Version November 2024
Cisplatin can cause severe myelosuppression with fatalities due to infections. Monitor blood counts accordingly. Interruption of therapy may be required.
Cisplatin can cause severe nausea and vomiting. Use highly effective antiemetic premedication.
Cisplatin can cause severe renal toxicity, including acute renal failure. Severe renal toxicities are dose-related and cumulative. Ensure adequate hydration and monitor renal function and electrolytes. Consider dose reductions or alternative treatments in patients with renal impairment.
Cisplatin can cause dose-related peripheral neuropathy that becomes more severe with repeated courses of the drug.
Note: Dosing units variable (mg/kg, mg/m2); use caution. Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
TO PREVENT POSSIBLE OVERDOSE, VERIFY ANY CISPLATIN DOSE EXCEEDING 100 mg/m2 PER COURSE (eg, every 3 to 4 week cycle). Pretreatment hydration is recommended.
Germ cell tumors: Limited data available:
Cushing 2004:
Infants: IV: 0.7 mg/kg on days 1 to 5 of a 21-day cycle (in combination with bleomycin and etoposide).
Children and Adolescents: IV: 20 mg/m2 on days 1 to 5 of a 21-day cycle (in combination with bleomycin and etoposide).
Pinkerton 1986: Children and Adolescents: IV: 100 mg/m 2on day 1 of a 21-day cycle (in combination with bleomycin and vinblastine or etoposide).
Lopes 2016: Children and Adolescents:
Intermediate risk: PE regimen: IV: 35 mg/m2 on days 1, 2, and 3 of a 21-day cycle for 3 cycles (weeks 1, 4, and 7) in combination with etoposide; a fourth cycle may be considered depending on response.
High risk: PEI regimen: IV: 35 mg/m2 on days 1, 2, and 3 of a 21-day cycle for 4 cycles (weeks 1, 4, 7, and 11) in combination with etoposide and ifosfamide; a fifth or sixth cycle may be considered depending on response.
Hepatoblastoma: Limited data available:
Continuous IV infusion:
Infants and Children <10 kg: PLADO regimen: IV infusion: 2.7 mg/kg/day continuous infusion over 24 hours on day 1 of a 21-day cycle in combination with doxorubicin for 4 to 6 cycles (Ref).
Children ≥10 kg and Adolescents:
Monotherapy: Standard risk: IV infusion: 80 mg/m2/day continuous infusion over 24 hours every 2 weeks on day 1.
Combination therapy: PLADO regimen: IV infusion: 80 mg/m2/day continuous infusion over 24 hours on day 1 of a 21-day cycle in combination with doxorubicin (Ref) or doxorubicin and sorafenib (Ref).
Intermittent infusion (over 6 hours), C5V(D) regimen:
Infants and Children <10 kg: IV: 3 to 3.3 mg/kg over 6 hours on day 1 of a 21-day cycle for 4 to 8 cycles in combination with vincristine and fluorouracil and/or doxorubicin (Ref).
Children ≥10 kg and Adolescents: IV: 90 to 100 mg/m2 over 6 hours on day 1 of a 21-day cycle for 4 to 8 cycles in combination with vincristine and fluorouracil and/or doxorubicin (Ref).
Medulloblastoma: Limited data available: Children ≥3 years and Adolescents: IV: 75 mg/m2 every 6 weeks on either day 0 of chemotherapy cycle in combination with vincristine and cyclophosphamide or day 1 of chemotherapy cycle in combination with lomustine and vincristine for 8 cycles (Ref).
Medulloblastoma/Primitive neuroectodermal tumor, relapsed or refractory: Very limited data available: Children and Adolescents: IV: 60 mg/m2 on day 0 every 4 weeks (in combination with irinotecan, vincristine, cyclophosphamide, and etoposide) (Ref).
Osteosarcoma: Limited data available: Children and Adolescents: IV: 60 mg/m2/day for 2 days at weeks 2, 7, 25, and 28 (neoadjuvant) or weeks 5, 10, 25, and 28 (adjuvant) in combination with doxorubicin (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: In adult patients, the manufacturer(s) recommend that repeat courses of cisplatin should not be given until serum creatinine is <1.5 mg/dL and/or BUN is <25 mg/dL and use is contraindicated in preexisting renal impairment. Consult protocols for specific renal impairment dosing adjustments. The following adjustments have been recommended:
Aronoff 2007: Infants, Children, and Adolescents:
GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose.
GFR <10 mL/minute/1.73 m2: Administer 50% of dose.
Hemodialysis: Partially cleared by hemodialysis: Administer 50% of dose posthemodialysis.
Peritoneal dialysis: Administer 50% of dose.
Continuous renal replacement therapy (CRRT): Administer 75% of dose.
Katzenstein 2019: Hepatoblastoma: Infants, Children, and Adolescents:
GFR >60 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR <60 mL/minute/1.73 m2: Omit cisplatin dose from regimen until GFR is >60 mL/minute/1.73 m2.
There are no dosage adjustments provided in the manufacturer's labeling; however, cisplatin undergoes nonenzymatic metabolism and predominantly renal elimination; therefore, dosage adjustment is likely not necessary.
(For additional information see "Cisplatin: Drug information")
Dosage guidance:
Safety: Administer appropriate pretreatment hydration and maintain adequate hydration and urinary output for 24 hours following cisplatin administration. Consider magnesium supplementation as clinically indicated. Cisplatin doses exceeding 100 mg/m2 per treatment course are rarely used and should be verified with the prescriber.
Clinical considerations: Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref). Refer to the protocol or institutional guidance for additional details of off-label dosing.
Adrenocortical carcinoma, advanced (off-label use): IV: 40 mg/m2 on days 3 and 4 every 4 weeks (in combination with doxorubicin, etoposide, and mitotane) (Ref) or 40 mg/m2 on days 2 and 9 every 4 weeks (in combination with doxorubicin, etoposide, and mitotane) until disease progression or unacceptable toxicity up to a maximum of 6 cycles (Ref).
Anal carcinoma, squamous cell, metastatic or unresectable locally recurrent (off-label use): IV: 75 mg/m2 on day 1 every 4 weeks (in combination with continuous infusion fluorouracil); patients received a median of 4 cycles in the study (Ref) or 40 mg/m2 on day 1 every 2 weeks (in combination with docetaxel and fluorouracil; modified DCF regimen) for 8 cycles (Ref).
