Originally published as JCO Early Release 10.1200/JCO.2005.04.3547 on May 22 2006

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Phase I/II Study of Cetuximab in Combination With Cisplatin or Carboplatin and Fluorouracil in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Jean Bourhis, Fernando Rivera, Ricard Mesia, Ahmad Awada, Lionel Geoffrois, Christian Borel, Yves Humblet, Antonio Lopez-Pousa, Ricardo Hitt, M. Eugenia Vega Villegas, Lionel Duck, Dominique Rosine, Nadia Amellal, Armin Schueler, Andreas Harstrick

From the Institut Gustave Roussy, Villejuif; Centre Alexis Vautrin, Vandoeuvre les Nancy; Centre Paul Strauss, Strasbourg, France; Hospital Universitario Marqués de Valdecilla, Santander; Institut Català d’Oncologia, Duran I Reynals, L’Hospitalet; Hospital de la Sant Creu i de Sant Pau, Barcelona; Hospital Universitario de Octubre, Madrid, Spain; Institut Jules Bordet; University Hospital Saint-Luc, Brussels, Belgium; and Merck KGaA, Darmstadt, Germany

Address reprint requests to Jean Bourhis, MD, PhD, Institut Gustave Roussy, Radiothérapie, 39 rue Camille Desmoulins, 94800 Villejuif, France; e-mail: bourhis{at}igr.fr

PURPOSE: This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS: Treatment comprised cetuximab (initial dose 400 mg/m² with subsequent weekly doses of 250 mg/m²) in combination with 3-week cycles of either cisplatin (100 mg/m²) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m²/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.

RESULTS: Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics.

CONCLUSION: The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m²/d in combination with cisplatin or carboplatin can be recommended for additional studies.

Presented as preliminary results at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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