par Bourhis, Jean;Rivera, Fernando;Mesia, Ricard;Awada, Ahmad ;Geoffrois, Lionel;Borel, Christian;Humblet, Yves;Lopez-Pousa, J J;Hitt, Ricardo;Vega Villegas, M Eugenia;Duck, Lionel;Rosine, Dominique;Amellal, Nadia;Schueler, Armin;Harstrick, Andreas
Référence Journal of clinical oncology, 24, 18, page (2866-2872)
Publication Publié, 2006-06
Référence Journal of clinical oncology, 24, 18, page (2866-2872)
Publication Publié, 2006-06
Article révisé par les pairs
Résumé : | 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. |