Biliary tract cancer, advanced (off-label use): IV: 25 mg/m2 over 2 hours on days 1 and 8 every 3 weeks (in combination with gemcitabine) for 4 to 8 cycles (Ref) or 25 mg/m2 on days 1 and 8 every 3 weeks (in combination with durvalumab and gemcitabine) for up to 8 cycles, followed by durvalumab as a single agent until disease progression or unacceptable toxicity (Ref) or 25 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 8 cycles (in combination with pembrolizumab [maximum 35 cycles] and gemcitabine until disease progression or unacceptable toxicity) (Ref).
Bladder cancer, advanced: IV: 50 to 70 mg/m2 every 3 to 4 weeks; heavily pretreated patients: 50 mg/m2 every 4 weeks.
Bladder cancer, advanced (off-label dosing/combinations):
Locally advanced or metastatic disease:
Dose-dense MVAC regimen: IV: 70 mg/m2 on day 2 every 14 days (in combination with methotrexate, vinblastine, doxorubicin, and growth factor support) until disease progression or unacceptable toxicity (Ref).
GC regimen: IV: 70 mg/m2 on day 2 every 28 days (in combination with gemcitabine) for up to 6 cycles (Ref). Split-dose cisplatin may be an option in select patients (Ref).
MVAC regimen: IV: 70 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and doxorubicin) for up to 6 cycles (von der Maase 2000) or 70 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and doxorubicin) until disease progression or unacceptable toxicity (Ref) or 70 mg/m2 on day 1 every 28 days (in combination with methotrexate, vinblastine, doxorubicin, and filgrastim) for up to 6 cycles or until loss of clinical benefit (Ref).
Paclitaxel/cisplatin/gemcitabine (PCG) regimen: IV: 70 mg/m2 on day 1 every 3 weeks (in combination with paclitaxel and gemcitabine) for up to 6 cycles or until disease progression or unacceptable toxicity (Ref).
Urothelial carcinoma (bladder, renal pelvis, ureter, or urethra), unresectable or metastatic: IV: 70 mg/m2 over 30 to 120 minutes on day 1 every 21 days (in combination with nivolumab and gemcitabine) for up to 6 cycles, followed by nivolumab (as a single agent) until disease progression, unacceptable toxicity, or for up to 2 years (Ref).
Neoadjuvant treatment:
Note: Patients with non-organ confined disease at cystectomy who did not receive cisplatin-based neoadjuvant chemotherapy should be offered an adjuvant cisplatin-based chemotherapy regimen. Some patients with borderline renal function may be treated with split-dose cisplatin and aggressive hydration (Ref).
Dose-dense MVAC regimen: IV: 70 mg/m2 on day 1 or on day 2 every 14 days (in combination with methotrexate, doxorubicin, and vinblastine) for 3 or 4 cycles (Ref) or 70 mg/m2 on day 1 or on day 2 every 14 days (in combination with methotrexate, doxorubicin, and vinblastine) for 6 cycles (Ref).
GC regimen: IV: 70 mg/m2 on day 1 every 21 days (in combination with gemcitabine) for 4 cycles (Ref) or (split-dose cisplatin) 35 mg/m2 on days 1 and 8 every 21 days (in combination with gemcitabine) for 4 cycles (Ref).
MVAC regimen: IV: 70 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and doxorubicin) for 3 cycles (Ref).
CMV regimen: IV: 100 mg/m2 on day 1 every 21 days (in combination with methotrexate, vinblastine, and leucovorin) for 3 cycles (Ref).
Brain metastases, due to breast or non–small cell lung cancers (off-label use): IV: 100 mg/m2 on day 1 every 3 weeks (in combination with etoposide) for up to 6 cycles in the absence of disease progression or unacceptable toxicity (Ref).
Breast cancer, triple-negative (off-label use): IV: Neoadjuvant therapy (single agent): 75 mg/m2 on day 1 every 3 weeks for 4 cycles (Ref).
Cervical cancer (off-label use): IV: 40 mg/m2 over 4 hours prior to radiation therapy on days 1, 8, 15, 22, 29, and 36 (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil and radiation) for 3 cycles (Ref) or 70 mg/m2 on day 1 every 3 weeks for 4 cycles (in combination with fluorouracil; cycles 1 and 2 given concurrently with radiation) (Ref) or 50 mg/m2 on day 1 every 4 weeks (in combination with radiation and fluorouracil) for 2 cycles (Ref) or 50 mg/m2 on day 1 or day 2 every 3 weeks (in combination with paclitaxel [conventional] and bevacizumab) until disease progression or unacceptable toxicity (Ref) or 50 mg/m2 once every 3 weeks (in combination with paclitaxel [conventional]) for up to 6 cycles in nonresponders, patients with a clinical response could continue beyond 6 cycles (Ref) or 50 mg/m2 on day 1 every 3 weeks (in combination with topotecan) for a maximum of 6 cycles (in nonresponders) or until disease progression or unacceptable toxicity (Ref) or 50 mg/m2 on day 1 or day 2 every 3 weeks (in combination with pembrolizumab and paclitaxel [conventional] ± bevacizumab) for 6 cycles; patients could continue chemotherapy beyond 6 cycles if experiencing clinical benefit without unacceptable toxicity (Ref) or 50 mg/m2 on day 1 every 3 weeks (in combination with paclitaxel [conventional], atezolizumab, and bevacizumab) for at least 6 cycles or until disease progression or unacceptable toxicity; patients with a complete response after 6 cycles could discontinue chemotherapy and continue atezolizumab and bevacizumab (Ref).
Endometrial carcinoma, recurrent, metastatic, or high-risk (off-label use): IV: 50 mg/m2 on day 1 every 3 weeks (in combination with doxorubicin ± paclitaxel) for 7 cycles or until disease progression or unacceptable toxicity (Ref).
Esophageal, gastric, and gastroesophageal cancers (off-label uses):
Pembrolizumab/trastuzumab/cisplatin/fluorouracil (HER2-positive gastric or gastroesophageal junction adenocarcinoma): IV: 80 mg/m2 on day 1 every 3 weeks for up to 6 cycles (may administer beyond 6 cycles at provider discretion); continue pembrolizumab, trastuzumab, and fluorouracil until disease progression or unacceptable toxicity or (in patients without disease progression) for up to 24 months (Ref).
Pembrolizumab/cisplatin/fluorouracil (HER2-negative gastric or gastroesophageal junction adenocarcinoma): IV: 80 mg/m2 on day 1 every 3 weeks (may limit cisplatin to 6 cycles per local guidelines or provider discretion); continue pembrolizumab and fluorouracil until disease progression or unacceptable toxicity or (in patients without disease progression) for up to 24 months (Ref).
Pembrolizumab/cisplatin/fluorouracil (esophageal or gastroesophageal junction cancer): IV: 80 mg/m2 on day 1 every 3 weeks for a maximum of 6 cycles; continue pembrolizumab and fluorouracil until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (Ref).
Nivolumab/cisplatin/fluorouracil (esophageal squamous cell carcinoma): IV: 80 mg/m2 on day 1 every 4 weeks until disease progression or unacceptable toxicity; patients could continue nivolumab for up to 2 years (Ref).
CF regimen (esophageal or gastroesophageal junction cancer): IV: 100 mg/m2 over 30 minutes on days 1 and 29 (preoperative chemoradiation; in combination with fluorouracil) (Ref) or 80 mg/m2 on day 1 (in combination with fluorouracil) every 3 weeks for 2 cycles (neoadjuvant chemotherapy prior to surgery) (Ref).
TCF or DCF regimen (gastric or gastroesophageal junction cancer): IV: 75 mg/m2 on day 1 every 3 weeks (in combination with docetaxel and fluorouracil) until disease progression or unacceptable toxicity (Ref).
Gestational trophoblastic neoplasia, high-risk (off-label use):
EMA-EP regimen: IV: 60 to 80 mg/m2 on day 8 every 2 weeks (in combination with etoposide, methotrexate, leucovorin, and dactinomycin); continue for 2 to 4 treatment cycles after a normal hCG level (Ref).
EP-EMA regimen: EP: IV: 25 mg/m2/dose over 4 hours each for 3 consecutive doses on day 1 (in combination with etoposide), alternating weekly with EMA (etoposide, methotrexate, leucovorin, and dactinomycin) (Ref).
BEP regimen (for refractory disease): IV: 20 mg/m2 on days 1 to 4 of a 21-day cycle (BEP; in combination with bleomycin, etoposide, and WBC growth factor support); continue for at least 2 treatment cycles after a normal hCG level (Ref).
TP/TE regimen (for refractory disease): IV: 60 mg/m2 over 3 hours on day 1 of a 28-day cycle (TP; in combination with paclitaxel) alternating every 2 weeks with TE (paclitaxel and etoposide); continue until hCG level is normal for at least 8 weeks, or until treatment resistance (plateaued or rising hCG) or unacceptable toxicity (Ref).
Low-dose EP induction regimen (consider prior to EMA/CO in patients with high tumor burden): IV: 20 mg/m2 on days 1 and 2 every week (in combination with etoposide) for 1 to 2 cycles, followed by the EMA-CO regimen (etoposide, methotrexate, leucovorin, dactinomycin, cyclophosphamide, and vincristine) until hCG levels normalize and then for a further 6 to 8 weeks (Ref).
Head and neck cancer (off-label use):
Locally advanced disease:
In combination with concurrent radiation therapy: IV: 100 mg/m2 on day 1 every 3 weeks for 3 doses (Ref) or (in patients unable to tolerate the higher standard cisplatin dose) 30 mg/m2 once a week for 6 or 7 weeks, until the end of radiation therapy (Ref) or 40 mg/m2 (maximum dose: 70 mg) once a week during the 7 weeks of radiation therapy (Ref).
In combination with chemotherapy: IV: 75 mg/m2 on day 1 every 3 weeks (in combination with docetaxel and fluorouracil) for 4 cycles or until disease progression or unacceptable toxicity (if no disease progression after 4 cycles, chemotherapy was followed by radiation) (Ref) or 100 mg/m2 on day 1 every 3 weeks (in combination with docetaxel and fluorouracil) for 3 cycles or until disease progression or unacceptable toxicity (chemotherapy was followed by chemoradiation) (Ref).
Metastatic disease: IV: 100 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil and cetuximab) until disease progression or unacceptable toxicity or a maximum of 6 cycles (Ref) or 100 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil and pembrolizumab) for 6 cycles, followed by up to 24 months of pembrolizumab monotherapy (Ref).
Nasopharyngeal carcinoma, locally advanced:
Induction chemotherapy: IV: 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) for 3 cycles followed by concurrent chemoradiotherapy (Ref) or 60 mg/m2 on day 1 every 3 weeks (in combination with docetaxel and fluorouracil; TPF regimen) for 3 cycles, followed by concurrent chemoradiotherapy (Ref) or 60 mg/m2 on day 1 every 3 weeks (in combination with paclitaxel and capecitabine; TPC regimen) for 2 cycles, followed by concurrent chemoradiotherapy (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with docetaxel) for 2 cycles, followed by concurrent chemoradiotherapy (Ref) or 80 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil) for 2 cycles, followed by concurrent chemoradiotherapy (Ref) or 80 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) for 3 cycles, followed by concurrent chemoradiotherapy (Ref). A minimum of 2 induction cycles are recommended (Ref).
Concurrent chemoradiation: IV: 100 mg/m2 on day 1 every 3 weeks for 2 to 3 cycles, concurrently with radiotherapy (Ref) or 40 mg/m2 weekly for 6 to 7 weeks, concurrently with radiotherapy (Ref). If possible, a cu mulative cisplatin dose of at least 200 mg/m2 is recommended (Ref).
Following induction chemotherapy: IV: 100 mg/m2 on day 1 every 3 weeks for 3 cycles concurrently with radiotherapy, following cisplatin and gemcitabine induction chemotherapy (Ref) or 100 mg/m2 on day 1 every 3 weeks for 3 cycles concurrently with radiotherapy, following TPF induction chemotherapy (Ref) or 100 mg/m2 on day 1 every 3 weeks for 2 cycles concurrently with radiotherapy, following TPC induction chemotherapy (Ref) or 40 mg/m2 weekly for 8 weeks concurrently with radiotherapy, following cisplatin and docetaxel induction chemotherapy (Ref) or 80 mg/m2 on day 1 every 3 weeks for 3 cycles concurrently with radiotherapy, following cisplatin and fluorouracil induction chemotherapy (Ref) or 100 mg/m2 on day 1 every 3 weeks for 2 to 3 cycles concurrently with radiotherapy, following cisplatin and capecitabine induction chemotherapy (Ref). If possible, a cumulative cisplatin dose of at least 200 mg/m2 is recommended (Ref).
