RANDOMIZED PHASE I II TRIAL OF 2 VARIANTS OF ACCELERATED FRACTIONATEDRADIOTHERAPY REGIMENS FOR ADVANCED HEAD AND NECK-CANCER - RESULTS OF RTOG-88-09/

Purpose: To establish the feasibility of performing split-course accel erated hyperfractionation (AHFX-S) and concomitant boost accelerated f ractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the t umor clearance rate and acute and late toxicity of these fractionation schedules. Methods and Materials: Between February 1989 and January 1 990, 75 patients with Stage III or IV squamous cell carcinoma of the h ead and neck were randomized to receive: (a) AHFX-S: 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy; or (b) AFX-C: 1. 8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 week s to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment;during the last 11 treatment days, to a total d ose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were sc ored according to the RTOG normal tissue reaction scales and tumor cle arance was evaluated at completion of therapy and at regular intervals thereafter. Results: Of the 70 analyzable patients, 38 received AHFX- S and 32 received AFX-C. The two arms were balanced with respect to se x, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX -C arm. The median follow-up was 2 years (range: 0.03-4.87 years). Tol erance of both variants of accelerated fractionated radiotherapy was s atisfactory. There was no significant difference in local-regional con trol, disease-free survival, or survival between the two arms. The 2-y ear local-regional failure rate, survival, and disease-free survival w as 50, 50, and 40%, respectively, for the entire group of patients. Ac ute radiation mucositis was increased in both arms. There was no signi ficant difference in the incidence of grade 3 acute toxicities (63% vs . 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxiciti es. Permanent grade 4 late toxicity was observed in 6 and 7% of the pa tients, respectively. Conclusion: Results of this randomized Phase I/I I trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, loca l-regional control, disease-free survival, or survival in this small s cale study. Therefore, a Phase III trial comparing the relative effica cy of these two accelerated fractionation schedules against standard f ractionation and hyperfractionation has been activated.