Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy

J. L. Lefebvre, F. Rolland, M. Tesselaar, E. Bardet, C. R. Leemans, L. Geoffrois, P. Hupperets, L. Barzan, D. De Raucourt, D. Chevalier, L. Licitra, F. Lunghi, R. Stupp, D. Lacombe, J. Bogaerts, J. C. Horiot, J. Bernier, J. B. Vermorken

Research output: Contribution to journalArticlepeer-review

236 Scopus citations

Abstract

Background: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. Methods: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. Results: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. Conclusions: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalJournal of the National Cancer Institute
Volume101
Issue number3
DOIs
StatePublished - Feb 2009

Funding

Cancer trial registry number for this trial is NCT00002839 . This publication was supported by grants 2U10 CA11488-25 through 5U10 CA11488-37 from the National Cancer Institute (Bethesda, MD) . This research project was supported by Fonds Cancer/FOCA (Belgium) .

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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