Prior to adjuvant chemotherapy: IV: 100 mg/m2 on day 1 every 3 weeks for 3 cycles concurrently with radiotherapy, prior to gemcitabine and cisplatin adjuvant chemotherapy (Ref) or 40 mg/m2 weekly for 7 weeks concurrently with radiotherapy, prior to cisplatin and fluorouracil adjuvant chemotherapy (Ref) or 25 mg/m2 over 6 to 8 hours on days 1 to 4 every 3 weeks for 3 cycles concurrently with radiotherapy, followed by cisplatin and fluorouracil adjuvant chemotherapy (Ref) or 100 mg/m2 on day 1 every 3 weeks for 3 cycles concurrently with radiotherapy, followed by cisplatin and fluorouracil adjuvant chemotherapy (Ref). If possible, a cumulative cisplatin dose of at least 200 mg/m2 is recommended (Ref).
Adjuvant therapy: IV: 80 mg/m2 over 4 hours on day 1 every 3 weeks (in combination with gemcitabine) for 3 cycles (Ref) or 80 mg/m2 on day 1 every 4 weeks (in combination with fluorouracil) for 3 cycles (Ref) or 20 mg/m2 over 6 to 8 hours on days 1 to 4 every 4 weeks (in combination with fluorouracil) for 3 cycles (Ref) or 80 mg/m2 on day 1 every 4 weeks (in combination with fluorouracil) for 3 cycles (Ref).
Nasopharyngeal carcinoma, metastatic or recurrent, locally advanced (first-line treatment): IV: 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine and toripalimab); continue until disease progression or unacceptable toxicity for up to a maximum of 6 combination cycles (whichever occurred first); followed by toripalimab (as a single agent) until disease progression or unacceptable toxicity (Ref).
Hodgkin lymphoma, relapsed or refractory (off-label use):
DHAP regimen: IV: 100 mg/m2 continuous infusion over 24 hours on day 1 for 2 cycles; median duration between cycle 1 and 2 was 16 days (in combination with dexamethasone and cytarabine) (Ref).
ESHAP regimen: IV: 25 mg/m2 on days 1 to 4 (in combination with etoposide, methylprednisolone, and cytarabine) every 3 to 4 weeks for 3 or 6 cycles (Ref).
Malignant pleural mesothelioma (off-label use): IV: 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed) (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed) until disease progression or unacceptable toxicity (Ref) or 100 mg/m2 on day 1 every 4 weeks (in combination with gemcitabine) (Ref) or 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed and bevacizumab) for up to 6 cycles, followed by bevacizumab maintenance therapy until disease progression or unacceptable toxicity (Ref). The American Society of Clinical Oncology guidelines for malignant pleural mesothelioma recommend first-line platinum/pemetrexed-based therapy for 4 to 6 cycles (Ref).
Multiple myeloma (off-label use):
DT-PACE regimen: IV: 10 mg/m2/day administered as a continuous infusion on days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with dexamethasone, thalidomide, doxorubicin, cyclophosphamide, and etoposide) (Ref).
VDT-PACE regimen: IV: 10 mg/m2/day administered as a continuous infusion on days 1 to 4 of each cycle; repeat every 4 to 6 weeks (in combination with bortezomib, dexamethasone, thalidomide, doxorubicin, cyclophosphamide, and etoposide) (Ref).
DCEP regimen: IV: 10 mg/m2/day administered as a continuous infusion on days 1 to 4 every 21 days (in combination with cyclophosphamide, etoposide, and dexamethasone) until disease progression or unacceptable toxicity (Ref).
Neuroendocrine tumors, metastatic carcinoma (off-label use): IV: 45 mg/m2/day as a continuous infusion on days 2 and 3 every 4 weeks (in combination with etoposide) until disease progression or unacceptable toxicity (Ref) or 80 mg/m2 over 30 minutes on day 1 every 3 weeks (in combination with etoposide) for up to 6 cycles (Ref).
Non-Hodgkin lymphoma, relapsed/refractory (off-label use):
DHAP regimen (for DLBCL): IV: 100 mg/m2 continuous infusion over 24 hours on day 1 every 3 to 4 weeks for 6 to 10 cycles (in combination with dexamethasone and cytarabine) (Ref).
ESHAP regimen: IV: 25 mg/m2/day continuous infusion over 24 hours on days 1 to 4 every 3 to 4 weeks for 6 to 8 cycles (in combination with etoposide, methylprednisolone, and cytarabine) (Ref).
R-GDP or GDP regimen: IV: 75 mg/m2 on day 1 (in combination with gemcitabine and dexamethasone ± rituximab) every 3 weeks for 2 to 6 cycles (Ref).
Non–small cell lung cancer (off-label use): Note: There are multiple cisplatin-containing regimens for the treatment of NSCLC. Several commonly used regimens are listed below:
Neoadjuvant therapy: IV: 75 mg/m2 on day 1 every 3 weeks (in combination with nivolumab and either pemetrexed or gemcitabine) for up to 3 cycles (Ref).
Adjuvant therapy: IV: 100 mg/m2 on day 1 every 4 weeks (in combination with etoposide) for 3 to 4 cycles (Ref) or 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) for 4 cycles (Ref).
Advanced or metastatic disease: IV: 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) for 6 to 10 cycles (Ref) or 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) until disease progression or unacceptable toxicity (Ref) or 100 mg/m2 on day 1 every 4 weeks (in combination with gemcitabine) (Ref) or 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed) for up to 6 cycles or until disease progression or unacceptable toxicity (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with either pemetrexed [non-squamous histology] or gemcitabine [squamous histology], and durvalumab and tremelimumab) for 4 cycles, followed by tremelimumab (for 1 additional dose) and durvalumab; continue durvalumab until disease progression or unacceptable toxicity; optional pemetrexed maintenance therapy could be administered in patients who received pemetrexed initially (if eligible) (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with cemiplimab and either pemetrexed [non-squamous histology only] or paclitaxel) for 4 cycles, followed by cemiplimab (and pemetrexed maintenance therapy in patients who received pemetrexed initially) until disease progression or unacceptable toxicity, or for up to 108 weeks (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed, nivolumab, and ipilimumab; non-squamous histology) for 2 cycles; nivolumab/ipilimumab therapy continued until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression (Ref) or 75 mg/m2 on day 1 every 3 weeks (in combination with osimertinib and pemetrexed) for 4 cycles, followed by osimertinib and pemetrexed until disease progression or unacceptable toxicity (Ref).
Osteosarcoma (off-label use): Adults ≤40 years of age: IV: 60 mg/m2/day (over 4 hours) for 2 days (total of 120 mg/m2/cycle) of weeks 1 and 6 (neoadjuvant therapy) and then 60 mg/m2/day (over 4 hours) for 2 days (total of 120 mg/m2/cycle) of weeks 12 and 17 (adjuvant therapy) in combination with methotrexate, leucovorin, and doxorubicin (Ref).
Ovarian cancer, advanced: IV: 75 to 100 mg/m2 once every 3 to 4 weeks or (off-label combination) 75 mg/m2 every 3 weeks (in combination with paclitaxel) (Ref).
Intraperitoneal (off-label route): 100 mg/m2 on day 2 of a 21-day treatment cycle (in combination with IV and intraperitoneal paclitaxel) for 6 cycles (Ref).
Ovarian germ cell tumors (off-label dosing):
BEP regimen (adjuvant treatment): IV: 20 mg/m2 on days 1 to 5 every 21 days (in combination with bleomycin and etoposide) for 3 cycles (Ref).
EP regimen: IV: 20 mg/m2 on days 1 to 5 every 21 days (in combination with etoposide) for 4 cycles (Ref); while the BEP regimen is preferred in the treatment of ovarian germ cell tumors, EP may be considered if pulmonary toxicity is a concern. Note: Use of this regimen in ovarian germ cell tumors is extrapolated from data in the management of testicular germ cell tumors.
TIP regimen: IV: 25 mg/m2 on days 2 to 5 every 3 weeks (in combination with paclitaxel, ifosfamide, and mesna) for 4 cycles (Ref). Note: Use of this regimen in ovarian germ cell tumors is extrapolated from data in the management of testicular germ cell tumors.
Pancreatic cancer, locally advanced or metastatic (off-label use; alternative regimen): IV: 50 mg/m2 over 1 hour on days 1 and 15 every 4 weeks (in combination with gemcitabine) (Ref).
Penile cancer, metastatic (off-label use): IV: 25 mg/m2 over 2 hours on days 1, 2, and 3 every 3 to 4 weeks (in combination with paclitaxel and ifosfamide) for 4 cycles (Ref).
Primary CNS lymphoma, relapsed or refractory (off-label use; based on limited data): IV: 100 mg/m2 continuous infusion over 24 hours on day 1 every 3 to 4 weeks (in combination with dexamethasone and high-dose cytarabine) for ~6 to 10 cycles in responding patients (Ref).
Prostate cancer, metastatic, castration resistant, small cell variant or with anaplastic feature (off-label use): IV: 25 mg/m2 on days 1, 2, and 3 every 3 weeks (in combination with etoposide, as second-line treatment following first-line treatment with carboplatin and docetaxel) for at least 4 cycles (Ref).
Small cell lung cancer (off-label use):
Limited-stage disease: IV: 60 mg/m2 on day 1 every 3 weeks for 4 cycles (in combination with etoposide and concurrent radiation) (Ref) or 80 mg/m2 on day 1 every 3 weeks (in combination with etoposide and sequential radiation therapy) for 4 cycles (Ref) or 80 mg/m2 on day 1 every 4 weeks (in combination with etoposide and concurrent radiation therapy) for 4 cycles (Ref) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with etoposide) for 6 cycles (Ref).
Extensive-stage disease: IV: 80 mg/m2 on day 1 every 3 weeks (in combination with etoposide) for 4 cycles (Ref) or a maximum of 8 cycles (Ref) or 60 mg/m2 on day 1 every 4 weeks for 4 cycles (in combination with irinotecan) (Ref) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with etoposide) for 6 cycles (Ref).
Testicular cancer, advanced: IV: 20 mg/m2 once daily for 5 days repeated every 3 weeks (in combination with bleomycin and etoposide) (Ref).
Testicular germ cell tumor, metastatic, good-risk (off-label combination): IV: 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with etoposide) for 4 cycles (Ref).
Testicular germ cell tumor, metastatic, intermediate or poor-risk (off-label dosing): IV: 25 mg/m2 on days 2 to 5 every 3 weeks (in combination with paclitaxel, ifosfamide, and mesna) for 4 cycles (Ref) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with bleomycin and etoposide) for 4 cycles (Ref) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with etoposide and ifosfamide) for 4 cycles (Ref) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with vinblastine, ifosfamide, and mesna) for 4 cycles (Ref).
Thymic carcinoma, locally advanced or metastatic (off-label use; based on limited data):
CODE regimen: IV: 25 mg/m2 on day 1 (in combination with vincristine, doxorubicin, and etoposide) during weeks 1, 2, 4, 6, and 8 (Ref).
VIP regimen: IV: 20 mg/m2 on days 1 to 4 (in combination with etoposide, ifosfamide, mesna and colony-stimulating growth factor support) every 3 weeks for up to 4 cycles or until disease progression or unacceptable toxicity (Ref).
Thymomas, advanced or metastatic (off-label use):
CAP regimen: IV: 50 mg/m2 over at least 1 hour on day 1 every 3 weeks for up to 8 cycles (in combination with cyclophosphamide and doxorubicin) (Ref).
ADOC regimen: IV: 50 mg/m2 on day 1 every 3 weeks (in combination with doxorubicin, vincristine, and cyclophosphamide) (Ref).
PE regimen: IV: 60 mg/m2 over 1 hour on day 1 every 3 weeks (in combination with etoposide) for up to 8 cycles (Ref).
VIP regimen: IV: 20 mg/m2 on days 1 to 4 (in combination with etoposide, ifosfamide, mesna, and colony-stimulating growth factor support) every 3 weeks for up to 4 cycles or until disease progression or unacceptable toxicity (Ref).
Unknown primary, squamous cell carcinoma (off-label use; based on limited data): IV: 75 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil ± docetaxel) for 3 cycles (Ref) or 20 mg/m2 on days 1 to 5 every 4 weeks (in combination with fluorouracil) until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Altered kidney function:
Note: Due to nephrotoxicity concerns, alternative agents may be preferred in patients with baseline kidney impairment when clinically appropriate. The manufacturer's labeling suggests consideration of alternative treatments or dose reductions for patients with impaired CrCl, but does not provide specific adjustments. Limited data are available, and the optimal approach to cisplatin dose adjustment is not established. In addition to the recommendations provided below, other general adjustments (Ref) or cancer-specific adjustments (Ref) have also been described.
Therapy with curative intent (Ref):
CrCl ≥60 mL/minute: IV: No dosage adjustment necessary.
CrCl 50 to <60 mL/minute: IV: Administer 75% of the usual indication-specific recommended dose.
CrCl 40 to <50 mL/minute: IV: Administer 50% of the usual indication-specific recommended dose.
CrCl <40 mL/minute: Use is not recommended.
Therapy with palliative intent (Ref):
CrCl ≥60 mL/minute: IV: No dosage adjustment necessary.
CrCl 50 to <60 mL/minute: IV: Administer 75% of the usual indication-specific recommended dose.
CrCl <50 mL/minute: Use is not recommended.
Hemodialysis, intermittent (thrice weekly): Poorly dialyzable due to rapid and high degree of protein binding (Ref).
Note: Although use of cisplatin is generally not recommended in patients with chronic kidney disease (CKD) due to the risk of nephrotoxicity, for patients with irreversible CKD receiving hemodialysis, the concern of nephrotoxicity is no longer relevant and although not routinely recommended, administration of cisplatin in these patients (using various strategies) has been reported (Ref). A commonly recommended approach is described below:
Therapy with curative intent: IV: Administer 50% of the usual indication-specific recommended dose (Ref). Although removal by dialysis is not likely to be substantial, administer cisplatin after hemodialysis (or on a nondialysis day) to allow for cisplatin to distribute into the tissue (Ref).
Therapy with palliative intent: Use is not recommended (Ref).
Peritoneal dialysis: Not significantly dialyzed (Ref):
Therapy with curative intent: IV: Although not routinely recommended, if necessary, administer 50% of the usual indication-specific recommended dose. However, nephrotoxicity is likely in patients with residual kidney function; avoid use in patients with significant residual kidney function (Ref).
Therapy with palliative intent: Use is not recommended (Ref).
CRRT: Use is not recommended, as cisplatin is a nephrotoxin that could prevent the return of or worsen kidney function (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Use is not recommended, as cisplatin is a nephrotoxin that could prevent the return of or worsen kidney function (Ref).
Nephrotoxicity during treatment: Cisplatin-induced nephrotoxicity most commonly presents as acute kidney injury (AKI) and/or as electrolyte disturbances (eg, hypomagnesemia, Fanconi-like syndrome, salt-wasting hyponatremia) (Ref). Patients that develop AKI (eg, SCr >2 times baseline) may require discontinuation of therapy; however, re-treatment may be considered after recovery from AKI if cisplatin is considered life-saving or life-extending. For patients experiencing electrolyte disturbances, if continued use of cisplatin is considered clinically appropriate (ie, patient receiving cisplatin with curative intent and responding to therapy), cisplatin may be continued with appropriate electrolyte repletion. However, if concurrent AKI occurs or electrolyte abnormalities persist even with aggressive supplementation, consider discontinuation of cisplatin therapy and administration of appropriate supportive care (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, cisplatin undergoes nonenzymatic metabolism and predominantly renal elimination. Dosage adjustment is likely not necessary (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Neurotoxicity (peripheral neuropathy is dose and duration dependent)
Gastrointestinal: Nausea and vomiting (76% to 100%)
Genitourinary: Nephrotoxicity (28% to 36%; acute renal failure and chronic renal insufficiency)
Hematologic & oncologic: Anemia (≤40%), leukopenia (25% to 30%; nadir: Day 18 to 23; recovery: By day 39; dose related), thrombocytopenia (25% to 30%; nadir: Day 18 to 23; recovery: By day 39; dose related)
Hepatic: Increased liver enzymes
Otic: Ototoxicity (children 40% to 60%; adults 10% to 31%; as tinnitus, high frequency hearing loss)
1% to 10%: Local: Local irritation
<1%, postmarketing, and/or case reports: Alopecia (mild), ageusia, anaphylaxis, autonomic neuropathy, bradycardia (Schlumbrecht 2015), bronchoconstriction, cardiac arrhythmia, cardiac failure, cerebral arteritis, cerebrovascular accident, dehydration, diarrhea, dysgeusia (Rehwaldt 2009), extravasation, heart block, hemolytic anemia (acute), hemolytic-uremic syndrome, hiccups, hypercholesterolemia, hyperuricemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, hypotension, increased serum amylase, ischemic heart disease, leukoencephalopathy, Lhermitte's sign, mesenteric ischemia (acute; Morgan 2011), myocardial infarction, neutropenic enterocolitis (Furonaka 2005), optic neuritis, pancreatitis (Trivedi 2005), papilledema, peripheral ischemia (acute), phlebitis (Tokuda 2015), reversible posterior leukoencephalopathy syndrome, seizure, SIADH, skin rash, tachycardia, tetany, thrombosis (aortic; Fernandes 2011), thrombotic thrombocytopenic purpura, vasospasm (acute arterial; Morgan 2011), vision color changes, vision loss
Severe hypersensitivity to cisplatin or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other platinum-containing compounds; preexisting renal or hearing impairment (unless benefits outweigh risks); myelosuppression.
Concerns related to adverse effects:
• Bone marrow suppression: Cisplatin may cause severe myelosuppression; fatalities due to infection (secondary to myelosuppression) have been reported. Fever has been reported in patients with neutropenia. Geriatric patients may be at higher risk for hematologic toxicity.
• Extravasation: Cisplatin is a vesicant at higher concentrations, and an irritant at lower concentrations; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Monitor infusion site during administration. Local soft tissue toxicity has been reported following cisplatin extravasation; the severity of the local tissue toxicity appears to be related to the cisplatin concentration. Cisplatin infusion solutions at a concentration >0.5 mg/mL may result in tissue cellulitis, fibrosis, necrosis, pain, edema, and erythema.
• GI toxicity: Cisplatin can cause severe nausea and vomiting; use highly effective antiemetic premedication. Nausea and vomiting are dose-related and may be immediate and/or delayed, usually lasting up to 72 hours, although may persist for up to 1 week. Diarrhea may also occur.
• Hypersensitivity: Cisplatin may cause severe hypersensitivity reactions, including anaphylaxis (some fatal). Manifestations of hypersensitivity include facial edema, wheezing, tachycardia, and hypotension. Hypersensitivity reactions have occurred within minutes of administration (in patients with prior cisplatin exposure). Ensure supportive equipment and medications for management of severe hypersensitivity reactions are available. Cross-reactivity between platinum-based antineoplastic agents has been reported; severe hypersensitivity reactions have recurred following rechallenge with a different platinum agent (case reports).
