.[64338]   Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In 2 consecutive randomized trials for good-risk metastatic germ cell tumors, 92% of patients treated with CP achieved a complete response (CR), with a relapse rate of 9% after a median follow-up of 7.6 years; the median time to relapse was 10 months.[64338] In another randomized trial of patients with good-risk disseminated germ cell tumor, treatment with EP resulted in a CR rate of 93% compared with 96% in patients treated with vinblastine, bleomycin, cisplatin, cyclophosphamide, and dactinomycin (VAB-6), with a relapse rate of 11% versus 12%, respectively; patients treated with EP had less toxicity than those who received VAB-6.[49372] Treatment with EP resulted in a 90% CR rate in a third randomized controlled trial compared with 88% for patients with good-risk germ cell tumors who received carboplatin plus etoposide (EC); after a median follow-up of 22.4 months, 3% of patients receiving EP relapsed compared with 12% of those who received EC.[49375]

For the treatment of advanced testicular cancer. Intravenous dosage Adults

20 mg/m2 IV on days 1 to 5 per cycles has been administered. Other doses and regimens have been used; consult the literature for specific protocols. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the treatment of testicular cancer, in combination with etoposide, ifosfamide, and mesna (VIP regimen). Intravenous dosage Adults

20 mg/m2 IV on days 1 to 5, in combination with etoposide (75 mg/m2 IV on days 1 to 5), ifosfamide (1,200 mg/m2 IV on days 1 to 5), and mesna (240 mg/m2 IV over 15 minutes before ifosfamide, then 240 mg/m2 IV at 4 and 8 hours from the start of each ifosfamide on days 1 to 5), every 21 days for 4 cycles. Patients who received previous radiation therapy had an initial 25% dose reduction of etoposide and ifosfamide.[29305] [49539] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] Due to a high risk of febrile neutropenia, colony stimulating factors were administered in clinical trials. In a randomized clinical trial, treatment with VIP resulted in a complete response (CR) rate of 37% in patients with advanced, disseminated germ cell tumors compared with 31% in patients treated with bleomycin, etoposide, and cisplatin (BEP); 2-year failure-free survival (64% vs. 60%) and 2-year overall survival (74% vs. 71%) were not significantly different between treatment arms. Grade 3 or higher toxicity was significantly higher in patients who received VIP.[49539]

For the treatment of relapsed testicular cancer, in combination with paclitaxel, ifosfamide, and mesna (TIP regimen). Intravenous dosage Adults

25 mg/m2 IV over 30 minutes on days 2 to 5, in combination with paclitaxel (250 mg/m2 IV by continuous IV infusion over 24 hours on day 1), ifosfamide (1,500 mg/m2 IV over 60 minutes on days 2 to 5), and mesna (300 mg/m2 IV over 15 minutes before ifosfamide, then 300 mg/m2 IV at 4 and 8 hours from the start of each ifosfamide dose on days 2 to 5), every 21 days for 4 cycles. All patients in the randomized clinical trial received prophylactic colony stimulating factors.[64343] [49539] To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine 50 mg IV (or equivalent) 30 to 60 minutes before paclitaxel, and an IV H2-blocker ranitidine 30 to 60 minutes before paclitaxel.[29200] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] Treatment with TIP resulted in a complete response rate of 70% in patients with progressive, metastatic germ cell tumors. After a median follow-up of 69 months, 90% of these patients remained disease-free.[64343]

For the treatment of progressive, disseminated testicular cancer, in combination with vinblastine, ifosfamide, and mesna (VeIP regimen). Intravenous dosage Adults

20 mg/m2 IV once daily on days 1 to 5, in combination with vinblastine (0.11 mg/kg IV push on days 1 to 2), ifosfamide (1,200 mg/m2 IV on days 1 to 5), and mesna (240 mg/m2 IV over 15 minutes before ifosfamide, then 240 mg/m2 IV at 4 and 8 hours from the start of each ifosfamide dose on days 1 to 5), every 21 days for 4 cycles.[29303] [49539] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In a single-arm, open-label trial, treatment with VeIP resulted in a complete response rate of 49.6% in patients with recurrent germ cell tumors previously treated with cisplatin plus etoposide, usually in combination with bleomycin.[29303]

For the treatment of esophageal cancer†. For the treatment of locally advanced or metastatic esophageal cancer, including gastroesophageal junction carcinoma (GEJ), with an epicenter located 1 to 5 cm above the GEJ, not amenable to surgical resection or definitive chemoradiation, in combination with pembrolizumab and fluorouracil†.
NOTE: Pembrolizumab is FDA approved for this indication in combination with cisplatin and fluorouracil.
Intravenous dosage Adults

80 mg/m2 IV on day 1 every 3 weeks for up to 6 cycles. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Administer in combination with fluorouracil (800 mg/m2 IV per day continuously on days 1 to 5, every 3 weeks for up to 24 months) and pembrolizumab (200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression). Administer pembrolizumab prior to chemotherapy when given on the same day. In a randomized clinical trial (KEYNOTE-590), treatment with pembrolizumab plus cisplatin and fluorouracil significantly improved median overall survival (12.4 months vs. 9.8 months) and median progression-free survival (6.3 months vs. 5.8 months) compared with placebo plus cisplatin and fluorouracil in patients with locally advanced or metastatic esophageal/GEJ tumors who were not candidates for surgical resection or definitive chemoradiation. In a prespecified formal test in patients with PD-L1 CPS of 10 or higher, the median overall survival was 13.5 months in pembrolizumab-treated patients compared with 9.4 months for those who received placebo; in an exploratory analysis, the median overall survival was 10.5 months versus 10.6 months, respectively, for patients with PD-L1 CPS less than 10. The overall response rate was also significantly improved in intent-to-treat patients who received pembrolizumab (45% for a median duration of 8.3 months; complete response [CR], 6%) compared with placebo (29% for a median duration of 6 months; CR, 2.4%).

For malignant mesothelioma†. For the treatment of unresectable malignant pleural mesothelioma, in combination with pemetrexed†.
NOTE: Pemetrexed is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage Adults

75 mg/m2 IV over 2 hours on day 1, beginning approximately 30 minutes after the end of the pemetrexed infusion (pemetrexed 500 mg/m2 IV over 10 minutes on day 1), every 21 days. All patients should receive dexamethasone 4 mg PO twice daily for 3 days, beginning the day before pemetrexed administration, to reduce cutaneous reactions. Additionally, supplement with folic acid (400 to 1,000 mcg PO daily) and vitamin B12 (1 mg IM every 3 months) beginning 7 days prior to the first dose of pemetrexed and continuing for 21 days after the last dose to reduce the severity and frequency of hematologic and GI toxicities; after the first dose, vitamin B12 may be given on the same day as pemetrexed. Do not substitute oral vitamin B12 for IM vitamin B12. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Treatment with pemetrexed plus cisplatin significantly improved the median overall survival (OS) (12.1 months vs. 9.3 months) for chemotherapy-naive patients with malignant mesothelioma compared with cisplatin monotherapy in a randomized clinical trial; the median OS was 13.2 months versus 9.4 months, respectively, in patients who received supplementation with folic acid and vitamin B12. The median time to progressive disease (5.7 months vs. 3.9 months) and the tumor response rate (41.3% vs. 16.7%) were also significantly improved in the pemetrexed group of the intent-to-treat population (regardless of supplementation).

For the treatment of malignant mesothelioma in combination with gemcitabine†. Intravenous dosage Adults

100 mg/m2 IV on day 1 in combination with gemcitabine (1,000 mg/m2 IV on days 1, 8 and 15), every 28 days for 6 cycles. Alternately, cisplatin 80 mg/m2 IV on day 1 in combination with gemcitabine (1,250 mg/m2 IV on days 1 and 8), every 21 days for 6 cycles, has also been studied. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the treatment of malignant peritoneal mesothelioma in combination with mitomycin C†. Intraperitoneal dosage Adults

Four to 6 L of isotonic dialysis fluid was circulated at a flow rate of 500 to 700 mL/min and heated to achieve an intraperitoneal temperature between 42 to 45 degrees C. Intraperitoneal chemotherapy with mitomycin 0.5 mg/kg in combination with cisplatin 0.7 mg/kg was administered over 90 minutes. 5-year overall survival was 28.9%; median overall survival was 35.6 months.

For the treatment of previously untreated advanced, unresectable malignant pleural mesothelioma, in combination with pemetrexed and bevacizumab†. Intravenous dosage Adults

75 mg/m2 IV over 2 hours, beginning approximately 30 minutes after the end of the pemetrexed infusion, in combination with pemetrexed (500 mg/m2 IV over 10 minutes on day 1) and bevacizumab (15 mg/kg IV over 30 to 90 minutes on day 1), every 21 days for 6 cycles. After completion of the last cycle, begin maintenance bevacizumab (15 mg/kg IV over 30 to 90 minutes every 21 days) until disease progression or unacceptable toxicity. Premedicate pemetrexed with dexamethasone 4 mg by mouth twice daily for 3 days, beginning the day before pemetrexed administration to reduce cutaneous reactions. Additionally, supplement with folic acid (400 to 1,000 mcg by mouth daily) and vitamin B12 (1 mg IM every 3 months) beginning 7 days prior to the first dose of pemetrexed and continuing for 21 days after the last dose to reduce the severity and frequency of hematologic and GI toxicities; after the first dose, vitamin B12 may be given on the same day as pemetrexed. Do not substitute oral for IM vitamin B12. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the treatment of advanced or recurrent endometrial cancer† in combination with doxorubicin and paclitaxel. Intravenous dosage Adults

50 mg/m2 IV on day 1, given immediately after doxorubicin (45 mg/m2) on day 1, then administer paclitaxel (160 mg/m2) on day 2; give every 21 days. In clinical trials treatment was continued for up to 7 cycles or until disease progression, and filgrastim (5 mcg/kg) was administered on days 3—12. A phase III trial showed an increase in response rate, progression-free survival, and overall survival in patients receiving paclitaxel, doxorubicin, and cisplatin (TAP) vs. cisplatin and doxorubicin alone. Thrombocytopenia and neuropathy were higher in the TAP arm.

