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: Administer appropriate pretreatment hydration and maintain adequate hydration and urinary output for 24 hours following cisplatin administration. Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Cisplatin doses exceeding 100 mg/m2 per treatment course are rarely used and should be verified with the prescriber.
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) (Fassnacht 2012) 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 (Berruti 2005).
Anal carcinoma, squamous cell, metastatic (off-label use; based on limited data): IV: 75 mg/m2 on day 1 every 4 weeks (in combination with continuous infusion fluorouracil) (Eng 2014).
Biliary tract cancer, advanced (off-label use): IV: 25 mg/m2 over 2 hours on days 1 and 8; repeat cycle every 3 weeks (in combination with gemcitabine) for 4 to 8 cycles (Valle 2010).
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 (Sternberg 2001; Sternberg 2006).
GC regimen: IV: 70 mg/m2 on day 2 every 28 days (in combination with gemcitabine) for up to 6 cycles (von der Maase 2000). Split-dose cisplatin may be an option in select patients (Kim 2015).
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 (Sternberg 2001; Sternberg 2006) 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 (Bamias 2004).
Paclitaxel/gemcitabine/cisplatin (PGC) regimen: IV: 70 mg/m2 on day 2 every 3 weeks (in combination with gemcitabine and paclitaxel; refer to protocol for administration sequence details) for up to 6 cycles or until disease progression or unacceptable toxicity (Bellmunt 2012).
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 (AUA/ASCO/ASTRO/SUO [Chang 2017]).
Dose-dense MVAC regimen: IV: 70 mg/m2 on day 1 or on day 2 every 14 days (in combination with methotrexate, doxorubicin, vinblastine, and pegfilgrastim) for 3 or 4 cycles (Choueiri 2014; Plimack 2014).
GC regimen: IV: 70 mg/m2 on day 1 every 21 days or (split-dose cisplatin) 35 mg/m2 on days 1 and 8 every 21 days (in combination with gemcitabine) for 4 cycles (Dash 2008).
MVAC regimen: IV: 70 mg/m2 on day 2 every 28 days (in combination with methotrexate, vinblastine, and doxorubicin) for 3 cycles (Grossman 2003).
CMV regimen: IV: 100 mg/m2 on day 1 every 21 days (in combination with methotrexate, vinblastine, and leucovorin) for 3 cycles (Griffiths 2011).
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 (Franciosi 1999).
Breast cancer, triple-negative (off-label use): IV: Neoadjuvant therapy (single agent): 75 mg/m2 on day 1 every 3 weeks for 4 cycles (Silver 2010).
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 (Rose 2007) or 75 mg/m2 on day 1 every 3 weeks (in combination with fluorouracil and radiation) for 3 cycles (Morris 1999) 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) (Peters 2000) or 50 mg/m2 on day 1 every 4 weeks (in combination with radiation and fluorouracil) for 2 cycles (Whitney 1999) 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 (Tewari 2014; Tewari 2017) 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 (Monk 2009; Moore 2004) 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 (Long 2005) 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; refer to protocol for further information (Colombo 2021).
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 (Fleming 2004).
Esophageal, gastroesophageal, and gastric cancers (off-label uses):
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 (Sun 2021). Refer to protocol for further details.
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) (Tepper 2008) or 80 mg/m2 on day 1 (in combination with fluorouracil) every 3 weeks for 2 cycles (neoadjuvant chemotherapy prior to surgery) (Alderson 2017).
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 (Ajani 2007; Van Cutsem 2006).
Gestational trophoblastic neoplasia, high-risk metastatic disease (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 (Ghaemmaghami 2004).
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) (Newlands 2000).
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 (Bernier 2004; Cooper 2004) 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 (Ghosh-Laskar 2016; Noronha 2018).
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) (Vermorken 2007) 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) (Posner 2007).
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 (Vermorken 2008).
Hodgkin lymphoma, relapsed/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) (Josting 2002).
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 (Aparicio 1999).
Malignant pleural mesothelioma (off-label use): IV: 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed) (Vogelzang 2003) or 75 mg/m2 on day 1 every 3 weeks (in combination with pemetrexed) until disease progression or unacceptable toxicity (Santoro 2008) or 100 mg/m2 on day 1 every 4 weeks (in combination with gemcitabine) (Nowak 2002) or 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) (van Haarst 2002) 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 (Zalcman 2016). The American Society of Clinical Oncology guidelines for malignant pleural mesothelioma recommend first-line platinum/pemetrexed-based therapy for 4 to 6 cycles (ASCO [Kindler 2018]).
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) (Lee 2003).
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) (Lee 2003; Pineda-Roman 2008).
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 (Lazzarino 2001; Park 2014).
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 (Fjällskog 2001; Moertel 1991) or 80 mg/m2 over 30 minutes on day 1 every 3 weeks (in combination with etoposide) for up to 6 cycles (Le Treut 2013).
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) (Velasquez 1988).
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) (Velasquez 1994).
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 (Crump 2004; Crump 2014).
Non-small cell lung cancer (NSCLC; off-label use): Note: There are multiple cisplatin-containing regimens for the treatment of NSCLC. Several commonly used regimens are listed below:
Adjuvant therapy: IV: 100 mg/m2 on day 1 every 4 weeks (in combination with etoposide) for 3 to 4 cycles (Arriagada 2004) or 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) for 4 cycles (Douillard 2006).
Advanced or metastatic disease: IV: 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) for 6 to 10 cycles (Kelly 2001) or 100 mg/m2 on day 1 every 4 weeks (in combination with vinorelbine) until disease progression or unacceptable toxicity (Wozniak 1998) or 100 mg/m2 on day 1 every 4 weeks (in combination with gemcitabine) (Comella 2000) or 80 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity (Ohe 2007) 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 (Scagliotti 2008).
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 (Marina 2016; Whelan 2015).
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) (Ozols 2003).
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 (Armstrong 2006).
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 (Williams 1994).
EP regimen: IV: 20 mg/m2 on days 1 to 5 every 21 days (in combination with etoposide) for 4 cycles (Culine 2007); 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 (Kondagunta 2005b). 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) (Heinemann 2006).
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 (Pagliaro 2010).
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 (Velasquez 1988; McLaughlin 1988).
Prostate cancer, castration-resistant, metastatic (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 (Aparicio 2013).
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) (Turrisi 1999) or 80 mg/m2 on day 1 every 3 weeks (in combination with etoposide and sequential radiation therapy) for 4 cycles (Takada 2002) or 80 mg/m2 on day 1 every 4 weeks (in combination with etoposide and concurrent radiation therapy) for 4 cycles (Takada 2002) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with etoposide) for 6 cycles (Evans 1985).
Extensive-stage disease: IV: 80 mg/m2 on day 1 every 3 weeks (in combination with etoposide) for 4 cycles (Lara 2009) or a maximum of 8 cycles (Ihde 1994) or 60 mg/m2 on day 1 every 4 weeks for 4 cycles (in combination with irinotecan) (Lara 2009) or 25 mg/m2 on days 1, 2, and 3 every 3 to 4 weeks (in combination with etoposide) for 6 cycles (Evans 1985).
Testicular cancer, advanced: IV: 20 mg/m2 once daily for 5 days repeated every 3 weeks (in combination with bleomycin and etoposide) (Cushing 2004; Saxman 1998).
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 (Culine 2007; Kondagunta 2005a).
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 (Kondagunta 2005b) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with bleomycin and etoposide) for 4 cycles (Nichols 1998) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with etoposide and ifosfamide) for 4 cycles (Nichols 1998) or 20 mg/m2 on days 1 to 5 every 3 weeks (in combination with vinblastine, ifosfamide, and mesna) for 4 cycles (Loehrer 1998).
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 (Yoh 2003).
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 (Loehrer 2001).
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) (Loehrer 1994).
ADOC regimen: IV: 50 mg/m2 on day 1 every 3 weeks (in combination with doxorubicin, vincristine, and cyclophosphamide) (Fornasiero 1991).
PE regimen: IV: 60 mg/m2 over 1 hour on day 1 every 3 weeks (in combination with etoposide) for up to 8 cycles (Giaccone 1996).
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 (Loehrer 2001).
Unknown primary, adenocarcinoma (off-label use): IV: 100 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine) (Culine 2003; Gross-Goupil 2012) or 80 mg/m2 on day 1 every 3 weeks (in combination with docetaxel) for 2 to 6 cycles (Mukai 2010).
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 (Pointreau 2009) or 20 mg/m2 on days 1 to 5 every 4 weeks (in combination with fluorouracil) until disease progression or unacceptable toxicity (Kusaba 2007).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: The manufacturer recommends considering alternate treatments or cisplatin dose reductions for patients with baseline renal impairment or who develop significantly reduced CrCl during cisplatin treatment. The following adjustments have been recommended.
Kintzel 1995:
CrCl 46 to 60 mL/minute: Administer 75% of dose.
CrCl 31 to 45 mL/minute: Administer 50% of dose.
CrCl ≤30 mL/minute: Consider use of alternative drug.
Krens 2019:
Therapy with curative intent: Initial dose:
GFR 50 to 59 mL/minute/1.73 m2: Administer 75% of original dose.
