RTOG 96-10: Reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck

Purpose: Patients with recurrent squamous cell cancer of the head and neck (SCH&N) are generally treated with systemic chemotherapy. Improvement in su rvival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. Methods and Materials: The eligibility requirements included SCH&N presenti ng as a second primary or recurrence greater than or equal to6 months after definitive RT to greater than or equal to 45 Gy, with greater than or equa l to 75% of the tumor volume within the previous field. The cumulative spin al cord dose was limited to 50 Gy, and measurable disease was required. Fou r weekly cycles were given, each separated by 1 week of rest. A cycle consi sted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, w ith the fractions separated by greater than or equal to6 h, with 1.5 g of h ydroxyurea given 2 h and 300 mg/m(2) of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. Results: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were deliver ed in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and G rade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 ne utropenia. occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor s ite without thrombocytopenia. With a median follow-up of 16.3 months for li ving patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patient s treated within 3 years (p = 0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurren ce (p = 0.083). Conclusion: Repeated RT with concurrent chemotherapy as given in this study is a feasible approach for selected, previously irradiated patients with S CH&N and may produce increased median and 1-year survival rates compared wi th systemic chemotherapy trials reported in the literature. A randomized st udy should be conducted to compare these two different approaches. (C) 2001 Elsevier Science Inc.