For the treatment of gastric cancer†. For the treatment of previously untreated patients with metastatic gastric or gastroesophageal junction adenocarcinoma in combination with trastuzumab and fluorouracil or capecitabine†.
NOTE: Trastuzumab is FDA-approved for this indication in combination with cisplatin and fluorouracil.
Intravenous dosage Adults

80 mg/m2 IV on day 1 in combination with trastuzumab (8 mg/kg IV over 90 minutes on day 1, then 6 mg/kg IV over 30 to 90 minutes every 21 days from day 22) and fluorouracil (800 mg/m2 per day continuous IV infusion on days 1 to 5) or capecitabine (1,000 mg/m2 PO twice daily on days 1 through 14); repeat cycles every 3 weeks. Chemotherapy should be continued up to a maximum of 6 cycles; trastuzumab should be continued until disease progression or unacceptable toxicity. In a phase 3 trial, 594 patients with inoperable, locally advanced, recurrent, or metastatic adenocarcinoma of the stomach or gastroesophageal junction were randomized to receive cisplatin and 5-FU or capecitabine, with or without trastuzumab. Overall survival (13.5 months vs. 11 months), the primary endpoint, and objective response rate (47% vs. 35%) were significantly increased with the addition of trastuzumab. An updated survival analysis conducted 1-year after the final analysis showed a continued overall survival benefit in the trastuzumab arm (13.1 months vs. 11.7 months). In addition, a subgroup analysis revealed an even greater increase in overall survival (18 months vs. 13.2 months) for the trastuzumab arm in patients with high expression of the HER2 protein (FISH-negative and IHC3 +; or, FISH-positive). Cardiac dysfunction (LVEF decrease 10% or more from baseline to an absolute value less than 50%) occurred in 5% of patients who received trastuzumab vs. 1.1% of patients who did not receive trastuzumab.

For the perioperative treatment of gastric cancer in combination with epirubicin and 5-fluorouracil†. Intravenous dosage Adults

60 mg/m2 IV on day 1 in combination with epirubicin 50 mg/m2 IV on day 1 and 5-fluorouracil (5-FU) 200 mg/m2/day continuous IV infusion on days 1 thru 21, repeated every 3 weeks (ECF regimen). Treatment should be given for 3 cycles before and 3 cycles after surgical resection. In a phase III clinical trial, surgery was performed 3 to 6 weeks after the third cycle of preoperative chemotherapy; postoperative chemotherapy was initiated 6 to 12 weeks after surgery. Overall survival was improved in patients who received ECF and surgery vs. surgery alone.

For the treatment of advanced gastric cancer in combination with capecitabine†. Intravenous dosage Adults

80 mg/m2 IV on day 1 in combination with capecitabine 1000 mg/m2 PO twice daily on days 1 thru 14, repeated every 3 weeks until disease progression or unacceptable toxicity. In a phase III clinical trial, 316 patients with advanced gastric cancer were randomized to receive capecitabine/cisplatin (XP) or 5-fluorouracil/cisplatin (FP). The primary objective of the study, which was to confirm non-inferiority of XP compared with FP for progression-free survival (PFS), was met. In the per-protocol population, the median PFS was 5.6 months for XP and 5 months for FP (HR = 0.81, 95% CI 0.63 to 1.04; p < 0.001 vs. non-inferiority margin of 1.25). Once non-inferiority was confirmed, a superiority test was performed. A trend for PFS was shown favoring patients who received XP, however, this difference was not statistically significant (p = 0.0801). Treatment-related adverse events were similar between the treatment arms. Hand-foot syndrome occurred more frequently with XP; vomiting and stomatitis were more frequent with FP.

For the treatment of advanced gastric cancer in combination with epirubicin and capecitabine or fluorouracil (5-FU)†. Intravenous dosage Adults

60 mg/m2 IV on day 1 in combination with epirubicin (50 mg/m2 IV on day 1) and capecitabine (625 mg/m2 PO twice daily on days 1 thru 21) or 5-FU (200 mg/m2/day IV days 1 thru 21), repeated every 3 weeks up to a maximum of 8 cycles. In a phase III trial, 1002 patients with previously untreated esophagogastric cancer were randomized in a 2:2 trial design to receive epirubicin and oxaliplatin with either capecitabine (EOX) or 5-FU (EOF), or epirubicin and cisplatin with either capecitabine (ECX) or 5-FU (ECF). The trial was designed to show non-inferiority in overall survival for the treatment arms containing capecitabine as compared to the treatment arms containing 5-FU. Non-inferiority was met with a median overall survival of 10.9 months for capecitabine-containing arms vs. 9.6 months 5-FU-containing arms (HR 0.86, 95% CI 0.80 to 0.99 with a noninferiority margin of 1.23); toxicity was similar between the capecitabine and 5-FU treatment arms.

For the treatment of advanced gastric cancer, including adenocarcinoma of the gastroesophageal junction, in combination with docetaxel and 5-fluorouracil in patients who have not received prior chemotherapy for advanced disease†.
NOTE: Docetaxel is FDA-approved for the treatment of gastric cancer as part of the TCF (docetaxel, cisplatin, fluorouracil) regimen.
Intravenous dosage Adults

Various cisplatin doses have been incorporated into multiple treatment regimens. Cisplatin 75 mg/m2 IV on day 1 in combination with docetaxel (75 mg/m2 IV on day 1) and fluorouracil (750 mg/m2/day IV on days 1 to 5), has been given every 21 days until disease progression or unacceptable toxicity (TCF regimen). In a phase II/III trial of 445 patients with previously untreated gastric cancer, TCF significantly improved time-to-progression (5.6 months vs. 3.7 months, p=0.0004), the primary endpoint, as compared to cisplatin and fluorouracil alone. Complicated neutropenia occurred more frequently in the TCF arm.

For the first-line treatment of HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in combination with trastuzumab, pembrolizumab, and fluorouracil†.
NOTE: Pembrolizumab is FDA-approved for this indication in combination with trastuzumab, cisplatin, and fluorouracil.
Intravenous dosage Adults

80 mg/m2 IV every 3 weeks for up to 6 cycles. Administer in combination with fluorouracil (800 mg/m2 per day by continuous IV infusion on days 1 to 5 every 3 weeks), pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without disease progression), and trastuzumab (8 mg/kg IV on day 1 of cycle 1, followed 3 weeks later by 6 mg/kg IV every 3 weeks in subsequent cycles). In the clinical trial, treatment with fluorouracil could continue after completion of 6 cycles of cisplatin, per protocol. Administer pembrolizumab prior to trastuzumab and chemotherapy when given on the same day. Treatment with pembrolizumab plus trastuzumab and investigator's choice of chemotherapy (cisplatin plus fluorouracil, or capecitabine plus oxaliplatin) significantly improved objective response rate (74% vs. 52%; complete response, 11% vs. 3.1%) compared with placebo plus trastuzumab and chemotherapy in patients with previously untreated HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma at an interim analysis of a multicenter, randomized phase 3 trial (KEYNOTE-811). The median duration of response was 10.6 months in the pembrolizumab arm compared with 9.5 months in the placebo arm; 65% versus 53% of patients, respectively, had a duration of response of at least 6 months. 

For the treatment of high-risk gestational trophoblastic disease†. Intravenous dosage Adults

60 mg/m2 IV on day 8 in combination with etoposide, methotrexate, leucovorin, and actinomycin D (EMA-EP regimen), repeated every 2 to 3 weeks depending on toxicity. Studies in patients with chemorefractory high-risk gestational trophoblastic disease have shown response rates of higher than 90% with salvage treatment with EMA-EP. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity.

For the treatment of non-Hodgkin's lymphoma (NHL)†. For salvage treatment in NHL, in combination with high-dose cytarabine and dexamethasone†. Intravenous dosage Adults

100 mg/m2 continuous IV infusion over 24 hours on day 1 in combination with cytarabine 2 grams/m2 IV (patients greater than 70 years old: 1 gram/m2 IV) over 3 hours, every 12 hours for 2 doses on day 2, and dexamethasone 40 mg IV/PO once daily on days 1, 2, 3, 4 per cycle; repeated every 3 to 4 weeks.

For the treatment of relapsed or refractory, aggressive NHL in transplant eligible patients, in combination with gemcitabine and dexamethasone (and rituximab for CD20-positive disease)†. Intravenous dosage Adults

75 mg/m2 IV over 1 hour on day 1 in combination with gemcitabine 1,000 mg/m2 IV on days 1 and 8 and dexamethasone 40 mg orally daily on days 1, 2, 3, and 4 (GDP regimen) repeated every 21 days for 2 cycles was evaluated in a randomized, phase III trial (NCIC-CTG LY.12 trial). In patients with CD20-positive lymphoma, rituximab 375 mg/m2 IV was added on day 1 of each treatment cycle (R-GDP regimen). Patients in the trial could receive a third cycle of therapy if they did not achieve a complete or partial response after the second cycle. Patients with CD20-positive lymphoma who received an autologous stem-cell transplant (ASCT) were randomized to receive either rituximab 375 mg/m2 IV every 2 months for 6 cycles or observation starting 28 days post ASCT.

