What is the recommended use and dosage of Cisplatin in cancer treatment?

Cisplatin in Cancer Treatment: Recommended Use and Dosage

Cisplatin is a platinum-based chemotherapeutic agent administered intravenously for multiple solid tumors and hematologic malignancies, with specific dosing protocols that vary by cancer type and treatment intent. 1

Mechanism and Clinical Applications

Cisplatin exerts its cytotoxic effect by forming DNA crosslinks with purine bases, interfering with DNA repair mechanisms and inducing apoptosis in cancer cells. 2 It is effective against carcinomas, germ cell tumors, lymphomas, and sarcomas, with established roles in testicular, ovarian, bladder, head and neck, lung, and cervical cancers. 2, 3

Specific Dosing Regimens by Cancer Type

Testicular Cancer

• Standard dose: 20 mg/m² IV daily for 5 days per cycle in combination with other chemotherapeutic agents 1
• BEP regimen (malignant germ cell tumors): Cisplatin 20 mg/m² daily for days 1-5, combined with bleomycin 30 units per week and etoposide 100 mg/m² daily for days 1-5, repeated every 21 days for 3-4 cycles 4

Ovarian Cancer

• Combination therapy: 75-100 mg/m² IV per cycle once every 4 weeks (Day 1) in combination with cyclophosphamide 600 mg/m² IV 1
• Single agent: 100 mg/m² IV per cycle once every 4 weeks 1
• Intraperitoneal regimen (Category 1 for stage III optimally debulked disease): Paclitaxel 135 mg/m² IV continuous infusion over 24 hours on Day 1, followed by cisplatin 75-100 mg/m² IP on Day 2, then paclitaxel 60 mg/m² IP on Day 8, repeated every 3 weeks for 6 cycles 4

The intraperitoneal approach demonstrated a 16-month survival advantage compared to standard IV therapy (65.6 vs 49.7 months; P=0.03) in the GOG 172 trial, though only 42% of patients completed all 6 cycles due to toxicity. 4 Using the lower IP cisplatin dose of 75 mg/m² may reduce toxicity while maintaining efficacy. 4

Bladder Cancer

• Standard dose: 50-70 mg/m² IV per cycle once every 3-4 weeks as a single agent 1
• Heavily pretreated patients: Initial dose of 50 mg/m² per cycle repeated every 4 weeks 1
• Perioperative setting: Gemcitabine and cisplatin for 4 cycles is a reasonable alternative to dose-dense MVAC based on equivalence data in advanced disease 4

Nasopharyngeal Carcinoma

• Concurrent with radiotherapy (triweekly): 100 mg/m² (or at least 80 mg/m²) once every 3 weeks, attempting 3 doses to achieve cumulative dose ≥200 mg/m² 4
• Concurrent with radiotherapy (weekly): 40 mg/m² weekly, attempting 7 doses to achieve cumulative dose ≥200 mg/m² 4
• Induction chemotherapy (GP regimen): Cisplatin 80 mg/m² on day 1 with gemcitabine 1,000 mg/m² on days 1 and 8, every 3 weeks for 3 cycles 4
• Induction chemotherapy (TPF regimen): Cisplatin 60-75 mg/m² on day 1 with docetaxel 60-75 mg/m² and 5-fluorouracil 600-750 mg/m² per day continuous infusion days 1-5, every 3 weeks for 3 cycles 4

Post hoc analyses suggest a threshold cumulative cisplatin dose of 200 mg/m² is required for efficacy in concurrent chemoradiotherapy. 4 If induction chemotherapy is given, the cumulative cisplatin dose needed in the concurrent phase is typically 160 mg/m² based on patient tolerance. 4

Thymomas and Thymic Carcinomas

• CAP regimen (preferred for thymoma): Cisplatin 50 mg/m² IV on day 1, doxorubicin 50 mg/m² IV on day 1, cyclophosphamide 500 mg/m² IV on day 1, administered every 3 weeks 4
• ADOC regimen: Cisplatin 50 mg/m² IV on day 1, doxorubicin 40 mg/m² IV on day 1, vincristine 0.6 mg/m² IV on day 3, cyclophosphamide 700 mg/m² IV on day 4, administered every 3 weeks 4
• PE regimen (second-line): Cisplatin 60 mg/m² IV on day 1, etoposide 120 mg/m² IV daily on days 1-3 4

Anal Squamous Cell Carcinoma

• With fluorouracil: Cisplatin 60 mg/m² once per day on days 1 and 29 (maximum surface area 2.0 m², max single dose 120 mg) with FU 1,000 mg/m² continuous infusion once per day on days 1-4 (week 1) and 29-32 (week 5) 4
• Alternative weekly regimen: Cisplatin 20 mg/m² IV once per week with FU 300 mg/m² infused continuously on days of radiation (lower level of evidence) 4

Administration Requirements and Safety Precautions

Mandatory Hydration Protocol

• 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 of mannitol, infused over 6-8 hours 1
• Post-treatment: Maintain adequate hydration and urinary output for 24 hours following administration 1

Critical warning: Do not dilute cisplatin in 5% Dextrose Injection alone. 1 Cisplatin should NOT be given by rapid intravenous injection—only by slow IV infusion. 1

Aluminum Precaution

Never use needles or IV sets containing aluminum parts that may contact cisplatin, as aluminum reacts with cisplatin causing precipitate formation and loss of potency. 1

Repeat Dosing Criteria

Do not administer repeat courses until: 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

Overdose Prevention

The FDA label specifically instructs pharmacists to call the prescriber if the dose exceeds 100 mg/m² per cycle. 1 Vials are imprinted with "CALL DR. IF DOSE > 100 MG/M²/CYCLE" to prevent inadvertent overdosage. 1

Dose-Limiting Toxicities and Contraindications

Nephrotoxicity is the dose-limiting toxicity for cisplatin. 5 Other significant toxicities include ototoxicity, peripheral neuropathy, myelosuppression, hepatotoxicity, and severe nausea/vomiting. 2, 6, 5

Cisplatin is contraindicated in patients with: 4

• Renal dysfunction
• Significant pre-existing neuropathy
• Hearing loss

For patients with cisplatin contraindications, alternative platinum agents include carboplatin (AUC 5-6), oxaliplatin (70 mg/m² weekly), or nedaplatin (100 mg/m² triweekly). 4 However, carboplatin should not be routinely substituted for cisplatin in the perioperative or adjuvant setting for most cancers, as current data do not support equivalent efficacy. 4

Alternative Dosing for Renal Impairment

For patients with borderline renal function or minimal dysfunction, split-dose administration of cisplatin may be considered (such as 35 mg/m² on days 1 and 2, or days 1 and 8), though the relative efficacy of such modifications remains undefined. 4

Storage and Stability

Store at 20-25°C (68-77°F); do not refrigerate. 1 Protect unopened containers from light. 1 After initial entry, cisplatin remaining in the 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