Source: New England Journal of Medicine, Volume 359:1116-1127, September 11, 2008, Number 11
Authors: Jan B. Vermorken, M.D., Ph.D. et al.

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)

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

Authors’ affiliations:
From Antwerp University Hospital, Edegem (J.B.V.); and Ghent University Hospital, Ghent (S.R.) — both in Belgium; Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona (R.M.); Hospital Universitario Marqués de Valdecilla, Santander (F.R.); and Hospital 12 de Octubre, Madrid (R.H.) — all in Spain; Orszagos Onkologiai Intezet, Budapest (E.R.), and Szabolcs-Szatmar Bereg Megyei Josa Andras Korh, Nyiregyhaza (J.E.) — both in Hungary; Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland (A.K.); Institute of Otolaryngology, Academy of Medical Sciences of Ukraine, Kiev (D.Z.); and Sumy Regional Oncology Center, Sumy (I.V.) — both in Ukraine; Ludwig Boltzmann Institute for Applied Cancer Research, Kaiser Franz Josef Spital, Vienna (H.-R.K.); Centre Val d’Aurelle Paul Lamarque Service d’Oncologie, Montpellier (D.C.); Centre Antoine Lacassagne, Nice (F.P.); and Centre François Baclesse, Caen (D.D.R.) — all in France; Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy (M.B.); and Universitaetskrankenhaus Hamburg-Eppendorf, Hamburg (C.B.); and Merck, Darmstadt (A.S., N.A.) — both in Germany.