For the treatment of relapsed or refractory diffuse large B-cell lymphoma in transplant eligible patients, in combination with dexamethasone and cytarabine (DHAP regimen) and ofatumumab†. Intravenous dosage Adults

100 mg/m2 as a continuous IV infusion over 24 hours on day 1 as part of the DHAP regimen with dexamethasone 40 mg PO/IV on days 1, 2, 3, and 4 and cytarabine 2 grams/m2 IV over 3 hours every 12 hours for 2 doses on day 2 in combination with ofatumumab 1,000 mg IV on days 1 and 8 of cycle 1 then ofatumumab 1,000 mg IV on day 1 of cycles 2 and 3 was evaluated in a randomized, phase III trial (n = 445; the ORCHARRD trial). Cycles were repeated every 21 days for a total of 3 cycles of therapy. Granulocyte colony-stimulating factor use was recommended as follows: filgrastim 5 micrograms (mcg)/kg on days 6 to 13 or pegfilgrastim 6 mg on day 6 on cycles of therapy with no stem-cell mobilization and filgrastim 5 to 10 mcg/kg on days 6 to 13 on cycles of therapy that were followed by stem-cell mobilization. Central nervous system prophylaxis using intrathecal therapy was permitted. Supportive care during treatment consisted of irradiated blood products, oral antibiotics, and antifungal prophylaxis as clinically indicated.

For the treatment of non-small cell lung cancer (NSCLC)†. For first-line treatment of non-small cell lung cancer (NSCLC) in patients who are not candidates for potentially curative surgery and/or radiation therapy, in combination with paclitaxel†.
NOTE: Paclitaxel is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage Adults

75 mg/m2 IV, after completion of paclitaxel (135 mg/m2 IV over 24 hours on day 1), every 3 weeks. Premedicate all patients with dexamethasone (20 mg PO approximately 12 and 6 hours before paclitaxel), diphenhydramine or equivalent (50 mg IV 30 to 60 minutes before paclitaxel), and either cimetidine (300 mg IV 30 to 60 minutes before paclitaxel) or ranitidine (50 mg IV 30 to 60 minutes before paclitaxel) to prevent severe hypersensitivity reactions.  Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For first-line treatment of unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with docetaxel†.
NOTE: Docetaxel is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage Adults

75 mg/m2 IV over 30 to 60 minutes on day 1, after completion of docetaxel (75 mg/m2 IV over 1 hour on day 1), every 3 weeks. Premedicate with dexamethasone (8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration) to reduce the incidence and severity of fluid retention and hypersensitivity reactions.[60484] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In a randomized controlled trial, treatment with docetaxel plus cisplatin resulted in a median overall survival of 10.9 months compared with 10 months in patients treated with vinorelbine plus cisplatin.[47583] [60484]

For the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with vinorelbine (EVERY 4 WEEKS)†.
NOTE: Vinorelbine is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage (EVERY 4 WEEKS) Adults

100 mg/m2 IV on day 1 in combination with vinorelbine (25 mg/m2 IV over 6 to 10 minutes on days 1, 8, 15, and 21), every 28 days. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a randomized, multicenter, open-label clinical trial of patients with treatment-naive stage IIIb or stage IV NSCLC, the addition of vinblastine to cisplatin significantly improved median overall survival (7.8 months vs. 6.2 months) and overall response rate (19% vs. 8%) compared to cisplatin alone.

For first-line treatment of inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), in combination with gemcitabine† (EVERY 3 WEEKS).
NOTE: Gemcitabine is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage (EVERY 3 WEEKS) Adults

100 mg/m2 IV on day 1, preceded on day 1 by gemcitabine (1,250 mg/m2 IV over 30 minutes on days 1 and 8), every 21 days. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on the day of therapy. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a multicenter, randomized clinical trial, overall survival was not significantly different for patients with stage IIIB or IV NSCLC treated with gemcitabine/cisplatin (n = 69) compared with etoposide/cisplatin (n = 66) (8.7 months vs. 7 months). The tumor response rate was 33% versus 14%, respectively, with a median time to disease progression of 5 months in the gemcitabine arm and 4.1 months in the etoposide arm.

For first-line treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC), in combination with pemetrexed†.
NOTE: Pemetrexed is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage Adults

75 mg/m2 IV on day 1, preceded by pemetrexed (500 mg/m2 IV over 10 minutes on day 1), every 21 days for 6 cycles or until disease progression or unacceptable toxicity; after the initial dose, monitor the nadir ANC and platelet count to assess for possible pemetrexed dose reductions. To prevent or minimize toxicities, all patients should also receive the following concomitant medications: dexamethasone 4 mg PO twice daily for 3 consecutive days, beginning the day before each pemetrexed dose; folic acid 400 to 1,000 mcg PO daily beginning 7 days prior to the first pemetrexed dose and continuing until 21 days after the last pemetrexed dose; and vitamin B12 injection 1 mg IM one week prior to the first dose of pemetrexed and every 3 cycles (every 9 weeks) thereafter (do not substitute oral vitamin B12 for the IM injection). After the first vitamin B12 injection, subsequent injections may be given on the same day as pemetrexed treatment. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a phase 3 noninferiority trial, 1,725 patients with chemotherapy-naive advanced NSCLC were randomized to receive treatment with either cisplatin/pemetrexed or cisplatin/gemcitabine. No significant differences were observed in either overall survival (10.3 months vs. 10.3 months) or progression-free survival (4.8 months vs. 5.1 months). Analysis of NSCLC histology revealed significantly worse median survival for cisplatin/pemetrexed patients with squamous-cell histology (9.4 months vs. 10.8 months). Grade 3 or 4 neutropenia (27% vs. 15%), anemia (10% vs. 6%), and thrombocytopenia (13% vs. 4%) were all significantly higher in the cisplatin/gemcitabine arm.

For adjuvant treatment of resected non-small cell lung cancer (NSCLC), in combination with vinorelbine†. Intravenous dosage Adults

100 mg/m2 on days 1, 29, 57, and 85 OR 50 mg/m2 on days 1 and 8 repeated every 4 weeks for 16 weeks has been studied in randomized, phase 3 studies.[34316] [34317] Adjuvant therapy with vinorelbine (30 mg/m2 IV once weekly starting on day 1 for up to 16 doses) plus cisplatin (100 mg/m2 on days 1, 29, 57, and 85) led to significantly improved median overall survival (OS) (65.7 months vs. 43.7 months) and disease-free survival (DFS) (36.3 months vs. 20.7 months) compared with surgery +/- radiotherapy alone in a multinational, randomized, phase 3 study in 840 patients with completely resected stage IB to IIIA NSCLC. The absolute OS improvement at 2- and 5-years was 4.7% and 8.4%, respectively. In the adjuvant chemotherapy arm, grade 3 or 4 neutropenia was reported in 85% of patients and there were 7 (2%) treatment-related deaths.[34316] In another randomized, phase 3 study, adjuvant therapy with vinorelbine (25 mg/m2 IV weekly for 16 weeks) plus cisplatin (50 mg/m2 on days 1 and 8 repeated every 4 weeks for 4 cycles) resulted in significantly improved median OS (94 months vs. 73 months) and relapse-free survival (not reached vs. 46.7 months) compared with surgery alone in 482 patients with stage IB or II NSCLC. The absolute improvement in 5-year OS was 11% at a median follow-up time of 9.3 years. In a post-hoc analysis, no OS benefit was observed in patients with stage IB disease. Grade 3 and 4 neutropenia was reported in 73% of patients and there were 2 (0.8%) treatment-related deaths.[34317] [45478] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393]

For the first-line treatment of inoperable, stage II or III non-small cell lung cancer (NSCLC), in combination with vinblastine and radiotherapy†. Intravenous dosage Adults

100 mg/m2 IV on days 1 and 29 in combination with vinblastine 5 mg/m2 IV on days 1, 8, 15, 22, 29 with sequential or concurrent radiotherapy (RT) has been studied in patients with inoperable, stage II or III NSCLC in randomized clinical studies.[44765] [44766] [44767] [44768] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] Median overall survival (OS) times were significantly improved with vinblastine plus cisplatin followed by standard RT (total dose of 60 Gy over 6 weeks) compared with standard RT or hyperfractionated twice daily RT alone in a randomized, phase 3 trial (n = 458) (13.2 months vs. 11.4 and 12 months, respectively).[44765] Additionally, the median OS time was significantly improved with vinblastine plus cisplatin followed by standard RT compared with standard RT alone (13.7 vs. 9.6 months) in a long-term update of a randomized controlled trial in patients with inoperable, stage III NSCLC which was stopped early after an interim analysis (n = 155).[44766] The median OS time was significantly improved when vinblastine plus cisplatin was given concurrently with once daily RT (17 months) compared with vinblastine plus cisplatin followed by standard RT (sequential RT arm) (14.6 months) in another randomized, phase 3 trial presented in abstract form (n = 595).[44767] There was no difference in the median OS time with induction chemotherapy with vinblastine plus cisplatin followed by cisplatin (75 mg/m2 IV on days 50, 71, and 92) and concurrent RT compared with cisplatin (50 mg/m2 IV on days 1 and 8) plus oral etoposide (50 mg twice daily) with concurrent twice daily RT (16.4 vs 15.5 months) in a long-term follow-up analysis of a randomized, phase 2 study (n = 168).[44768]

For adjuvant treatment of resected stage IB to stage III non-small-cell lung cancer (NSCLC), in combination with vinblastine†. Intravenous dosage Adults

80 mg/m2 IV on days 1, 22, 43, and 64 in combination with vinblastine 4 mg/m2 IV on days 1, 8, 15, 22, 29, and 43, then every 14 days until final cisplatin dose. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a phase 3 trial of patients with stage IB to stage III NSCLC (n = 1,867), a significant 4.1% absolute difference in 5-year overall survival (OS) was reported in patients who received cisplatin-based adjuvant chemotherapy (CT) following surgery +/- radiotherapy (RT) compared with surgery +/- RT alone. In subgroup analyses in patients who received cisplatin in combination with a vinca alkaloid, including vinblastine, OS was not significantly different with adjuvant CT compared with surgery +/- RT alone. In a long-term analysis of this study (median follow-up of 7.5 years), OS was no longer significant. Additionally, OS was found to be significantly worse after 5 years in patients who received adjuvant CT.

