Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck

Michael T. Milano, Daniel J. Haraf, Kerstin M. Stenson, Mary Ellyn Witt, Cathy Eng, Bharat B. Mittal, Athanassios Argiris, Harold Pelzer, Mark F. Kozloff, Everett E. Vokes

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Purpose: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients. Experimental Design: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m2/d, for 5 days; paclitaxel, 100 mg/m2 on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50-300 mg/m2 on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade ≥4 neutropenia or thrombocytopenia for >4 days; grade ≥4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed. Results: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m2 during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m2 delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common. Conclusions: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

Original languageEnglish (US)
Pages (from-to)4922-4932
Number of pages11
JournalClinical Cancer Research
Volume10
Issue number15
DOIs
StatePublished - Aug 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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