• Nephrotoxicity: Cisplatin can cause severe renal toxicity, including acute renal failure. Severe renal toxicities are dose related and cumulative. Ensure adequate hydration (before, during, and following cisplatin administration). Acute renal failure may be prolonged and severe with repeat cisplatin courses. The onset of nephrotoxicity usually begins during the second week following a cisplatin dose. Patients with renal impairment at baseline, geriatric patients, those taking other nephrotoxic medications, and/or patients who are not well hydrated may be at higher risk for nephrotoxicity.
• Neurotoxicity: Cisplatin may cause dose-related peripheral neuropathy that becomes more severe with repeated cisplatin courses. Neurotoxicity has been reported following a single cisplatin dose. Neuropathy may be delayed, with an onset occurring 3 to 8 weeks after the last cisplatin dose. Neuropathy manifestations include paresthesias with a stocking-glove distribution, areflexia, and loss of proprioception and vibratory sensation. Neuropathy may progress following cisplatin discontinuation. In some patients, peripheral neuropathy may be irreversible. Geriatric patients may be more susceptible to peripheral neuropathy. Seizures, loss of motor function, loss of taste, leukoencephalopathy, and posterior reversible leukoencephalopathy syndrome have also been described.
• Ocular toxicity: Optic neuritis, papilledema, and cortical blindness have been reported in patients receiving standard recommended cisplatin doses. Blurred vision and altered color perception have been reported after the use of regimens with higher or more frequent cisplatin doses. Altered color perception manifests as a loss of color discrimination, particularly in the blue-yellow axis and irregular retinal pigmentation of the macular area on fundoscopic exam. Improvement and/or total recovery usually occurs following cisplatin discontinuation, although may be delayed.
• Ototoxicity: Cisplatin may cause cumulative and severe ototoxicity. Ototoxicity is manifested by tinnitus, high-frequency (4,000 to 8,000 Hz) hearing loss, and/or decreased ability to hear normal conversational tones. Ototoxicity may occur during or after treatment; may be unilateral or bilateral. Deafness following the initial cisplatin dose has been reported. Vestibular toxicity has also been reported. Ototoxic effects may be more severe and/or detrimental in pediatric patients, particularly those <5 years of age. The prevalence of hearing loss in pediatric patients is estimated to be 40% to 60%. Additional risk factors for ototoxicity include simultaneous cranial irradiation, treatment with other ototoxic medications, and/or renal impairment. Certain genetic variations in the thiopurine S-methyltransferase (TPMT) gene may be associated with an increased risk of ototoxicity in children administered conventional cisplatin doses (Pussegoda 2013). Controversy may exist regarding the role of TPMT variants in cisplatin ototoxicity (Ratain 2013; Yang 2013); the association has not been consistent across populations and studies. Children without the TPMT gene variants may still be at risk for ototoxicity. Cumulative dose, prior or concurrent exposure to other ototoxic agents (eg, aminoglycosides, carboplatin), prior cranial radiation, younger age, and type of cancer may also increase the risk for ototoxicity in children (Knight 2005; Landier 2014). An international grading scale (SIOP Boston scale) has been developed to assess ototoxicity in children (Brock 2012). Sodium thiosulfate (Pedmark) is approved to reduce the risk of ototoxicity from cisplatin infusions that are ≤6 hours in duration when used to treat localized nonmetastatic solid tumors in pediatric patients.
• Secondary malignancies: Secondary malignancies, including acute leukemias, have been reported with cisplatin, usually when used in combination with other chemotherapy agents.
• Tumor lysis syndrome: Hyperuricemia has been reported with cisplatin; consider antihyperuricemic therapy to reduce uric acid levels.
Disease-related concerns:
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition (Mehrizi 2012).
Special populations:
• Older adult: Select dose cautiously and monitor closely in older adult patients; they may be more susceptible to hematologic toxicity, infections, nephrotoxicity, and/or peripheral neuropathy.
Other warnings/precautions:
• Medication safety: Doses >100 mg/m2/cycle (once every 3 to 4 weeks) are rare; verify with the prescriber. At the approved dose, cisplatin should not be administered more frequently than once every 3 to 4 weeks. Exercise caution to avoid inadvertent overdose due to potential sound-alike/look-alike confusion between CISplatin and CARBOplatin or prescribing practices that fail to differentiate daily doses from the total dose per cycle.
Compared to older patients, pediatric patients, especially those <5 years of age, are at increased risk for the development of ototoxicity that has been observed to be more severe and/or detrimental due to speech and language development during this time. The prevalence of hearing loss in pediatric patients is estimated to be 40% to 60%. Cumulative dose, prior or concurrent exposure to other ototoxic agents (eg, aminoglycosides, carboplatin), prior or concurrent cranial irradiation, younger age, and type of cancer may increase the risk for ototoxicity in children (Knight 2005; Landier 2014). To assess ototoxicity, an international grading scale (SIOP Boston scale) has been developed to (Brock 2012). Sodium thiosulfate (Pedmark) is approved to reduce the risk of ototoxicity from cisplatin infusions that are ≤6 hours in duration when used to treat localized nonmetastatic solid tumors in pediatric patients.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Kemoplat: 50 mg/50 mL (50 mL)
Generic: 50 mg/50 mL (50 mL); 100 mg/100 mL (100 mL)
Solution, Intravenous [preservative free]:
Generic: 50 mg/50 mL (50 mL); 100 mg/100 mL (100 mL); 200 mg/200 mL (200 mL)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 50 mg (1 ea)
Yes
Solution (CISplatin Intravenous)
50 mg/50 mL (per mL): $0.37 - $0.87
100 mg/100 mL (per mL): $0.23 - $0.49
200 mg/200 mL (per mL): $0.49 - $0.66
Solution (reconstituted) (CISplatin Intravenous)
50 mg (per each): $600.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 mg/mL (10 mL, 50 mL, 100 mL)
Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Pretreatment hydration is recommended prior to cisplatin administration; adequate posthydration and urinary output (eg, >100 mL/hour in adults) should be maintained for 24 hours after administration.
IV: Infuse over 6 to 8 hours; has also been infused over 30 minutes to 3 hours, at a rate of 1 mg/minute, or as a continuous infusion; infusion rate varies by protocol (refer to specific protocol for infusion details)
Needles or IV administration sets that contain aluminum should not be used for administration; aluminum may react with cisplatin resulting in precipitate formation and loss of potency.
Vesicant (at higher concentrations); ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate sodium thiosulfate antidote; elevate extremity. Dimethyl sulfoxide (DMSO) may also be considered an option (See Management of Drug Extravasations for more details).
Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref). Administer appropriate pretreatment hydration and maintain adequate hydration and urinary output for 24 hours following cisplatin administration.
IV: Cisplatin has been infused over 30 minutes to 4 hours, at a rate of 1 mg/minute, or as a continuous infusion (off-label rates); infusion rate varies by protocol (refer to specific protocol for infusion details). Do not administer as a rapid IV injection. Also refer to specific protocol for information regarding recommended concomitant hydration, diuretics, and (for combination regimens) the administration sequence.
Intraperitoneal (off-label route): Solution was prepared in warmed saline and infused as rapidly as possible through an implantable intraperitoneal catheter (Ref).
Needles or IV administration sets that contain aluminum should not be used in the preparation or administration; aluminum may react with cisplatin resulting in precipitate formation and loss of potency.
Vesicant (at higher concentrations); ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate sodium thiosulfate antidote; elevate extremity.
Sodium thiosulfate 1/6 M solution: Inject 2 mL into existing IV line for each 100 mg of cisplatin extravasated; then consider also injecting 1 mL as 0.1 mL subcutaneous injections (clockwise) around the area of extravasation, may repeat subcutaneous injections several times over the next 3 to 4 hours (Ref).
Dimethyl sulfoxide (DMSO) may also be considered an option: Apply to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (Ref).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Lyophilized powder: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store in original carton prior to reconstitution to protect from light. The reconstituted solution is stable for 20 hours at 20°C to 25°C (68°F to 77°F); do not refrigerate. Solution removed from amber vial should be protected from light if not used within 6 hours.
Solution: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. Do not refrigerate solution (precipitate may form). According to the manufacturer, after initial entry into the vial, solution is stable for 28 days protected from light or for at least 7 days under fluorescent room light at room temperature.
When diluted for administration in D51/4NS, D51/2NS, D5NS, 1/4NS, 1/3NS, 1/2NS, or NS, cisplatin stability is dependent on the chloride ion concentration.
Treatment of metastatic testicular cancer, advanced bladder cancer, and metastatic ovarian cancers (FDA approved in adults); has also been used in the treatment of central nervous system tumors, germ cell tumors, hepatoblastoma, medulloblastoma, neuroblastoma, and osteosarcoma.
CISplatin may be confused with CARBOplatin, oxaliplatin
Platinol may be confused with Patanol
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Cisplatin doses >100 mg/m2 once every 3 to 4 weeks are rarely used and should be verified with the prescriber.
Substrate of OCT2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Alpha-Lipoic Acid: May diminish the therapeutic effect of CISplatin. Risk C: Monitor therapy
Aminoglycosides: CISplatin may enhance the nephrotoxic effect of Aminoglycosides. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Antithyroid Agents: Myelosuppressive Agents may enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Capecitabine: CISplatin may enhance the nephrotoxic effect of Capecitabine. Risk C: Monitor therapy
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fosphenytoin-Phenytoin: Platinum Derivatives may decrease the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Linezolid: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Loop Diuretics: May enhance the nephrotoxic effect of CISplatin. Loop Diuretics may enhance the ototoxic effect of CISplatin. Risk C: Monitor therapy
Melphalan: CISplatin may increase the serum concentration of Melphalan. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Netilmicin (Ophthalmic): CISplatin may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Systemic): CISplatin may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Management: Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane before platinum is likely warranted Risk D: Consider therapy modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of Topotecan. Management: Consider administering platinum derivatives after topotecan when possible to minimize toxicity or using lower doses if administering platinum derivatives prior to topotecan. Monitor for hematologic toxicity (eg, neutropenia, thrombocytopenia). Risk D: Consider therapy modification
Trilaciclib: May increase the serum concentration of CISplatin. Risk C: Monitor therapy
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vinorelbine: CISplatin may enhance the adverse/toxic effect of Vinorelbine. Specifically, the combination may be associated with a higher risk of granulocytopenia. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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Verify pregnancy status prior to treatment initiation in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during treatment and for 14 months after the last cisplatin dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 11 months after the last cisplatin dose.
Cisplatin has been associated with cumulative dose-dependent ovarian failure, premature menopause, impairment of spermatogenesis (oligospermia, azoospermia; possibly irreversible), and reduced female and male fertility. Recommendations are available for fertility preservation of male and female patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).
Cisplatin crosses the human placenta (Köhler 2015).
Outcome data following maternal use of cisplatin during pregnancy are available (Bernardini 2022; NTP 2013; Pei 2022; Song 2018; Wang 2022; Zagouri 2013). Cisplatin may cause fetal harm if administered during pregnancy. Adverse events associated with cisplatin containing regimens include oligohydramnios, intrauterine growth restriction, and preterm birth; acute respiratory distress syndrome, cytopenias, and hearing loss have been reported in the neonate. Children with in utero exposure to cisplatin should be monitored for hearing loss (Amant 2019).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery (for adequate maternal and fetal bone marrow recovery), and chemotherapy should not be administered beyond week 33 of gestation. When indicated, chemotherapy may be administered during the second or third trimester at the same dose and schedule as recommended for nonpregnant patients (Amant 2019; ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
Renal function tests (serum creatinine, BUN, CrCl), electrolytes (particularly magnesium, calcium, potassium), ototoxicity assessment (SIOP Boston scale: Baseline and prior to each subsequent dose and following treatment), neurologic exam (with high dose), liver function tests periodically, CBC with differential and platelet count (weekly), urine output, urinalysis, urine specific gravity.
Cisplatin inhibits DNA synthesis by the formation of DNA cross-links; denatures the double helix; covalently binds to DNA bases and disrupts DNA function; may also bind to proteins; the cis-isomer is 14 times more cytotoxic than the trans-isomer; both forms cross-link DNA but cis-platinum is less easily recognized by cell enzymes and, therefore, not repaired. Cisplatin can also bind two adjacent guanines on the same strand of DNA producing intrastrand cross-linking and breakage.
Distribution: IV: 11 to 12 L/m2
Protein binding: Plasma platinum: >90%
Metabolism: Nonenzymatic; inactivated (in both cell and bloodstream) by sulfhydryl groups; covalently binds to glutathione and thiosulfate
Half-life elimination:
Children: Free drug: 1.3 hours; Total platinum: 44 hours
Adults: Cisplatin: 20 to 30 minutes; Platinum: ≥5 days
Excretion: Cisplatin: Urine (13% to 17% within 1 hour); Platinum: Urine (35% to 51%)
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