GFR 40 to 49 mL/minute/1.73 m2: Administer 50% of original dose.
GFR <40 mL/minute/1.73 m2: Use is not recommended.
Therapy with palliative intent: Initial dose:
GFR 50 to 59 mL/minute/1.73 m2: Administer 75% of original dose.
GFR <50 mL/minute/1.73 m2: Use is not recommended.
Bladder cancer (neoadjuvant treatment): CrCl >50 to <60 mL/minute: Split-dose cisplatin (35 mg/m2 on days 1 and 2) has been reported as an option in one study (Plimack 2014).
Hemodialysis: If the intent of therapy is curative, may consider an initial dose of 50% of the original dose (Krens 2019). Administer cisplatin following dialysis session or on nondialysis days (Janus 2010). If the intent of therapy is palliative, the use of cisplatin is not recommended (Krens 2019).
CAPD: Administer 50% of dose (Aronoff 2007).
CRRT: Administer 75% of dose (Aronoff 2007).
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 (Krens 2019).
(For additional information see "Cisplatin: Pediatric drug information")
Note: 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 (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]).
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/m2on 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: IV:
Continuous IV infusion:
Infants and Children <10 kg: PLADO regimen: 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 (Pritchard 2000)
Children ≥10 kg and Adolescents:
Monotherapy: Standard risk: 80 mg/m2/day continuous infusion over 24 hours every 2 weeks on day 1
Combination therapy: PLADO regimen: 80 mg/m2/day continuous infusion over 24 hours on day 1 of a 21-day cycle in combination with doxorubicin (Perilongo 2004; Perilongo 2009; Pritchard 2000) or doxorubicin and sorafenib (Schmid 2012)
Intermittent infusion (over 6 hours):
Infants and Children <10 kg: 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 or continuous infusion doxorubicin (Douglass 1993; Malogolowkin 2008; Ortega 2000)
Children ≥10 kg and Adolescents: 90 mg/m2 over 6 hours on day 1 of a 21-day cycle for 4 to 8 cycles in combination with vincristine and fluorouracil or continuous infusion doxorubicin (Douglass 1993; Malogolowkin 2008; Ortega 2000)
Medulloblastoma: Limited data available: Children ≥3 years and Adolescents: IV: 75 mg/m2 every 6 weeks on either day 0 in combination with vincristine and cyclophosphamide or day 1 in combination with lomustine and vincristine of each chemotherapy cycle for 8 cycles (Packer 2006; Packer 2013)
Medulloblastoma/PNET, 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) (Kim 2013)
Neuroblastoma, high-risk: Limited data available: Infants, Children, and Adolescents: IV: 50 mg/m2 on days 0 to 3 of a 21-day cycle in combination with etoposide (cycles 3 and 5) (Kreisman 2013; Naranjo 2011) or 50 mg/m2 on days 1 to 4 in combination with etoposide (cycles 3, 5, and 7) (Kushner 1994)
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 (Goorin 2003) or 120 mg/m2/day at weeks 0, 5, 12, and 17 in combination with doxorubicin (Meyers 2005)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: 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: All patients:
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
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.
Refer to adult dosing. Select dose cautiously and monitor closely; patients ≥65 years of age may be more susceptible to nephrotoxicity and peripheral neuropathy.
ASCO Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]).
Consider alternative treatments or dose reductions for toxicities.
Hematologic toxicity: May require treatment interruption and/or dosage reduction.
Hypersensitivity: Discontinue cisplatin immediately (and manage appropriately) for severe hypersensitivity reactions; do not rechallenge with cisplatin in patients with a history of severe hypersensitivity reactions.
Neurotoxicity: Consider discontinuing cisplatin if symptomatic grade 3 or 4 peripheral neuropathy develops.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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
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 (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). 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 (Armstrong 2006).
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 (Ener 2004).
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 (ESMO/EONS [Perez Fidalgo 2012]).
Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]).
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).
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).
