High Dose vs Low Dose Cisplatin in Concurrent Chemoradiation for Locally Advanced Head and Neck Squamous Cell Carcinomas

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • ConCERT Phase III Trial (ASCO 2022):
    • Design:
      • Randomized, multicenter, definitive treatment of locally advanced HNSCC
    • Findings:
      • Weekly 40 mg/m² was non-inferior to 100 mg/m² every 3 weeks in 2-year locoregional control:
        • 60.9% vs 57%, within a 10% non-inferiority margin
      • Better tolerance:
        • Fewer severe toxicities
        • Fewer hospitalizations
        • Fewer treatment interruptions with the weekly regimen
      • No significant differences in OS or PFS after ~ 26 months follow-up
  • Earlier Small Randomized and Retrospective Studies:
    • Tsan et al. (2012) (Phase III, ~ 55 patients):
      • 100 mg/m² every 3 weeks had higher compliance (more patients achieved ≥ 200 mg/m² cumulative dose) and lower acute toxicity than weekly 40 mg/m²
    • Mashhour et al. (2020):
      • Compared weekly 30 mg/m² vs 100 mg/m² every 3 weeks:
        • Weekly arm:
          • Less acute toxicity
          • Improved compliance
          • However, loco‑regional control was lower in weekly arm (57.6% vs 72.8%)
    • Singh et al. (2022, retrospective):
      • 3‑weekly arm achieved better OS and DFS, higher completion of cumulative dose:
        • But had more toxicities and treatment breaks
    • Meta‑Analysis and Cumulative Dose Importance
      Pooled analysis (Canada / Italy):
      • Higher cumulative cisplatin exposure (≥ 200 mg/m²) correlated with significantly better overall survival, especially in HPV-negative HNSCC:
        • 3-year OS:
          • 72% vs 60% vs 52%, p < 0.001
    • Ongoing and Investigational Trials:
      • NRG‑HN009 (Phase II/III, recruiting):
        • Comparing toxicity and non-inferiority in OS between weekly 40 mg/m² vs 100 mg/m² every 3 weeks, stratified by HPV status
      • CISLOW Trial (Netherlands, protocol published 2023):
        • Focuses on patients with low skeletal muscle mass, comparing compliance and
          Cisplatin Dose-Limiting Toxicity (CDLT) risk between weekly and triweekly regimens
      • Fractionated cisplatin schedules (2024) are also being explored, e.g., splitting 100 mg/m² over 4 days to improve tolerability
  • Bottom Line (as of August 2025):
    • High-dose (100 mg/m² q 3weeks):
      • Remains the standard based on long-term efficacy, especially where achieving ≥ 200 mg /m² is feasible and toxicities can be managed
    • Weekly 40 mg/m² has emerged as a viable alternative:
      • Not inferior in locoregional control per ConCERT, with better tolerability, particularly for patients with comorbidities or reduced treatment tolerance
    • Maintaining an adequate cumulative cisplatin dose (≥ 200 mg/m²) is crucial for optimal oncologic outcomes
  • Ongoing randomized trials (e.g., NRG-HN009, CISLOW) should provide clearer guidance soon
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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