Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: A randomized phase III trial of the international atomic energy agency (IAEA)

Purpose: To find the fastest and most effective/efficient method to economi cally deliver fractionated half-body irradiation (HBI) for widespread (WS), symptomatic, metastatic bone cancer. Methods and Materials: A Phase III tr ial with 3 HBI arms: (Arm A) Control (15 Gy/5 fractions/5 days); (Arm B) Hy perfractionation (HF) (8 Gy/2 fractions/1 day); (Arm C) Accelerated HF (12 Gy/4 fractions/2 days). Six countries randomized 156 patients (all with WS bone metastases): 51, 56, and 49 patients to Arms A, B, and C, respectively . There were 72 (46%) breast, 50 (32%) prostate, 9 (6%) lung, and 25 (16%) miscellaneous primary tumors. Initial performance status (PS) was 1-2 in 10 1 (65%) and PS 3-4 in 55 (35%). The lower, upper, and middle halves of the body were treated 79, 68, and 9 times. Results: Pain relief was seen in 91% of patients (45% complete [CR] and 46% partial [PR]) within 3-8 days. Over all (OS), median (MST), and pain-free (PFS) survival was 174, 150, and 122 days. Breast tumors had a higher OS (279 days) than that of other primary t umors, but when analyzed by treatment, was not significantly different than prostate tumors in Arm A. No survival differences were found in patients w ith PS 1-2 vs. 3-4, CR vs. PR, bone with/without visceral metastases, or by the number of metastases (< or > 15 bone lesions). Quality of life (QOL) a ssessed by the percent of the remaining life free of pain was 71%; furtherm ore significant improvements in PS, pain, and narcotic scores were seen aft er HBI. Toxicity was very acceptable (41% none, 50% mild/moderate, 12% seve re but transitory); more was seen with upper HBI. Conclusion: In terms of r esponse, time to response, OS, R;IST, PFS, QOL, and toxicity, schedules for Arms A and C were similar for all but prostate primaries. Schedule for Arm B, which delivered the lowest biologic dose in the shortest time, had sign ificantly worse results in pain relief, OS, MST, PFS, and QOL. Results indi cate that, for most primary tumor types (except prostate), delivering two H BI daily doses of 3 Gy in 2 consecutive days is as effective as delivering a daily dose of 3 Gy for 5 consecutive days. Thus, this is a faster and muc h more convenient HBI schedule for the palliation of pain in widespread can cer. (C) 2001 Elsevier Science Inc.