A phase I-II study of concomitant chemoradiotherapy with paclitaxel (one-hour infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating factor support for patients with poor prognosis head and neck cancer

Background: Concomitant chemoradiotherapy is an effective treatment modality for advanced head and neck cancer, but improved regimens are needed. We sought to define the toxicities, recommended phase II dose, and outcome of a combination chemotherapy regimen with concomitant hyperfractionated radiotherapy in patients with poor prognosis cancers of the head and neck, including those having received prior curative intent radiotherapy. Patients and methods: From 1995 until 1997, 54 patients were treated, 25 of whom had received a prior full course of radiotherapy to the head and neck. Patients were treated with 5-fluorouracil (5-FU) 600 mg/m(2)/day continuous infusion x 5 days (days 1-5), hydroxyurea, 500 mg p.o. bid x 11 doses (days 1-6) and paclitaxel (60-150 mg/m(2)) by one-hour infusion on day 2 using a dose escalation strategy. Radiotherapy was given concomitantly on days 2-6, 150 cGy bid. Each of 4-5 cycles was delivered every other week. Results: The MTD of paclitaxel was 100 mg/m(2). The regimen was feasible; radiotherapy was delivered at a median of 7300 cGy and 83% of patients received greater than or equal to 80% planned dose intensity. Hematological toxicity, with granulocyte colony stimulating factor, was very mild. Dose limiting toxicities were mucositis and dermatitis. Despite poor prognosis, two-year survival was 45%. Conclusions: The recommended phase II dose of this regimen is 5-FU 600 mg/m(2)/day x 120 hours (days 1-5), hydroxyurea 500 mg p.o. b.i.d. x 11 doses (days 1-6), paclitaxel 100 mg/m(2) over one hour on day 2, and radiotherapy 150 cGy b.i.d. days 2-6. Concomitant chemotherapy and re-irradiation was feasible on this protocol and resulted in long-term survival in patients without other curative intent options.