What is the recommended dosage and administration of Cisplatin for cancer treatment?

Cisplatin Dosing and Administration for Cancer Treatment

Standard Dosing by Cancer Type

The recommended cisplatin dosage varies significantly by cancer type and treatment regimen, ranging from 20 mg/m² daily for 5 days in testicular cancer to 100 mg/m² every 3-4 weeks as monotherapy for ovarian or bladder cancer. 1

FDA-Approved Indications and Doses

Testicular Cancer:

• 20 mg/m² IV daily for 5 days per cycle in combination with other chemotherapeutic agents 2, 1
• Administered as part of the BEP regimen (bleomycin, etoposide, cisplatin) every 21 days 2

Ovarian Cancer:

• Combination therapy: 75-100 mg/m² IV per cycle once every 4 weeks (Day 1) with cyclophosphamide 1
• Single agent: 100 mg/m² IV per cycle once every 4 weeks 1
• Intraperitoneal route: 75-100 mg/m² IP on Day 2 following IV paclitaxel for optimally debulked stage III disease 2, 3

Bladder Cancer:

• 50-70 mg/m² IV per cycle once every 3-4 weeks as a single agent 2, 1
• For heavily pretreated patients: initial dose of 50 mg/m² per cycle repeated every 4 weeks 2, 1

Other Common Cancer Regimens

Nasopharyngeal Carcinoma:

• Concurrent with radiotherapy: 100 mg/m² triweekly (or at least 80 mg/m²) OR 40 mg/m² weekly 2
• Target cumulative dose of at least 200 mg/m² (3 doses triweekly or 7 doses weekly) 2
• Induction chemotherapy: 60-80 mg/m² on day 1 every 3 weeks for 2-3 cycles in combination regimens 2

Thymoma/Thymic Carcinoma:

• CAP regimen: 50 mg/m² IV day 1 every 3 weeks with doxorubicin and cyclophosphamide 2
• Second-line PE regimen: 60 mg/m² IV day 1 with etoposide 2

Head and Neck Cancer:

• Concurrent with radiotherapy: 100 mg/m² triweekly or 40 mg/m² weekly 2
• Cumulative dose ≥200 mg/m² associated with significantly improved overall survival 2

Critical Administration Requirements

Hydration Protocol (Mandatory):

• Pre-treatment: 1-2 liters of fluid infused for 8-12 hours prior to cisplatin dose 1
• During infusion: Dilute cisplatin in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37.5 g mannitol 1
• Infusion time: 6-8 hours (NEVER give as rapid IV injection) 1
• Post-treatment: Maintain adequate hydration and urinary output for 24 hours following administration 1

Critical Safety Precautions:

• Never use needles or IV sets containing aluminum parts—aluminum reacts with cisplatin causing precipitate formation and loss of potency 1
• Do not dilute cisplatin in 5% Dextrose Injection alone 1
• Protect diluted solution from light if not used within 6 hours 1

Eligibility Criteria and Contraindications

Renal Function Requirements:

• Do not administer repeat courses until serum creatinine <1.5 mg/100 mL and/or BUN <25 mg/100 mL 1
• Cisplatin ineligibility typically defined as creatinine clearance <60 mL/min 2
• For borderline renal function, split-dose administration (35 mg/m² on days 1 and 2 or days 1 and 8) may be considered, though efficacy is undefined 2

Hematologic Requirements:

• Do not give repeat courses until platelets ≥100,000/mm³ and WBC ≥4,000/mm³ 1

Ototoxicity Monitoring:

• Subsequent doses should not be given until audiometric analysis confirms auditory acuity is within normal limits 1
• Grade ≥2 hearing loss or tinnitus is a common contraindication 2

Other Contraindications:

• Grade ≥2 peripheral neuropathy 2
• ECOG performance status >2 2
• Recent cardiac dysfunction (unstable angina, myocardial infarction, or NYHA class III heart failure within 3 years) 2

Common Pitfalls and Management Strategies

Dosing Errors:

• Pharmacists should call prescriber if dose exceeds 100 mg/m² per cycle to prevent inadvertent overdosage 1
• Only 38-42% of patients complete full planned cisplatin doses in some studies due to toxicity 2, 3

Carboplatin Substitution:

• Carboplatin should NOT be substituted for cisplatin in the perioperative or curative-intent settings—it is not equivalent 2
• Carboplatin alternatives (AUC 5-6) are only appropriate for cisplatin-ineligible patients in palliative settings 2

Cumulative Dose Threshold:

• A cumulative cisplatin dose of ≥200 mg/m² is required for optimal efficacy in concurrent chemoradiotherapy regimens 2
• If induction chemotherapy is given, the cumulative cisplatin dose needed in the concurrent phase may be reduced to 160 mg/m² based on patient tolerance 2

Alternative Platinum Agents for Ineligible Patients:

• Nedaplatin 100 mg/m² triweekly 2
• Carboplatin AUC 5-6 triweekly 2
• Oxaliplatin 70 mg/m² weekly 2
• These alternatives have intermediate evidence quality and should only be used when cisplatin is contraindicated 2

Major Toxicities Requiring Monitoring

Dose-Limiting Toxicities:

• Nephrotoxicity (dose-limiting for cisplatin) 4
• Neurotoxicity (peripheral neuropathy) 5, 4
• Ototoxicity (hearing loss, especially in younger patients) 5, 6, 4

Other Significant Toxicities:

• Myelosuppression (leukopenia, thrombocytopenia, anemia) 3, 4
• Nausea/vomiting/dehydration requiring aggressive antiemetic therapy 3, 4
• Anaphylactic-like reactions (facial edema, wheezing, tachycardia, hypotension) 1
• Hepatotoxicity (transient SGOT and bilirubin elevations) 1, 4
• Local tissue toxicity with extravasation (concentrations >0.5 mg/mL may cause cellulitis, fibrosis, necrosis) 1

Monitoring Requirements:

• Renal function (creatinine, BUN) before each cycle 1
• Complete blood counts before each cycle 1
• Audiometric testing periodically 1
• Liver function tests 4
• Electrolytes (particularly magnesium) 4