What is the recommended dose of cisplatin (cis-diamminedichloroplatinum) for chemotherapy?

Recommended Dose of Cisplatin for Chemotherapy

The recommended dose of cisplatin varies by cancer type and treatment setting, with the most common evidence-based regimens being 100 mg/m² every 3 weeks for 3 cycles (concurrent with radiotherapy in head/neck cancer), 50 mg/m² on days 1 and 8 every 4 weeks for 4 cycles (adjuvant lung cancer), or 20 mg/m² daily for 5 days (testicular cancer). 1

FDA-Approved Dosing by Indication

The FDA label provides specific dosing for three approved indications 1:

• Metastatic Testicular Tumors: 20 mg/m² IV daily for 5 days per cycle (in combination with other chemotherapeutic agents) 1
• Metastatic Ovarian Tumors: 75-100 mg/m² IV once every 4 weeks in combination with cyclophosphamide, or 100 mg/m² as a single agent every 4 weeks 1
• Advanced Bladder Cancer: 50-70 mg/m² IV every 3-4 weeks as a single agent (50 mg/m² every 4 weeks for heavily pretreated patients) 1

Head and Neck Cancer Dosing

For definitive concurrent chemoradiotherapy in head and neck squamous cell carcinoma, cisplatin 100 mg/m² every 3 weeks for 3 cycles represents the highest-quality evidence-based standard. 2

Alternative Weekly Dosing

• Weekly cisplatin 40 mg/m² for 6-7 weeks is an acceptable alternative with comparable efficacy but potentially improved tolerability 2
• The ASCO/CSCO nasopharyngeal carcinoma guideline found no significant survival differences between weekly (40 mg/m²) and triweekly (100 mg/m²) schedules, with the weekly regimen showing improved quality of life 2
• Recent evidence suggests weekly dosing may be non-inferior for disease outcomes with significantly less toxicity 3

Cumulative Dose Threshold

A cumulative cisplatin dose of ≥200 mg/m² is critical for efficacy in concurrent chemoradiotherapy. 2 Post-hoc analyses demonstrate that patients receiving <200 mg/m² cumulative dose have significantly worse overall survival 2. When induction chemotherapy precedes concurrent chemoradiotherapy, the cumulative cisplatin dose during the concurrent phase can be reduced to approximately 160 mg/m² based on patient tolerance 2.

Adjuvant Therapy for Resected Head and Neck Cancer

For high-risk resected head and neck cancer (extracapsular nodal spread or positive margins), cisplatin 100 mg/m² every 3 weeks for 3 cycles concurrent with radiotherapy is the standard regimen. 4 An alternative of cisplatin 50 mg/m² weekly has also shown survival benefit in randomized trials 4.

Non-Small Cell Lung Cancer (Adjuvant Setting)

The ASCO/Cancer Care Ontario guideline recommends 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, based on the NCIC-CTG JBR.10 trial that demonstrated the greatest survival benefit 2. Alternative regimens from major trials include 2:

• Cisplatin 100 mg/m² every 3-4 weeks for 3-4 cycles (ALPI, ANITA trials)
• Cisplatin 80-120 mg/m² every 3-4 weeks for 3-4 cycles (IALT trial)

Carboplatin is not recommended in the adjuvant lung cancer setting as current data do not support its routine use 2.

Anal Squamous Cell Carcinoma

For concurrent chemoradiotherapy in anal cancer, cisplatin 60 mg/m² on days 1 and 29 with maximum surface area of 2.0 m² (maximum single dose 120 mg) combined with 5-fluorouracil is recommended 2. An alternative weekly regimen of cisplatin 20 mg/m² IV once weekly with continuous FU infusion is also acceptable, though based on lower-level evidence 2.

Nasopharyngeal Carcinoma Induction Regimens

For induction chemotherapy prior to concurrent chemoradiotherapy, platinum-based regimens include 2:

• GP regimen: Gemcitabine 1,000 mg/m² days 1 and 8; cisplatin 80 mg/m² day 1
• TPF regimen: Docetaxel 60-75 mg/m² day 1; cisplatin 60-75 mg/m² day 1; 5-FU 600-750 mg/m²/day continuous infusion days 1-5
• PF regimen: Cisplatin 80-100 mg/m² day 1; 5-FU 800-1,000 mg/m²/day continuous infusion days 1-5

Administration Requirements

All cisplatin regimens require mandatory pretreatment hydration with 1-2 liters of fluid infused for 8-12 hours prior to dosing. 1 The drug should be diluted in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37.5 g of mannitol and infused over 6-8 hours 1. Adequate hydration and urinary output must be maintained for 24 hours following administration 1.

Critical Safety Thresholds

Repeat courses should not be given until 1:

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

Common Pitfalls and Caveats

Never exceed 100 mg/m² per cycle without careful consideration, as the FDA label specifically warns pharmacists to contact prescribers if doses exceed this threshold 1. The vial itself is imprinted with "CALL DR. IF DOSE >100 MG/M²/CYCLE" 1.

Do not use aluminum-containing needles or IV sets, as aluminum reacts with cisplatin causing precipitate formation and loss of potency 1.

Compliance with planned dosing is frequently suboptimal. In the JBR.10 trial, the median administered dose of cisplatin was only 84% of the maximum intended 2. In head and neck cancer, approximately 40% of patients fail to complete three cycles of triweekly high-dose cisplatin 2, 3.

Cisplatin should not be given by rapid IV injection—only by slow IV infusion over 6-8 hours for standard regimens 1.

For cisplatin-ineligible patients (creatinine clearance <60 mL/min, grade ≥2 hearing loss, grade ≥2 peripheral neuropathy, or age >70-75 years with comorbidities), carboplatin AUC 5-6 every 3 weeks represents the strongest alternative for head and neck cancer 2, 5.