Phase 1 trial of combined chemotherapy and reirradiation for recurrent unresectable head and neck cancer

Abstract

Background. The management of recurrent unresectable head and neck cancer remains a challenging problem. Based on the circadian rhythm concept, we sought to determine the maximum tolerated dose (MTD) of infusional 5‐flourouracil (5‐FU), hydroxyurea (HU), and reirradiation (RT). Method. Bolus 5‐FU was escalated from 300mg/m²/d to a 10‐hour infusion beginning at midnight, increased at 150 mg/m²/d increments. HU, 1.5 g, remained constant. Chemotherapy was given on weeks 1 and 4. RT was given daily, 2.0 Gy per fraction on weeks 1 and 2 followed by a 1‐week break, then hyperfractionated weeks 4 and 5, total dose 50 Gy. The goal was to deliver a continuous course of RT to 60 Gy after the MTD was determined with an additional week of chemotherapy. Results. Six cohorts were treated to establish the 5‐FU MTD of 900 mg/m²/d. The seventh cohort received continuous RT and 5‐FU, 750 mg/m²/d, one dose level below the MTD. Two hematologic, three skin, and six mucosal ≥ grade 3 toxicities were noted in 7 of 16 patients. The median survival was 10.2 months and the 1‐year survival was 41%. The median survival for the entire group was 9.4 months, with a 1‐ and 2‐year survival of 39% and 15%, respectively. Conclusion. RT can be given in a continuous fashion with concurrent 5‐FU and HU. Because radiation sensitization should be achievable at nontoxic doses of 5‐FU, we recommend 600 mg/m²/d in phase a II setting. © 2003 Wiley Periodicals, Inc. Head Neck 25: 118–122, 2003