For the adjuvant treatment of resected stage IB to stage III non-small cell lung cancer (NSCLC), in combination with etoposide†. Intravenous dosage Adults

100 mg/m2 IV on day 1 in combination with etoposide (100 mg/m2 IV on days 1, 2, and 3), every 21 days for 4 cycles. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a phase 3 trial of patients with stage IB to stage III NSCLC (n = 1,867), cisplatin/etoposide was one of several regimens to collectively show an improvement in 5-year survival versus observation (44.5% vs. 40.4%) following complete resection.

For the treatment of stage IIIB non-small cell lung cancer (NSCLC), in combination with etoposide and concurrent radiotherapy†. Intravenous dosage Adults

Induction therapy with 50 mg/m2 IV of cisplatin on days 1, 8, 29, and 36 with etoposide (50 mg/m2 IV on days 1 to 5, and on days 29 to 33) plus concurrent radiotherapy for 25 days starting on day 1 has been studied.  Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Responding patients proceeded to thoracotomy. Median overall survival ranged from 15 to 17 months. Grades 3 or 4 esophagitis and grade 4 neutropenia occurred.

For the first-line treatment of inoperable stage III or IV NSCLC, in combination with mitomycin and vinblastine or ifosfamide†. Intravenous dosage Adults

50 mg/m2 IV cisplatin plus vinblastine 6 mg/m2 IV and mitomycin 6 or 8 mg/m2 IV all given on day 1 and repeated every 3 weeks (MVP regimen) or 50 mg/m2 IV cisplatin plus ifosfamide 3 g/m2 IV and mitomycin 6 mg/m2 IV all given on day 1 and repeated every 3 weeks (MIC regimen) for 4 cycles has been studied in patients with inoperable stage III or IV non-small cell lung cancer (NSCLC) in randomized clinical studies.  Ifosfamide in the MIC regimen should also be administered with mesna to prevent hemorrhagic cystitis (600 mg/m2 IV over 15 minutes before ifosfamide, then 600 mg/m2 IV at 4 and 8 hours from the start of each ifosfamide on day 1). Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. There was no significant difference in the median overall survival (OS) time (8.7 vs 9.5 months), 1-year OS rate (35% vs 39%), or 2-year OS rate (13% vs 13%) in patients who received MVP or MIC compared with docetaxel plus carboplatin (DC regimen) in a multicenter, randomized, phase 3 trial (n = 433). Serious toxicity, including grade 3 and 4 neutropenia and leucopenia, was reported significantly less often in the MVP/MIC arm compared with the DC arm (22% vs 41%); additionally, patients in the MVP/MIC arm had significantly less overnight hospital stays due to toxicity and antibiotic use. In another randomized, phase 3 trial (n = 372), there was no significant difference in the median OS time (248 vs. 236 days), 1-year OS rate (32.5% vs. 33.2%), or 2-year OS rate (11.8% vs. 6.9%) in patients who received MVP or MIC compared with gemcitabine plus carboplatin (GC regimen). Significantly less grade 3 and 4 neutropenia and thrombocytopenia and antibiotic use were reported with MVP/MIC compared with GC; however, emergent overnight hospital stays occurred significantly more often in the MVP/MIC arm.

For the first-line treatment of advanced non-small cell lung cancer (NSCLC), in combination with vinorelbine and cetuximab†. Intravenous dosage Adults

80 mg/m2 IV on day 1 in combination with vinorelbine (25 mg/m2 IV on days 1 and 8) every 21 days, and weekly cetuximab (400 mg/m2 IV the first week with subsequent weekly infusions of 250 mg/m2 IV). Cisplatin and vinorelbine are given up to 6 cycles. Weekly cetuximab should continue until unacceptable toxicity or disease progression. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a phase 3 trial of patients with advanced EGFR-detectable NSCLC (n = 1,125), the addition of cetuximab to cisplatin/vinorelbine significantly improved the primary endpoint overall survival (11.3 months vs. 10.1 months). Response rate (36% vs. 29%) and time to treatment failure (4.2 months vs. 3.7 months) were also significantly greater in the cetuximab arm. Patients who received cetuximab had a significantly higher incidence of febrile neutropenia (22% vs. 15%). Multiple previous trials of EGFR-targeted tyrosine kinase inhibitors in combination with chemotherapy in the front-line treatment of patients with non-small cell lung cancer have generally shown no additional survival benefit with the addition of the tyrosine kinase inhibitor. Consideration should be given to the use of molecular markers to aid in patient selection as further information about this practice continues to become available.

For the treatment of advanced non-small cell lung cancer (NSCLC), in combination with irinotecan†. Intravenous dosage Adults

80 mg/m2 IV on day 1 in combination with irinotecan 60 mg/m2 IV over 90 minutes on days 1, 8, and 15, repeated every 4 weeks. Alternatively, a regimen of cisplatin 30 mg/m2 IV then irinotecan 65 mg/m2 IV over 90 minutes (50 mg/m2 IV for previously treated patients) administered weekly for 4 weeks followed by a 2 week rest has been studied. Treatment was continued for a maximum of 6 cycles. Overall survival is similar to other platinum-based doublets.] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with vinorelbine (EVERY 6 WEEKS)†.
NOTE: Vinorelbine is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage (EVERY 6 WEEKS) Adults

120 mg/m2 IV on days 1 and 29, then every 6 weeks, in combination with vinorelbine (30 mg/m2 IV over 6 to 10 minutes once weekly). Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.In a randomized, multicenter, open-label clinical trial of treatment-naive stage III or IV NSCLC, median overall survival was significantly improved in patients treated with vinorelbine plus cisplatin (n = 206) compared with vindesine plus cisplatin (n = 200) (9.2 months vs. 7.4 months); overall survival was also improved compared with vinorelbine alone (n = 206) (7.2 months). Treatment with vinorelbine/cisplatin also significantly improved overall response compared with vinorelbine/cisplatin and vinorelbine (28% vs. 19% vs. 14%).

For the first-line treatment of inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), in combination with gemcitabine† (EVERY 4 WEEKS).
NOTE: Gemcitabine is FDA-approved in combination with cisplatin for this indication.
Intravenous dosage (EVERY 4 WEEKS) Adults

100 mg/m2 IV on day 1, preceded on day 1 by gemcitabine (1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15), every 28 days. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on the day of therapy. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In a multicenter, randomized clinical trial, first-line treatment with gemcitabine cisplatin (n = 260) significantly improved overall survival compared with cisplatin alone (n = 262) in patients with inoperable stage IIIA, IIIB, or IV NSCLC (9 months vs. 7.6 months). The tumor response rate (26% vs. 10%) and time to disease progression (5.2 months vs. 3.7 months) were also significantly improved in the gemcitabine arm.

For the first-line treatment of metastatic, EGFR- and ALK-negative, nonsquamous NSCLC, in combination with pemetrexed and pembrolizumab†.
NOTE: Pembrolizumab is FDA-approved in combination with both pemetrexed and cisplatin for this indication.
Intravenous dosage Adults

75 mg/m2 IV on day 1 and pemetrexed (500 mg/m2 IV on day 1) repeated every 21 days for 4 cycles in combination with pembrolizumab (200 mg IV on day 1 every 3 weeks OR 400 mg IV on day 1 every 6 weeks). Administer pembrolizumab first, followed pemetrexed, followed by cisplatin. After the initial dose, monitor the nadir ANC and platelet count to assess for possible pemetrexed dose reductions. Followin

g completion of platinum-based therapy, pembrolizumab may be continued as maintenance therapy for up to 24 months, either alone or in combination with pemetrexed, until disease progression or unacceptable toxicity. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In a multicenter double-blind clinical trial (KEYNOTE-189), patients with previously untreated metastatic, EGFR- and ALK-negative, nonsquamous NSCLC, regardless of PD-L1 status, were randomized to treatment with pemetrexed plus either cisplatin or carboplatin, in combination with either pembrolizumab (n = 410) or placebo (n = 206). After a median follow-up of 31 months, the median overall survival (22 months vs. 10.6 months), progression-free survival (9 months vs. 4.9 months), and overall response rate (48.3% vs. 19.9%) were significantly improved in the pembrolizumab arm. The median duration of response was 12.5 months for patients who received pembrolizumab plus pemetrexed/platinum chemotherapy compared with 7.1 months in those receiving placebo plus pemetrexed/platinum chemotherapy.[57889] [28376]

For the first-line treatment of metastatic malignant melanoma† in combination with vinblastine and dacarbazine. Intravenous dosage Adults

20 mg/m2/day IV over 30 minutes on days 1, 2, 3, 4 in combination with vinblastine 1.2 mg/m2/day IV on days 1, 2, 3, 4 and dacarbazine 800 mg/m2 IV over 1 hour on day 1, repeated every 21 days (CVD regimen) for up to 4 cycles.

For the treatment of localized and unresectable neuroblastoma† in combination with etoposide, alternating with cyclophosphamide, vincristine, and doxorubicin. Intravenous dosage Adolescents and Children

40 mg/m2/day IV on days 1, 2, 3, 4, 5 in combination with etoposide 100 mg/m2/day IV on days 1, 2, 3, 4, 5 (CVP regimen), alternating with cyclophosphamide, vincristine, and doxorubicin (CADO regimen). Two cycles of each regimen should be given as induction therapy, followed by surgery. The administration of cisplatin as a 1-hour infusion reduced the incidence of neutropenia compared to administration as a continuous infusion.

For the treatment of penile cancer†. For the treatment of locally advanced or metastatic penile cancer in combination with methotrexate and bleomycin†. Intravenous dosage Adults

75 mg/m2 IV on day 1 in combination with methotrexate 25 mg/m2 IV bolus on days 1 and 8 and bleomycin 10 units/m2 IV on days 1 and 8, repeated every 21 days. Treatment was given for 6 cycles if a complete remission was achieved. Patients who achieved stable disease or partial response continued treatment until disease progression. Bleomycin was discontinued after a maximum cumulative dose of 200 units/m2 was given.[47056] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the neoadjuvant treatment of locally advanced or metastatic carcinoma of the penis in combination with paclitaxel and ifosfamide†. Intravenous dosage Adults

25 mg/m2 per day IV over 2 hours on days 1 to 3 in combination with paclitaxel (175 mg/m2 IV over 3 hours on day 1) and ifosfamide (1,200 mg/m2 per day IV over 2 hours on days 1 to 3), repeated every 3 to 4 weeks.[51058] Mesna (240 mg/m2 IV over 15 minutes before ifosfamide, then 240 mg/m2 IV at 4 and 8 hours from the start of each ifosfamide on days 1 to 3) should be administered with ifosfamide to prevent hemorrhagic cystitis.[51027] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393]

For the treatment of head and neck cancer†. For the treatment of advanced or recurrent head and neck cancer in combination with fluorouracil†. Intravenous dosage Adults

100 mg/m2 IV on day 1 in combination with fluorouracil (1,000 mg/m2 per day continuous IV infusion on days 1, 2, 3, and 4), repeated every 3 weeks has been studied. No difference in overall survival was seen when compared to cisplatin and paclitaxel.

For the treatment of previously untreated resectable squamous cell head and neck cancer of the larynx†. Intravenous dosage Adults

100 mg/m2 IV on days 1, 22, and 43 during radiation therapy (70 Gy; delivered in 35 fractions over 7 weeks). In a phase 3 trial of 547 patients, cisplatin/radiation resulted in a significantly higher percentage of patients with an intact larynx at 3.8 years median follow-up compared to induction cisplatin/fluorouracil followed by radiation (88% vs. 75%), or radiation alone (88% vs. 70%). Overall survival was not significantly different between the treatment groups. Toxicity was increased in each of the chemotherapy arms; mucosal toxicity was significantly worse in the cisplatin/radiation arm.

For the treatment of previously untreated unresectable squamous cell head and neck cancer, excluding cancers of the nasopharynx, paranasal sinus, or parotid gland†. Intravenous dosage Adults

100 mg/m2 IV on days 1, 22, and 43 during radiation therapy (XRT) (70 Gy; delivered in 35 fractions over 7 weeks). In a phase 3 trial of 295 patients, cisplatin/XRT was compared to XRT alone and a split course of cisplatin/5-FU with XRT. Overall survival at 3 years was significantly higher in the cisplatin/XRT arm compared to XRT alone (37% vs. 23%). Cisplatin/5-FU with XRT was not significantly different than XRT alone.

For the treatment of previously untreated squamous cell head and neck cancer of the oral cavity, oropharynx, hypopharynx, or larynx†. Intravenous dosage Adults

100 mg/m2 IV on days 1, 22, and 43 during radiation therapy (XRT) has been studied. In a phase 3 trial of 334 patients, cisplatin/XRT significantly improved progression-free survival, the primary endpoint, compared to XRT alone at a median follow-up of 60 months (HR 0.75). Overall survival was also significantly longer in the combination therapy arm (HR 0.7). The incidence of grade 3 and 4 adverse events was significantly higher with combination therapy compared with XRT alone (41% vs. 21%). In another phase 3 trial, 459 patients with high-risk squamous cell carcinoma of the head and neck were randomized to receive adjuvant cisplatin/XRT or XRT alone. Local and regional tumor control, the primary endpoint, was significantly improved in the combination therapy arm (HR 0.61). Disease-free survival was also significantly improved in the combination therapy arm (HR, 0.78), but overall survival was similar. The incidence of grade 3 and 4 adverse events was significantly higher with combination therapy compared with XRT alone (77% vs. 34%).

For the treatment of advanced nasopharyngeal head and neck cancer in combination with fluorouracil and radiotherapy†. Intravenous dosage Adults

100 mg/m2 IV over 15 to 20 minutes on days 1, 22, and 43 concurrently with radiation therapy (RT) followed by cisplatin 80 mg/m2 IV on days 71, 99, and 127 in combination with 5-fluorouracil (1,000 mg/m2 per day IV over 4 days on days 71 to 74, 99 to 102, and 127 to 130). In a phase 3 trial of 147 patients with advanced nasopharyngeal cancer, chemoradiotherapy significantly improved 3-year progression-free survival (69% vs. 24%) and overall survival (76% vs. 46%) rates compared with RT alone.

For induction treatment of inoperable, locally advanced squamous cell head and neck cancer in combination with docetaxel and fluorouracil, followed by radiotherapy†.
NOTE: Docetaxel is FDA-approved in combination with cisplatin and fluorouracil for this indication.
Intravenous dosage Adults

75 mg/m2 IV over 1 hour on day 1, administered after docetaxel (75 mg/m2 IV over 1 hour on day 1) and followed by fluorouracil 750 mg/m2 per day by continuous IV infusion on days 1 to 5, repeated every 3 weeks for 4 cycles. Beginning 1 day prior to docetaxel administration, premedicate with dexamethasone 8 mg by mouth twice daily for 3 days to reduce the incidence and severity of fluid retention and hypersensitivity reactions. After completion of chemotherapy, patients should receive radiation therapy. In clinical trials, colony-stimulating factors were recommended during the second and/or subsequent cycles in case of febrile neutropenia, documented infection with neutropenia, or neutropenia lasting more than 7 days. Treatment with cisplatin, docetaxel, and fluorouracil followed by radiotherapy significantly improved median progression-free survival (11.4 months vs. 8.3 months) and median overall survival (18.6 months vs. 14.2 months) compared with cisplatin and fluorouracil, without docetaxel, in patients with inoperable, locally advanced squamous cell head and neck cancer in a randomized, open-label trial (TAX323).

For induction treatment of locally advanced (unresectable, low surgical cure, or organ preservation) squamous cell head and neck cancer in combination with docetaxel and fluorouracil, followed by chemoradiotherapy†.
NOTE: Docetaxel FDA-approved in combination with cisplatin and fluorouracil for this indication.
Intravenous dosage Adults

100 mg/m2 IV over 30 minutes to 3 hours on day 1, administered after docetaxel (75 mg/m2 IV over 1 hour on day 1) and followed by fluorouracil 1,000 mg/m2 per day by continuous IV infusion on days 1 to 4, repeated every 3 weeks for 3 cycles. Beginning 1 day prior to docetaxel administration, premedicate with dexamethasone 8 mg by mouth twice daily for 3 days to reduce the incidence and severity of fluid retention and hypersensitivity reactions. After completion of chemotherapy, patients should receive radiation therapy with concurrent carboplatin (AUC 1.5 IV over 1 hour once weekly for up to 7 doses). Treatment with cisplatin, docetaxel, and fluorouracil followed by chemoradiotherapy significantly improved median overall survival (70.6 months vs. 30.1 months) compared with cisplatin and fluorouracil, without docetaxel, in patients with locally advanced (unresectable, low surgical cure, or organ preservation) squamous cell head and neck cancer in a randomized, open-label clinical trial (TAX324).

For the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck in combination with cetuximab†. Intravenous dosage Adults

100 mg/m2 IV on day 1 in combination with cetuximab (400 mg/m2 IV over 120 minutes on day 1, then 250 mg/m2 IV over 60 minutes weekly from day 8); the treatment regimen was repeated every 4 weeks until disease progression or for 2 treatment cycles after the achievement of a complete response. Treatment with cetuximab and cisplatin significantly improved the objective response rate (26% vs. 10%) in patients with recurrent or metastatic head and neck cancer compared with cisplatin monotherapy in a phase 3 clinical trial; however, neither the primary endpoint of progression-free survival (4.2 months vs. 2.7 months) nor overall survival (9.2 months vs. 8 months) were significantly improved in the cetuximab arm.[32012]

For the first-line treatment of recurrent locoregional or metastatic squamous cell carcinoma of the head and neck in combination with cetuximab and fluorouracil†.
NOTE: Cetuximab is FDA-approved in combination with cisplatin and fluorouracil for this indication.
Intravenous dosage Adults

100 mg/m2 IV on day 1, in combination with fluorouracil (1,000 mg/m2 per day IV infusion over days 1 to 4), every 3 weeks for up to 6 cycles. Administer with cetuximab (400 mg/m2 IV as an initial loading dose on day 1 followed by weekly infusions of cetuximab 250 mg/m2 IV; alternatively, cetuximab may be administered at a dose of 500 mg/m2 IV every 2 weeks). Complete cetuximab administration 1 hour prior to chemotherapy and continue until disease progression or unacceptable toxicity. In a phase 3 trial, 442 patients were randomized to receive cisplatin or carboplatin and fluorouracil, with or without cetuximab, for 6 cycles. Overall survival, the primary endpoint, was significantly greater with the addition of cetuximab to chemotherapy compared with chemotherapy alone (10.1 months vs. 7.4 months). However, sepsis, hypomagnesemia, grade 3 skin reactions, and grade 3 or 4 infusion reactions also occurred more frequently with the addition of cetuximab.[35055] [51181]

For the treatment of anal cancer in combination with 5-fluorouracil and radiation therapy†. Intravenous dosage Adults

Multiple dosage regimens have been studied. Cisplatin 100 mg/m2 IV on day 1 in combination with 5-fluorouracil (5-FU) (750 mg/m2/day continuous IV infusion on days 1—4), repeated every 21 days for 2—3 cycles has been given with concomitant radiation (XRT). Alternately, cisplatin 75 mg/m2 IV over 60 minutes on day 1 has been given in combination with 5-FU 1000 mg/m2/day as a CIVI on days 1—4, repeated every 28 days for 4 cycles.

