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

Cisplatin Dosing and Administration for Cancer Treatment

Cisplatin must be administered by slow intravenous infusion over 6-8 hours with mandatory pretreatment hydration of 1-2 liters infused for 8-12 hours prior to dosing, diluted in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37.5 g of mannitol. 1

Critical Administration Requirements

Never administer cisplatin by rapid intravenous injection. 1 The following safety protocols are mandatory:

• Avoid aluminum-containing needles or IV sets as aluminum reacts with cisplatin causing precipitate formation and loss of potency 1
• Maintain adequate hydration and urinary output for 24 hours following administration 1
• Do not dilute cisplatin in 5% Dextrose Injection alone 1

Disease-Specific Dosing Regimens

Head and Neck Cancer (Concurrent Chemoradiotherapy)

The standard regimen is cisplatin 100 mg/m² every 3 weeks for 3 cycles, representing the highest-quality evidence-based approach. 2 This is the ASCO-recommended standard for definitive concurrent chemoradiotherapy. 2

• A cumulative dose of ≥200 mg/m² is critical for efficacy, as patients receiving <200 mg/m² have significantly worse overall survival 2
• Alternative weekly dosing: 40 mg/m² for 6-7 weeks is acceptable with comparable efficacy but potentially improved tolerability 2
• For cisplatin-ineligible patients, carboplatin AUC 5-6 every 3 weeks is the strongest alternative 2, 3

Testicular Cancer

Administer 20 mg/m² IV daily for 5 days per cycle in combination with other chemotherapeutic agents. 1 The standard regimens include:

• BEP regimen: Etoposide 100 mg/m² IV days 1-5, cisplatin 20 mg/m² IV days 1-5, bleomycin 30 units IV weekly on days 1,8, and 15, repeated every 21 days 4
• EP regimen: Etoposide 100 mg/m² IV days 1-5, cisplatin 20 mg/m² IV days 1-5, repeated every 21 days 4

Ovarian Cancer

For metastatic ovarian cancer in combination therapy, use 75-100 mg/m² IV per cycle once every 4 weeks. 1 Two distinct approaches exist:

Intravenous Regimen:

• Paclitaxel 175 mg/m² IV over 3 hours followed by carboplatin AUC 5-6 IV over 1 hour on day 1, repeated every 3 weeks for 6 cycles 4

Intraperitoneal Regimen (for optimally debulked stage III disease):

• Paclitaxel 135 mg/m² IV continuous infusion over 24 hours on day 1, cisplatin 75-100 mg/m² IP on day 2, paclitaxel 60 mg/m² IP on day 8, repeated every 3 weeks for 6 cycles 4, 5
• This IP regimen demonstrated a 16-month overall survival advantage (65.6 vs 49.7 months) 5
• Only 42% of patients complete all 6 cycles due to toxicity, requiring aggressive hydration and often outpatient IV fluids for 5-7 days after each cycle 5

Bladder Cancer

Administer 50-70 mg/m² IV per cycle once every 3-4 weeks as a single agent. 1 Dosing considerations:

• For heavily pretreated patients, use initial dose of 50 mg/m² per cycle repeated every 4 weeks 1
• Dose depends on extent of prior radiation therapy and/or chemotherapy 1

Non-Small Cell Lung Cancer (Adjuvant Setting)

Use cisplatin 50 mg/m² on days 1 and 8 every 4 weeks for 4 cycles combined with vinorelbine 25 mg/m² weekly for 16 weeks. 2

• Median administered dose is often only 84% of maximum intended due to compliance challenges 2

Thymomas and Thymic Carcinomas

First-line CAP regimen: Cisplatin 50 mg/m² IV day 1, doxorubicin 50 mg/m² IV day 1, cyclophosphamide 500 mg/m² IV day 1, administered every 3 weeks 4

Second-line PE regimen: Cisplatin 60 mg/m² IV day 1, etoposide 120 mg/m² IV days 1-3 4

Safety Monitoring and Repeat Dosing Criteria

Do not administer repeat courses until ALL of the following criteria are met: 1

• Serum creatinine <1.5 mg/100 mL
• BUN <25 mg/100 mL
• Platelets ≥100,000/mm³
• WBC ≥4,000/mm³
• Audiometric analysis confirms auditory acuity within normal limits

Dose-Limiting Toxicities

Nephrotoxicity is the dose-limiting side effect for cisplatin. 6 Other significant toxicities include:

• Ototoxicity requiring audiometric monitoring 1, 6
• Myelosuppression (leukopenia, neutropenia, thrombocytopenia, anemia) 6
• Neurotoxicity 6
• Severe nausea and vomiting requiring antiemetic prophylaxis 6
• Hepatotoxicity 6

Common Pitfalls to Avoid

• Never exceed 100 mg/m² per cycle without careful consideration - FDA labeling specifically warns pharmacists to call prescriber if dose exceeds this threshold 1
• Do not substitute carboplatin for cisplatin in the perioperative setting for bladder cancer, as evidence does not support this substitution 4
• Do not use cetuximab as a substitute for platinum agents in definitive concurrent chemoradiotherapy for head and neck cancer 3
• For patients with borderline renal function, consider split-dose administration (35 mg/m² on days 1 and 2 or days 1 and 8), though relative efficacy remains undefined 4

Storage and Stability

• Store at 20-25°C (68-77°F); do not refrigerate 1
• Protect unopened container from light 1
• After initial entry, cisplatin in amber vial is stable for 28 days protected from light or 7 days under fluorescent room light 1
• If diluted solution is not used within 6 hours, protect from light 1