Cumulative Cisplatin Dose in Definitive Concurrent Chemoradiation (CRT) for Head and Neck Squamous Cell Carcinoma (HNSCC)

Key Concept:
- Threshold:
  - ≥ 200 mg / m² cumulative cisplatin dose during a standard 6 to 7 week course of definitive radiation:
    - Is the best-validated benchmark for improved locoregional control (LRC), disease-free survival (DFS), and overall survival (OS)

Why It Matters:
- Tumor Control:
  - Falling short of ~ 200 mg / m² increases risk of locoregional failure and distant metastasis
- Plateau Effect:
  - Doses >240 to 300 mg /m² do not add survival benefit:
    - But raise nephrotoxicity, ototoxicity, neuropathy
Practical Application:
- Standard q3-weekly:
  - 100 mg / m² IV day 1, 22, 43 → planned 300 mg / m² :
    - Goal ≥ 200 mg / m² even if 3rd cycle omitted
- Weekly regimen (most common alternative):
  - 40 mg / m² weekly × 6 to 7 → target 240 to 280 mg / m²
  - Critical pearl:
    - At least 5 full cycles (~ 200 mg /m²) must be delivered:
      - Less than 5 cycles carries inferior outcomes in multiple series
Key Tips:
- Assess eligibility carefully:
  - Baseline creatinine clearance ≥ 60 mL / min, no grade ≥ 2 hearing loss, etc.
- Supportive care:
  - Aggressive hydration, Mg / K replacement, antiemetics to avoid dose reductions or delays
References:L
- Staar S, et al. J Clin Oncol. 2001;19:861-869.
- Pignon JP, et al. MACH-NC Collaborative Group. Radiother Oncol. 2009;92:4-14.
- Ang KK, et al. J Clin Oncol. 2014;32:2940-2948.
- Bauml JM, et al. J Clin Oncol. 2019;37:1987-1994.
- NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 2025.

Bottom line:
- For definitive HNSCC chemoradiation:
  - Achieve ≥ 200 mg / m² total cisplatin:
    - Regardless of dosing schedule:
      - To maintain the survival advantage demonstrated in pooled analyses and contemporary RTOG data

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO