title: RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck.
abstract: OBJECTIVE
  Patients with recurrent squamous cell cancer of the head and neck (SCH&N) are generally treated with systemic chemotherapy. Improvement in survival 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
  The eligibility requirements included SCH&N presenting as a second primary or recurrence > or =6 months after definitive RT to > or =45 Gy, with > or =75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by > or =6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m2 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 delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia 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 site without thrombocytopenia. With a median follow-up of 16.3 months for living 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 patients 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 recurrence (p = 0.083).
  
  
  CONCLUSIONS
  Repeated RT with concurrent chemotherapy as given in this study is a feasible approach for selected, previously irradiated patients with SCH&N and may produce increased median and 1-year survival rates compared with systemic chemotherapy trials reported in the literature. A randomized study should be conducted to compare these two different approaches.
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA. sspencer@uabmc.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Spencer
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: R H
authors.initials: RH
authors.lastname: Wheeler
authors.forename: M
authors.initials: M
authors.lastname: Machtay
authors.forename: C
authors.initials: C
authors.lastname: Schultz
authors.forename: W
authors.initials: W
authors.lastname: Spanos
authors.forename: M
authors.initials: M
authors.lastname: Rotman
authors.forename: R
authors.initials: R
authors.lastname: Meredith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D005472:Fluorouracil; D006918:Hydroxyurea