Platinum-based chemotherapy plus cetuximab in head and neck cancer

Jan B. Vermorken, Ricard Mesia, Fernando Rivera, Eva Remenar, Andrzej Kawecki, Sylvie Rottey, Jozsef Erfan, Dmytro Zabolotnyy, Heinz Roland Kienzer, Didier Cupissol, Frederic Peyrade, Marco Benasso, Ihor Vynnychenko, Dominique De Raucourt, Carsten Bokemeyer, Armin Schueler, Nadia Amellal, Ricardo Hitt

Research output: Contribution to journalArticle

1839 Citations (Scopus)

Abstract

Background: Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. Methods: We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. Results: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P = 0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P = 0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths. Conclusions: As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.).

Original languageEnglish
Pages (from-to)1116-1127
Number of pages12
JournalNew England Journal of Medicine
Volume359
Issue number11
DOIs
Publication statusPublished - Sep 4 2008

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vermorken, J. B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., Erfan, J., Zabolotnyy, D., Kienzer, H. R., Cupissol, D., Peyrade, F., Benasso, M., Vynnychenko, I., De Raucourt, D., Bokemeyer, C., Schueler, A., Amellal, N., & Hitt, R. (2008). Platinum-based chemotherapy plus cetuximab in head and neck cancer. New England Journal of Medicine, 359(11), 1116-1127. https://doi.org/10.1056/NEJMoa0802656