Bladder cancer, advanced: Treatment of advanced bladder cancer
Ovarian cancer, advanced: Treatment of advanced ovarian cancer
Testicular cancer, advanced: Treatment of advanced testicular cancer
Adrenocortical carcinoma (advanced); Anal carcinoma, squamous cell (metastatic); Biliary tract cancer (advanced); Brain metastases (due to breast or non-small cell lung cancers); Breast cancer (triple-negative); Cervical cancer; Endometrial carcinoma (recurrent, metastatic, or high-risk); Esophageal cancer; Gastric cancer; Gestational trophoblastic neoplasia (high-risk); Head and neck cancer (locally advanced or metastatic disease); Hodgkin lymphoma; Malignant pleural mesothelioma; Multiple myeloma; Neuroendocrine tumors (metastatic carcinoma); Non-Hodgkin lymphoma (relapsed/refractory); Non-small cell lung cancer; Osteosarcoma; Pancreatic cancer (locally advanced or metastatic); Penile cancer (metastatic); Primary CNS lymphoma (relapsed or refractory); Prostate cancer, castration-resistant (metastatic); Small cell lung cancer (extensive-stage disease); Small cell lung cancer (limited-stage disease); Thymic carcinoma (locally advanced or metastatic); Thymomas (advanced or metastatic); Unknown primary, adenocarcinoma; Unknown primary, squamous cell carcinoma
CISplatin may be confused with CARBOplatin, oxaliplatin
Platinol may be confused with Patanol
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Cisplatin doses >100 mg/m2 once every 3 to 4 weeks are rarely used and should be verified with the prescriber.
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
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Cisplatin may cause severe myelosuppression; fatalities due to infection (secondary to myelosuppression) have been reported. Monitor blood counts (prior to cisplatin initiation, prior to each subsequent treatment course, and as clinically indicated). May require treatment interruption. Fever has been reported in patients with neutropenia. Monitor closely for signs/symptoms of infection (during and after cisplatin treatment). Geriatric patients may be at higher risk for hematologic toxicity. Hematologic toxicity may require dosage modification.
• 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: [US Boxed Warning]: 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). Monitor for hypersensitivity reactions. Ensure supportive equipment and medications for management of severe hypersensitivity reactions are available. Discontinue cisplatin immediately (and manage appropriately) for severe hypersensitivity reactions. Do not rechallenge with cisplatin in patients with a history of severe hypersensitivity reactions. 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: [US Boxed Warning]: 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); monitor renal function and electrolytes. Consider dose reductions or alternative treatments in patients with renal impairment. 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. Monitor serum creatinine, blood urea nitrogen, creatinine clearance, and serum electrolytes (calcium, magnesium, potassium, and sodium) prior to treatment initiation and as clinically indicated. Magnesium supplementation may be indicated. According to clinical treatment guidelines, consider alternate treatments or cisplatin dose reductions for patients with baseline renal impairment or who develop significantly reduced creatinine clearance during cisplatin treatment.
• Neurotoxicity: [US Boxed Warning]: 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. Perform a neurological examination prior to cisplatin initiation, as appropriate during therapy, and following completion of cisplatin therapy. Consider discontinuing cisplatin if symptomatic peripheral neuropathy develops. 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. Consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin. 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). Pediatric patients should receive audiometric testing at baseline, prior to each dose, and for several years after discontinuing therapy. An international grading scale (SIOP Boston scale) has been developed to assess ototoxicity in children (Brock 2012). In a randomized phase 3 study in pediatric patients with hepatoblastoma (standard risk) receiving cisplatin, a single dose of sodium thiosulfate (STS [brand name Pedmark]) was administered following each cisplatin dose; compared to a control group that did not receive STS, patients in the group receiving STS had a lower incidence of hearing loss and similar 3-year event-free survival and overall survival (Brock 2018).
• 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:
• Elderly: Select dose cautiously and monitor closely in elderly 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.
None known.
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
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). 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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. 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). Risk C: Monitor therapy
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: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. 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
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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. 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
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
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. 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
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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of 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 Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
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 (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
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
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
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
Verify pregnancy status prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for 14 months after the last cisplatin dose. Male patients with female partners of reproductive potential 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.
Cisplatin has been reported to cross the human placenta.
Cisplatin may cause fetal harm if administered to a pregnant female. 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.
Cisplatin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Some products may contain sodium.
Monitor blood counts (prior to cisplatin initiation, prior to each subsequent treatment course, and as clinically indicated). Monitor serum creatinine, BUN, CrCl, and serum electrolytes (calcium, magnesium, potassium, and sodium) prior to treatment initiation and as clinically indicated. Consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin (pediatric patients should receive audiometric testing at baseline, prior to each dose, and for several years after discontinuing therapy). Perform a neurological examination prior to cisplatin initiation, as appropriate during therapy, and following completion of cisplatin therapy. Monitor for hypersensitivity reactions. Monitor for signs/symptoms of infection (during and after cisplatin treatment), neuropathy, ocular toxicity, and secondary malignancies. Monitor infusion site during administration.
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
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%)
Solution (CISplatin Intravenous)
50 mg/50 mL (per mL): $0.37 - $0.87
100 mg/100 mL (per mL): $0.23 - $0.48
200 mg/200 mL (per mL): $0.43 - $0.60
Solution (reconstituted) (CISplatin Intravenous)
50 mg (per each): $600.00
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