Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.

e16027 Background: Platinum-based chemotherapy including cisplatin, 5-fluorouracil (5-FU), and the EGFR-directed monoclonal antibody cetuximab, are active in the treatment of head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis and many have difficulty tolerating cisplatin-based regimens. Oxalipatin, a third-generation platinum derivative, has demonstrated antitumor activity and lacks many of the limiting side effects of cisplatin. We conducted a phase I pilot study to investigate the dose-limitation of oxaliplatin in addition to infusional 5-FU and cetuximab in patients with untreated recurrent or metastatic HNSCC. Methods: The planned dose escalation schedule included: dose level 1: oxaliplatin 100mg/m 2 day 1, 5-FU CIV 750mg/m 2 over 96 hours beginning day 1, and cetuximab 400mg/m 2 cycle 1, day 1 (and 250mg/m 2 weekly thereafter) on a 21-day cycle. Dose level 2: oxaliplatin 130mg/m 2 day 1, 5-FU CIV 1000mg/m 2 over 96 hours beginning day 1 and the same dose and schedule of cetuximab. Results: A total of 10 patients were accrued, consisting of 4 females and 6 males. The first seven were enrolled onto dose level 1 and the following three onto dose level 2. Dose level 1 was tolerated well with acceptable toxicity, including grade 1-2 oral mucositis, grade 1-2 fatigue, grade 1-2 acneiform rash, grade 1 nausea, grade 1-2 anemia and grade 1 transaminitis. All responses observed, (1 MR, 1 PR, 1 CR), were short-lived. Dose level 2 was more toxic than anticipated; 2 of 3 patients experienced grade 4 toxicities (mucositis, diarrhea, acute renal failure) requiring hospitalization with a treatment-related death in one of these patients. The phase I portion of the trial was therefore closed and dose level 1 is considered the maximum tolerated dose. Conclusions: The regimen of oxaliplatin 100mg/m 2 day 1, infusional 5-FU 750mg/m 2 over 96 hours beginning day 1, and cetuximab 400mg/m 2 cycle 1, day 1 (with 250mg/m 2 weekly thereafter), given on a 21-day cycle, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment of unresectable or metastatic HNSCC.