Weekly vs q3-Weekly Cisplatin with Definitive Radiation (RT)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Bottom line: 
    • q3-weekly 100 mg / m² has strongest legacy evidence for tumor control:
      • Weekly 40 mg / m² is used in practice:
        • But superiority isn’t proven in definitive settings
  • Post-operative exception: 
    • JCOG1008 (high-risk post-op):
      • Showed weekly 40 mg / m² non-inferior to q3-weekly for OS with less renal / ototoxicity
  • Use on exam: 
    • If the stem is definitive CRT and asks “preferred” or “most evidence-based,”:
      • Pick q3-weekly
    • If post-op high-risk:
      • Weekly is acceptable / non-inferior
  • Numbers: 
    • Many programs target ≥ 200 mg / m² cumulative regardless of schedule
  • Definitive CRT (unresected locally advanced head and neck SCC (LA-HNSCC):
    • Benchmark regimen:
      • High-dose cisplatin 100 mg/m² q3 weeks ×3 during standard-fractionation RT:
        • Remains the legacy standard for tumor control and survival:
          • Based on multiple RCTs and meta-analyses:
            • Most reviews still treat this as the reference arm in trials PMC
    • Weekly 30 mg / m² vs q3-weekly 100 mg / m² (inferior control):
      • The randomized Tata Memorial Trial:
        • Noronha et al., JCO 2018:
          • n=300:
            • Mostly adjuvant CRT:
              • But often extrapolated to definitive:
                • Tested 30 mg / m² weekly vs 100 mg/m² q3-weekly
          • Two-year locoregional control was:
            • 58.5% (30 mg / m²) vs 73.1% (q3w 100 mg / m²):
              • HR for LRF 1.76 (95% CI 1.11–2.79)
          • Acute grade ≥ 3 toxicity was lower with weekly:
            • 71.6% vs 84.6%
          • OS was similar at that follow-up:
            • HR 1.14; P=.48
        • Takeaway: 
          • Weekly 30 mg / m² is inferior for LRC PubMed
  • Weekly 40 mg / m²vs q3-weekly 100 mg / m² (emerging / definitive setting):
    • The ConCERT phase III trial (India; definitive CRT):
      • Reported non-inferiority of weekly 40 mg / m² to q3-weekly 100 mg / m² for LRC and OS:
        • With fewer severe AEs, fewer RT interruptions and hospitalizations in the weekly-40 mg / m² arm
      • Interim 2-yr LRC rates were:
        • ~ 61.5% (weekly 40 mg / m²) vs 57.7% (q3w 100 mg / m²):
          • Absolute difference + 3.8% within the non-inferiority margin (NI margin)
      • Full peer-reviewed primary publication is pending:
  • Adherence and cumulative dose matter:
    • Real-world and retrospective datasets show patients on q3-weekly more often achieve ≥ 200 mg / m² cumulative cisplatin:
      • 75.6% q3-weekly vs 47.1% weekly:
        • Median cumulative 200 mg / m² vs 160 mg / m²
      • Missing several weekly cycles correlates with worse survival
      • This is one reason many programs “aim for ≥ 200 mg / m²” regardless of schedule PMCJAMA Network
  • What to pick on exams: 
    • If a stem asks for the “preferred / most evidence-based” regimen for definitive CRT:
      • Choose cisplatin 100 mg / m² q3 weeks:
        • Cite weekly 40 mg / m² only if the question explicitly frames it as acceptable or references ConCERT-like criteria PMC
  • Post-operative high-risk CRT (positive margin and / or ENE):
    • JCOG1008 (phase II / III, JCO 2022):
      • In resected high-risk HNSCC:
        • Weekly 40 mg / m² was non-inferior to q3-weekly 100 mg / m² for overall survival: 
          • HR 0.69 (99.1% CI 0.374–1.273) at the pre-specified interim:
            • The updated analysis maintained NI (HR 0.75; 95% CI 0.50–1.13)
        • Key toxicity deltas favored weekly dosing:
          • Grade ≥ 3 neutropenia 35% vs 49%
          • Infection 7% vs 12%
          • Renal impairment (any grade) 30% vs 40%
          • Hearing impairment (any grade) 7% vs 17%
          • Grade 4 AEs 8.2% vs 18.6%:
            • Two treatment-related deaths occurred in the weekly arm
        • Practical implication: 
          • Weekly 40 mg / m² is an evidence-based option post-op high risk patients PMC+1
  • Cumulative dose “≥ 200 mg/m²”: what’s the evidence?:
    • The classic systematic review (Strojan et al., Head & Neck 2016):
      • Supports an association between ≥ 200 mg/m² and better outcomes during CRT:
        • Which has driven the common “≥ 200 mg / m²” target PubMed
    • Not all cohorts confirm a strict threshold effect:
      • Swiss multicenter series didn’t reproduce a survival break at 200 mg/m²:
        • But more patients reach ≥ 200 mg m² on q3-weekly than weekly in multiple real-world datasets
    • Nuance:
      • In HPV-positive disease:
        • Dose–outcome relationships may be flatter except in T4 / N3 subsets
    • Bottom line for boards:
      • ≥ 200 mg/m² is a reasonable target, and shortfall—especially with missed weekly cycles—tracks with worse outcomes PMCScienceDirect
  • Put it all together:
    • Definitive CRT: 
      • “Cisplatin 100 mg m² q3 weeks is the preferred / most established regimen for tumor control
      • Weekly 40 mg / m² is used widely:
        • ConCERT suggests non-inferiority with better tolerability:
          • But full publication is pendin:
            • So for test stems asking ‘preferred,’ pick q3-weekly.”
      • Aim for ≥ 200 mg/m² cumulativePMCThe ASCO Post
    • Post-op high-risk: 
      • “Weekly 40 mg / m² is non-inferior to q3-weekly for OS with less renal / ototoxicity(JCOG1008)”:
        • It’s acceptable to choose weekly in these stems PMC
  • Numbers to memorize:
    • Noronha 2018 (weekly 30 mg / m² vs q3w 100 mg / m²): 
      • 2-yr LRC 58.5% vs 73.1%
        • HR LRF 1.76:
          • Inferior weekly-30 mg/m²
      • Acute ≥ G3 toxicity:
    • ConCERT (definitive, weekly 40 mg / m² vs q3w 100 mg / m²): 
    • JCOG1008 (post-op high-risk): 
      • OS HR 0.69 (NI) at interim
      • Renal impairment 30% vs 40% and hearing impairment 7% vs 17% (weekly vs q3w) PubMedPMC
    • Cumulative dose: 
      • Many datasets target ≥ 200 mg/m²:
        • q3-weekly more often reaches that level:
          • ~76% vs ~47%weekly:
            • Missing weekly cycles worsens outcomes PMC
  • Refs: JCOG1008 (JCO 2022); Noronha 2018; guideline synopses.
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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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