For the treatment of biliary tract cancer† in combination with gemcitabine. Intravenous dosage Adults

25 mg/m2 IV on days 1 and 8 in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8) every 21 days for 8 cycles.[40363] [35538] [40365] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393] In a phase 3 trial, 410 patients with advanced cholangiocarcinoma, gallbladder cancer, or ampullary cancer were randomized to receive gemcitabine with or without cisplatin. Overall survival, the primary endpoint, was significantly greater in the combination treatment arm (11.7 months vs. 8.1 months). Median progression-free survival was also significantly greater in the combination treatment arm (8 months vs. 5 months). Grade 3 or 4 neutropenia (25.3% vs. 16.6%) and anemia (7.6% vs. 3%) occurred more frequently with combination therapy. The overall incidence of grade 3 or 4 toxicities was not significantly different between the 2 treatment arms (70.7% vs. 68.8%).[40363] [35538] [40365] Additional trials have shown a benefit for gemcitabine/cisplatin compared to cisplatin alone.[40364]

For the treatment of hepatocellular cancer†. For the treatment of advanced stage hepatocellular carcinoma in combination with doxorubicin†. Hepatic arterial infusion dosage Adults

100 mg/m2 in combination with doxorubicin 30 mg/m2, has been administered via intra-arterial administration in the hepatic artery, as a solution or emulsified with the use of Lipiodol. Treatment was repeated every 2 months for at least 3 cycles.

For the treatment of advanced hepatocellular carcinoma†. Intravenous dosage Adults

Dosage not established. 90 mg/m2 IV once every 21 days or 80 mg/m2 IV once every 28 days.

For the treatment of unresectable, advanced thymoma†. For unresectable, advanced thymoma in combination with cyclophosphamide and doxorubicin†. Intravenous dosage Adults

50 mg/m2 IV plus doxorubicin (50 mg/m2 IV) and cyclophosphamide (500 mg/m2 IV with 1 liter hydration before and after chemotherapy) on day 1, every 21 days (PAC regimen) for up to 8 cycles in patients with previously untreated, unresectable, extensive-stage thymoma or for 2 or 4 cycles followed by radiotherapy in patients with previously untreated, unresectable, limited-stage thymoma who had stable disease or better have been evaluated in nonrandomized studies. Additionally, multimodality treatment with 3 cycles of cisplatin 30 mg/m2 per day IV on days 1 to 3, doxorubicin 30 mg/m2 per day continuous IV infusion over 24 hours on days 1 to 3, cyclophosphamide 500 mg/m2 IV on day 1, and prednisone 100 mg PO on days 1 to 5, repeated every 3 to 4 weeks followed by surgery and radiation therapy and then consolidation chemotherapy with cisplatin, doxorubicin, and cyclophosphamide given at 80% of the original doses and prednisone (given at 100%) repeated every 3 to 4 weeks for 3 cycles has also been evaluated in another nonrandomized study. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. In these studies, overall response rates and overall survival rates were favorable.

For unresectable, advanced thymoma in combination with cyclophosphamide, doxorubicin, and vincristine†. Intravenous dosage Adults

50 mg/m2 IV on day 1 plus doxorubicin (40 mg/m2 IV on day 1), vincristine (0.6 mg/m2 IV on day 3), and cyclophosphamide (700 mg/m2 IV on day 4), every 3 weeks resulted in a favorable overall response rate in a nonrandomized study of 37 patients. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For unresectable, advanced thymoma in combination with etoposide and ifosfamide†. Intravenous dosage Adults

20 mg/m2 (with hydration) plus ifosfamide (1,200 mg/m2 IV), mesna (240 mg/m2 IV push prior to and at 4 and 8 hours after each ifosfamide dose), and etoposide (75 mg/m2 IV) on days 1 to 4, every 3 weeks for 4 cycles or until disease progression or unacceptable toxicity. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Treatment with cisplatin, ifosfamide, mesna, and etoposide resulted in favorable overall response rates in a nonrandomized study of 28 patients (20 with thymoma). All patients received granulocyte colony-stimulating factor 5 mcg/kg per day subcutaneously on days 5 to 15 or until a post-nadir white blood cell count of 10,000 cells/mm3.

For unresectable, advanced thymoma in combination with etoposide†. Intravenous dosage Adults

60 mg/m2 IV over 1 hour (with hydration) on day 1 plus etoposide (120 mg/m2 IV over at least 30 minutes on days 1 to 3), every 3 weeks for up to 8 cycles has been studied in 16 patients in a phase 2 study. The overall response rate was 56%.[41519] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.[28393]

For the first-line treatment of unresectable, advanced thymic carcinoma†, in combination with etoposide and ifosfamide. Intravenous dosage Adults

20 mg/m2/day IV (with hydration) on days 1, 2, 3, 4 plus ifosfamide 1200 mg/m2/day IV (with mesna 240 mg/m2 IV push prior to and at 4 and 8 hours after each ifosfamide dose) on days 1, 2, 3, 4 and etoposide 75 mg/m2/day IV on days 1, 2, 3, 4 repeated every 3 weeks for 4 cycles or until disease progression or unacceptable toxicity (median of 4 cycles; range, 1 to 6 cycles) resulted in an overall response rate (ORR) of 32% (all partial responses; median duration of response, 11.9 months) in 28 patients with advanced thymoma or thymic carcinoma in a nonrandomized study. All patients received granulocyte colony-stimulating factor 5 mcg/kg/day subcutaneously on days 5 through 15 or until a postnadir white blood cell count of 10,000/mm3. At a median follow-up of 43 months, the median overall survival (OS) time was 31.6 months and the 1- and 2-year OS rates were 89% and 70%, respectively. In the 8 patients with advanced thymic carcinoma, the ORR was 25% and the 1- and 2-year OS rates were 75% and 50%, respectively. Serious toxicity reported in this study included grade 3 or 4 thrombocytopenia (18%), leukopenia (16%), and anemia (15%).

For the treatment of peripheral T-cell lymphoma (PTCL)†. For the first-line treatment of PTCL in combination with gemcitabine, prednisone, and thalidomide†. Intravenous dosage Adults and Adolescents 14 years and older

25 mg/m2 IV on days 1, 2, and 3 in combination with gemcitabine (800 mg/m2 IV over 30 minutes on days 1 and 8), prednisone (60 mg/m2 PO on days 1, 2, 3, 4, and 5), and thalidomide (200 mg PO daily) repeated every 21 days until disease progression or for up to 6 cycles was evaluated in patients with previously untreated PTCL in a randomized trial. Patients received aspirin 100 mg/day PO during thalidomide therapy. The use of granulocyte colony-stimulation factor was permitted as indicated. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration.

For the treatment of small cell lung cancer (SCLC)†. For the first-line treatment of extensive-stage small cell lung cancer (SCLC), in combination with etoposide and durvalumab.
NOTE: Durvalumab is FDA-approved in combination with cisplatin and etoposide for this indication.
Intravenous dosage Adults weighing more than 30 kg

75 to 80 mg/m2 IV on day 1 plus etoposide (80 to 100 mg/m2 IV on days 1 to 3), following administration of durvalumab (1,500 mg IV over 60 minutes on day 1), every 3 weeks for 4 cycles; administer durvalumab prior to chemotherapy when given on the same day.  Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. After completion of 4 cycles of durvalumab plus chemotherapy, continue durvalumab 1,500 mg IV every 4 weeks as a single agent until disease progression or unacceptable toxicity. Durvalumab significantly improved overall survival by approximately 3 months when added to platinum-etoposide chemotherapy compared with platinum-etoposide alone in patients with extensive-stage SCLC in a randomized clinical trial.

Adults weighing 30 kg or less

75 to 80 mg/m2 IV on day 1 plus etoposide (80 to 100 mg/m2 IV on days 1 to 3), following administration of durvalumab (20 mg/kg IV over 60 minutes on day 1), every 3 weeks for 4 cycles; administer durvalumab prior to chemotherapy when given on the same day.  Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. After completion of 4 cycles of durvalumab plus chemotherapy, continue durvalumab 20 mg/kg IV every 4 weeks as a single agent until disease progression or unacceptable toxicity. Durvalumab significantly improved overall survival by approximately 3 months when added to platinum-etoposide chemotherapy compared with platinum-etoposide alone in patients with extensive-stage SCLC in a randomized clinical trial.

For the treatment of urothelial carcinoma†. For the first-line treatment of locally advanced or metastatic urothelial carcinoma, in combination with gemcitabine and atezolizumab†. Intravenous dosage Adults

70 mg/m2 IV on day 1, in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8) and atezolizumab (1,200 mg IV over 60 minutes on day 1), every 21 days for up to 6 cycles. In a randomized phase 3 trial (the IMvigor 130 trial), the addition of atezolizumab to platinum-based chemotherapy in patients with metastatic urothelial cancer significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy alone in the intent-to-treat population; the PFS benefit in the atezolizumab arm was seen across all subgroups, although it was not statistically significant in several including patients with PD-L1 0/1 expression and in patients receiving carboplatin- versus cisplatin-based regimens. At an interim analysis after 11.8 months of follow-up, overall survival was not significantly different between groups.

For the adjuvant treatment of locally advanced urothelial cancer of the upper urinary tract (UTUC), in combination with gemcitabine†. Intravenous dosage Adults

70 mg/m2 IV over 4 hours on day 1 in combination with gemcitabine (1,000 mg/m2 IV over 30 minutes on day 1 and 8), every 21 days for 4 cycles. The cisplatin dose may be divided over 2 consecutive days for patients with baseline CrCl of 70 mL/min or higher that falls to 50 to 69 mL/min during treatment. Substitute carboplatin (AUC 4.5 or 5 IV over 1 hour) for cisplatin in patients with impaired renal function (CrCl 30 go 49 mL/min). In a randomized, phase 3 clinical trial, treatment with gemcitabine plus either cisplatin or carboplatin significantly improved disease-free survival in patients with locally advanced UTUC when initiated within 90 days after radical nephroureterectomy compared with surveillance. Based on recommendations from the independent data monitoring committee, study enrollment was ended early and patients still within the 90-day window from nephroureterectomy were offered chemotherapy.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

No dosage adjustments are needed in patients with hepatic impairment.

Renal Impairment

No specific dosage guidelines have been established for cisplatin in patients with renal impairment, although the manufacturer recommends considering alternative treatments or reducing the dose of cisplatin for patients with baseline renal impairment or who develop significant treatment-related reactions in creatinine clearance (CrCL).[28393] The following recommendations have been made in the literature:
 
Kintzel, et al.:[25912]
CrCL 46 to 60 mL/min: Reduce cisplatin dose by 25%.
CrCL 31 to 45 mL/min: Reduce cisplatin dose by 50%.
CrCL 30 mL/min or less: Not recommended.
 
Pedrazzoli, et al.:[64123]
Hemodialysis: Reduce cisplatin dose by 50% to 75%; administer after hemodialysis.

Drug Interactions

Acyclovir: (Moderate) Closely monitor renal function if concomitant use with cisplatin and acyclovir is necessary. Cisplatin can cause nephrotoxicity. Acyclovir can cause renal impairment or renal failure, which may be additive when used with cisplatin.
Adefovir: (Moderate) Closely monitor renal function if concomitant use with cisplatin and adefovir is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Amikacin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Aminoglycosides: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Amphotericin B lipid complex (ABLC): (Moderate) Closely monitor renal function if concomitant use with cisplatin and amphotericin B is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Amphotericin B liposomal (LAmB): (Moderate) Closely monitor renal function if concomitant use with cisplatin and amphotericin B is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Amphotericin B: (Moderate) Closely monitor renal function if concomitant use with cisplatin and amphotericin B is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Aprotinin: (Moderate) Carefully consider the benefits versus risks of concomitant treatment with aprotinin (bovine) and cisplatin. Closely monitor renal function if concurrent use is necessary. Aprotinin increases the risk for renal dysfunction and may increase the need for dialysis in the perioperative period. Cisplatin can cause nephrotoxicity, which may be additive with other agents causing renal impairment.
Arsenic Trioxide: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia such as cisplatin. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms. Additionally, closely monitor renal function if concomitant use is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Bacitracin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and bacitracin is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Bleomycin: (Moderate) Monitor for an increase in bleomycin-related adverse reactions if coadministration with cisplatin is necessary. Bleomycin is primarily eliminated through renal excretion; therefore, its clearance may be affected by nephrotoxic agents such as cisplatin. In one report of 2 children receiving concomitant cisplatin with bleomycin, total body clearance of bleomycin decreased from 39 mL/min/m2 to 18 mL/min/m2 as the cumulative dose of cisplatin exceeded 300 mg/m2; the terminal half-life of bleomycin also increased from 4.4 hours to 6 hours. Fatal bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.
Bumetanide: (Major) Avoid coadministration of bumetanide and cisplatin due to the risk of additive ototoxicity and nephrotoxicity. Both drugs can cause ototoxicity and nephrotoxicity; there has been no experience with the concurrent use of bumetanide and other nephrotoxic agents.
Capreomycin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and capreomycin is necessary. Both cisplatin and capreomycin can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Carbamazepine: (Moderate) Cisplatin may increase the rate of carbamazepine metabolism via CYP3A4 induction. Monitor the serum carbamazepine concentration if cisplatin is used concurrently. The carbamazepine dose may need to be increased.
Cetuximab: (Major) Cetuximab is not indicated for the treatment of squamous cell cancer of the head and neck (SCCHN) in combination with radiation and cisplatin due to the risk of increased serious adverse reactions. In a controlled study of patients with locally advanced SCCHN (n = 940), treatment with cetuximab in combination with radiation therapy and cisplatin increased the incidence of grade 3 and 4 mucositis, radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances compared to radiation and cisplatin alone. Myocardial ischemia occurred in 2% of patients in the cetuximab arm compared with 0.9% in the control arm; adverse reactions with fatal outcome were reported in 4% in the cetuximab arm and 3% in the control arm. The addition of cetuximab to radiation and cisplatin did not improve progression free survival.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cidofovir: (Major) Discontinue cisplatin at least 7 days prior to beginning cidofovir. Closely monitor renal function if concomitant use with cisplatin and cidofovir is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Cisapride: (Major) Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias. Cisplatin can cause hypomagnesemia, hypocalcemia, hyponatremia and impaired renal function. Cisapride is contraindicated for use in patients with known serum electrolyte imbalances; cisapride should be discontinued if such imbalances occur.
Clindamycin: (Moderate) Concomitant use of cisplatin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Colistimethate, Colistin, Polymyxin E: (Major) Colistimethate sodium should be used cautiously in patients receiving cisplatin. Other nephrotoxic drugs can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. Assessment of serum creatinine, blood urea nitrogen, creatinine clearance, magnesium, sodium, potassium, and calcium concentrations before the initial and each subsequent treatment course is recommended.
Colistin: (Major) Colistimethate sodium should be used cautiously in patients receiving cisplatin. Other nephrotoxic drugs can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. Assessment of serum creatinine, blood urea nitrogen, creatinine clearance, magnesium, sodium, potassium, and calcium concentrations before the initial and each subsequent treatment course is recommended.
Cyclosporine: (Moderate) Closely monitor renal function if concomitant use with cisplatin and cyclosporine is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Desmopressin: (Moderate) Frequently monitor serum sodium levels if concurrent use of desmopressin and cisplatin is necessary. Cisplatin can cause hyponatremia, which may increase the risk of water intoxication in patients receiving treatment with desmopressin.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Droperidol: (Moderate) Monitor electrolytes if concurrent use of droperidol and cisplatin is necessary. Cisplatin can cause hypokalemia and hypomagnesemia, which may precipitate QT prolongation. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Entecavir: (Moderate) Closely monitor for entecavir-related adverse reactions if coadministration with cisplatin is necessary. Entecavir is primarily eliminated by the kidneys and cisplatin can cause nephrotoxicity; entecavir concentrations may be increased. The effects of coadministration of entecavir with drugs that are known to affect renal function have not been evaluated.
Ethacrynic Acid: (Major) Avoid coadministration of ethacrynic acid and cisplatin due to the risk of additive ototoxicity.
Foscarnet: (Moderate) Closely monitor renal function if concomitant use with cisplatin and foscarnet is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Fosphenytoin: (Moderate) Closely monitor phenytoin concentrations if coadministration of fosphenytoin with cisplatin is necessary, as cisplatin may decrease phenytoin levels. The addition or withdrawal of cisplatin in patients already on fosphenytoin therapy may require an adjustment of the fosphenytoin dose to achieve optimal clinical outcome.
Furosemide: (Moderate) Closely monitor renal function and audiometric testing if concomitant use of cisplatin and furosemide is necessary. Both cisplatin and furosemide can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Gadobenate Dimeglumine: (Moderate) Monitor for an increase in cisplatin-related adverse reactions if coadministration with gadobenate dimeglumine is necessary. Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as cisplatin, may result in prolonged systemic exposure of the coadministered drug.
Ganciclovir: (Moderate) Concomitant use of cisplatin and ganciclovir should be considered only if the potential benefits outweigh the risks of increased treatment-related toxicities. If coadministration is necessary, closely monitor for treatment-related adverse reactions. Ganciclovir is eliminated renally and cisplatin can cause nephrotoxicity, which may result in increased plasma concentrations of ganciclovir. Side effects such as nephrotoxicity and myelosuppression may be additive.
Gentamicin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and immune globulin products (IVIG) are necessary. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Cisplatin can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins. IVIG has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death.
Ifosfamide: (Moderate) Closely monitor renal function if concomitant use with cisplatin and ifosfamide is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Immune Globulin IV, IVIG, IGIV: (Moderate) Closely monitor renal function if concomitant use with cisplatin and immune globulin products (IVIG) are necessary. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Cisplatin can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins. IVIG has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and cisplatin due to the risk of glomerulonephritis and nephrotoxicity.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Lithium: (Moderate) Closely monitor renal function, and monitor for signs and symptoms of lithium toxicity if coadministration with cisplatin is necessary. Cisplatin can cause nephrotoxicity. Lithium is renally eliminated; concomitant use of drugs that affect kidney function can increase lithium serum concentrations.
Live Vaccines: (Contraindicated) Do not administer live vaccines to cisplatin recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving cisplatin. At least 2 weeks before initiation of cisplatin therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Cisplatin recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Mannitol: (Major) Avoid use of mannitol and cisplatin, if possible. Concomitant administration of nephrotoxic drugs, such as cisplatin, increases the risk of renal failure after administration of mannitol.
Melphalan Flufenamide: (Moderate) Concomitant use of melphalan and cisplatin may result in increased melphalan levels. Cisplatin induced-renal dysfunction may alter the clearance of melphalan. Melphalan clearance is decreased in patients with renal impairment.
Melphalan: (Moderate) Concomitant use of melphalan and cisplatin may result in increased melphalan levels. Cisplatin induced-renal dysfunction may alter the clearance of melphalan. Melphalan clearance is decreased in patients with renal impairment.
Methotrexate: (Moderate) Closely monitor renal function and watch for methotrexate-related adverse reactions if concomitant use of cisplatin and methotrexate is necessary. Cisplatin and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with cisplatin may result in decreased renal function as well as increased methotrexate plasma concentrations.
Neomycin: (Major) Avoid the concurrent and/or sequential use of systemic neomycin with cisplatin due to the risk of additive nephrotoxicity and ototoxicity. Both drugs can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Non-Ionic Contrast Media: (Moderate) Closely monitor renal function if concomitant use with cisplatin and non-ionic contrast media is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Paromomycin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Pentamidine: (Major) Avoid the concomitant or sequential use of intravenous pentamidine with cisplatin if possible due to the risk of additive nephrotoxicity. Cisplatin can cause nephrotoxicity. Nephrotoxic events (increased creatinine, impaired renal function, azotemia, and renal failure) are common with the parenteral administration of pentamidine.
Phenytoin: (Moderate) Closely monitor phenytoin concentrations if coadministration with cisplatin is necessary, as cisplatin may decrease phenytoin levels. The addition or withdrawal of cisplatin in patients already on phenytoin therapy may require an adjustment of the phenytoin dose to achieve optimal clinical outcome.
Plazomicin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Polymyxin B: (Major) Avoid the concurrent or sequential use of polymyxin B with cisplatin due to the risk of additive nephrotoxicity. Cisplatin can cause nephrotoxicity. In therapeutic doses, polymyxin B also causes nephrotoxicity with tubule damage.
Rituximab: (Moderate) Closely monitor renal function for signs of renal failure if concomitant use with cisplatin and rituximab is necessary; discontinue rituximab in patients with a rising serum creatinine or oliguria. The combination of cisplatin and rituximab is not an approved treatment regimen. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with non-Hodgkin's Lymphoma administered concomitant cisplatin therapy during clinical trials.
Rituximab; Hyaluronidase: (Moderate) Closely monitor renal function for signs of renal failure if concomitant use with cisplatin and rituximab is necessary; discontinue rituximab in patients with a rising serum creatinine or oliguria. The combination of cisplatin and rituximab is not an approved treatment regimen. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with non-Hodgkin's Lymphoma administered concomitant cisplatin therapy during clinical trials.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Streptomycin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Streptozocin: (Moderate) Other nephrotoxic drugs, such as streptozocin, can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy.
Tacrolimus: (Moderate) Closely monitor renal function and tacrolimus concentrations if concomitant use with cisplatin and tacrolimus is necessary; adjust the dose of tacrolimus if necessary. Both cisplatin and tacrolimus can cause nephrotoxicity, which may be additive.
Telavancin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and telavancin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cisplatin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Major) Avoid tenofovir administration with concurrent or recent treatment with cisplatin. Cisplatin can cause nephrotoxicity. Tenofovir is primarily eliminated by the kidneys; drugs that decrease renal function may increase concentrations of tenofovir. Also, cases of acute renal failure after initiation of other nephrotoxic drugs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir treatment; some patients required hospitalization and renal replacement therapy.
Thalidomide: (Moderate) Monitor for peripheral neuropathy if coadministration of thalidomide and cisplatin is necessary. Both drugs can cause peripheral neuropathy, which may be additive.
Tobramycin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
Torsemide: (Moderate) Closely monitor renal function and audiometric testing if concomitant use of cisplatin and torsemide is necessary. Both cisplatin and torsemide can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Trandolapril; Verapamil: (Minor) The absorption of verapamil can be reduced by the vindesine, doxorubicin, cisplatin (VAC) chemotherapeutic drug regimen.
Trilaciclib: (Moderate) Closely monitor renal function if concomitant use of trilaciclib and cisplatin is necessary. Trilaciclib is an OCT2 and MATE inhibitor that may increase cisplatin exposure and alter the net accumulation of cisplatin in the kidney which may be associated with dose-related nephrotoxicity.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valacyclovir: (Moderate) Closely monitor renal function if concomitant use with cisplatin and valacyclovir is necessary. Cisplatin can cause nephrotoxicity. Valacyclovir can cause renal impairment or renal failure, which may be additive when used with cisplatin.
Valganciclovir: (Moderate) Concomitant use of cisplatin and valganciclovir should be considered only if the potential benefits outweigh the risks of increased treatment-related toxicities. If coadministration is necessary, closely monitor for treatment-related adverse reactions. Valganciclovir is rapidly and extensively converted to ganciclovir. Ganciclovir is eliminated renally and cisplatin can cause nephrotoxicity, which may result in increased plasma concentrations of ganciclovir. Side effects such as nephrotoxicity and myelosuppression may be additive.
Vancomycin: (Moderate) Closely monitor renal function and audiometric testing if concomitant use with cisplatin and vancomycin is necessary. Both cisplatin and vancomycin can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Verapamil: (Minor) The absorption of verapamil can be reduced by the vindesine, doxorubicin, cisplatin (VAC) chemotherapeutic drug regimen.
Voclosporin: (Moderate) Concomitant use of voclosporin and cisplatin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.

