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 5βflourouracil (5βFU), hydroxyurea (HU), and reirradiation (RT).
Method.
Bolus 5βFU was escalated from 300mg/m^2^/d to a 10βhour infusion beginning at midnight, increased at 150 mg/m^2^/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 1βweek 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 5βFU MTD of 900 mg/m^2^/d. The seventh cohort received continuous RT and 5βFU, 750 mg/m^2^/d, one dose level below the MTD. Two hematologic, three skin, and six mucosal β₯ grade 3 toxicities were noted in 7 of 16 patients. The median survival was 10.2 months and the 1βyear survival was 41%. The median survival for the entire group was 9.4 months, with a 1β and 2βyear survival of 39% and 15%, respectively.
Conclusion.
RT can be given in a continuous fashion with concurrent 5βFU and HU. Because radiation sensitization should be achievable at nontoxic doses of 5βFU, we recommend 600 mg/m^2^/d in phase a II setting. Β© 2003 Wiley Periodicals, Inc. Head Neck 25: 118β122, 2003