Published in:
01-03-2013 | Original Paper
Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer
Authors:
Joseph I. Clark, Joshua B. Greene, Ann Lau Clark, Jay S. Dalal, Craig C. Hofmeister
Published in:
Medical Oncology
|
Issue 1/2013
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Abstract
Platinum-based therapy is active in advanced head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis; many have difficulty tolerating cisplatin-based regimens. Oxaliplatin has antitumor activity without many of the toxicities of cisplatin. We conducted a phase I pilot study to investigate the dose limitation of oxaliplatin with 5-fluorouracil (5-FU) and cetuximab in patients with untreated recurrent or metastatic HNSCC. The planned dose escalation schedule included: dose level 1: oxaliplatin 100 mg/m2 day 1, 5-FU CIV 750 mg/m2/day over 96 h beginning day 1, and cetuximab 400 mg/m2 day 1 (then 250 mg/m2 weekly) every 21 days. Dose level 2: oxaliplatin 130 mg/m2 day 1, 5-FU CIV 1,000 mg/m2/day over 96 h beginning day 1, and the same dose and schedule of cetuximab. Seven patients were accrued at dose level 1 and three at dose level 2. Dose level 1 toxicity included grade 1–2 stomatitis, fatigue, acneiform rash, and anemia, and grade 1 nausea and transaminitis. Dose level 2 toxicity was unacceptable: 2 of 3 patients experienced grade 4 toxicities (stomatitis, diarrhea, and acute renal failure) requiring hospitalization with one treatment-related death. Accrual was therefore closed with dose level 1 considered the maximum tolerated dose. Observed responses were short-lived. The regimen of oxaliplatin 100 mg/m2 day 1, infusional 5-FU 750 mg/m2/day over 96 h beginning day 1, and cetuximab 400 mg/m2 day 1 (then 250 mg/m2 weekly), every 21 days, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment for unresectable or metastatic HNSCC.