How Supplied

Cisplatin/Platinol -AQ Intravenous Inj Sol: 1mg, 1mL
Cisplatin/Platinol Intravenous Inj Pwd F/Sol: 50mg

Maximum Dosage
Adults

100 mg/m2 IV.

Geriatric

100 mg/m2 IV.

Adolescents

40 mg/m2 IV.

Children

40 mg/m2 IV.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Cisplatin is an alkylating agent. In the blood, cisplatin is present in an inactive, uncharged state due to the high concentration of chloride ions. Intracellularly, cisplatin loses its two chloride groups and becomes a positively charged electrophilic compound. Cisplatin becomes activated once it enters the cell. It binds to the N7 reactive center on guanine and adenine in the cell nucleus to form interstrand and intrastrand crosslinks. This interferes with normal transcription and/or DNA replication mechanisms, causing DNA damage, blocking cell division, and resulting in apoptosis. While considered cell-cycle non-specific, cells are most sensitive to cisplatin in the G1-phase, just prior to the onset of DNA synthesis. Cisplatin exposure increases the duration of S-phase and causes a dose-dependent inhibition of cells in the G2-phase, resulting in cell cycle arrest and programmed cell death or apoptosis. Other mechanisms of cisplatin cytotoxicity include mitochondrial damage, decreased ATPase activity, and altered cellular transport mechanisms.

Pharmacokinetics

Cisplatin is administered intravenously. Platinum from cisplatin, but not cisplatin itself, is bound to several plasma proteins including albumin, transferrin, and gamma globulin. Three hours after a bolus injection and 2 hours after the end of a 3-hour infusion, 90% of plasma platinum is protein bound. It exhibits reversible binding to plasma protein that is characteristic of normal drug-protein binding. The albumin-platinum complexes do not significantly dissociate and are slowly eliminated with a minimum half-life of at least 5 days. Platinum is present in tissues for up to 180 days after the last administration of cisplatin doses ranging from 20 mg/m2 to 120 mg/m2. Platinum tumor concentrations are somewhat lower than the concentrations in the organ where the tumor is located, except for intracerebral tumors. Hepatic metastases have the highest platinum concentrations, which are similar to the platinum concentrations in normal liver. The chlorine atoms of cisplatin are more subject to chemical displacement reactions by nucleophiles, such as water or sulfhydryl groups, than to enzyme-catalyzed metabolism. Cisplatin and monohydroxymonochloro cis-diamine platinum (II) are present in almost equal concentrations at physiological pH. Monohydroxymonochloro cis-diamine platinum (II), combined with possible direct displacement of chlorine atoms by sulfhydryl groups of amino acids or proteins, accounts for the instability of cisplatin in biological matrices. The plasma ratio of cisplatin to total free (ultrafilterable) platinum has considerable interpatient variability, ranging from 0.5 to 1.1 after a single dose of 100 mg/m2. After a 7 hour infusion, the cisplatin volume of distribution at steady-state was about 11 to 12 liters/m2.
 
After a 7 hour infusion, the total body clearance of cisplatin at steady-state was approximately 15 to 16 liters/hour/m2. The mean renal clearance of cisplatin was 50 to 62 mL/min/m2, exceeding creatinine clearance. The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate, indicating that cisplatin or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion and possible tubular reabsorption. No significant relationships exist between the renal clearance of either free platinum or cisplatin and creatinine clearance. Cisplatin concentrations decrease monoexponentially with a half-life of approximately 20 to 30 minutes. Red blood cell platinum concentrations decline in a biphasic manner with a terminal half-life of 36 to 47 days. Cisplatin is excreted in the urine, with 13% to 17% of a 50 mg/m2 dose in the urine within 1 hour of administration. When a single dose of cisplatin (40 mg/m2 to 140 mg/m2) is given as an IV bolus or IV infusion (range, 1 hour to 24 hours), between 10% to 50% of the administered platinum is excreted in the urine within 24 hours, mostly within the first few hours; only a small percentage of the administered platinum is excreted beyond 24 hours. After 5 daily administrations of cisplatin (20 mg/m2 to 50 mg/m2), the mean urinary platinum recovery ranged from 14% to 30% of the dose. The mean urinary platinum recovery was 35% to 51% after 5 daily administrations of cisplatin 40 mg/m2 to 100 mg/m2.
 
Affected cytochrome P450 isoenzymes or transporters: None

Intravenous Route

Maximum red blood cell platinum concentrations are reached within 90 to 150 minutes after a 100 mg/m2 dose of cisplatin.

Pregnancy And Lactation
Pregnancy

Pregnancy should be avoided by females of reproductive potential during cisplatin treatment and for at least 14 months after the last dose. Based on human data from published literature, cisplatin can cause fetal harm when administered during pregnancy. Women who are pregnant or who become pregnant while receiving cisplatin should be apprised of the potential hazard to the fetus. Data demonstrates placental transfer of cisplatin. Exposure of pregnant women to cisplatin-containing chemotherapy has been associated with oligohydramnios, intrauterine growth restriction, and preterm birth. Cases of neonatal acute respiratory distress syndrome, cytopenias, and hearing loss have been reported. In animal studies, teratogenicity occurred with cisplatin administration both during and after organogenesis. Placental transfer of cisplatin in mice increased with placenta maturation.[28393]

Due to the potential for serious adverse reactions in nursing infants from cisplatin and because of the potential for tumorigenicity shown for cisplatin, advise women to discontinue breast-feeding during treatment. Limited data from published literature report the presence of cisplatin in human milk in low amounts.[28393]