A RANDOMIZED TRIAL OF STANDARD VERSUS PARTIALLY HYPERFRACTIONATED RADIATION WITH OR WITHOUT CONCURRENT 5-FLUOROURACIL IN LOCALLY ADVANCED CERVICAL-CANCER

The objective of this study was to determine whether the addition of c oncurrent 5-fluorouracil (5-FU) and/or a change in radiation fractiona tion improves pelvic control and survival or decreases complications i n advanced cervical cancer, FIGO stages IB/IIA (greater than or equal to 5 cm) to IVA inclusive. After stratification by pelvic disease exte nt, 234 of a planned 292 patients were randomized to receive one of fo ur possible treatments: (a) standard external beam pelvic irradiation (RT) 5000 cGy in 25 fractions versus (b) RT as in arm (a) with infusio nal IV 5-FU 1g/m(2) daily in the first and last 4 days of RT, (c) part ially hyperfractionated RT, 5280 cGy in 33 fractions, two fractions pe r day on the first and last 4 days of RT, or (d) arm (c) with the same FU. All were followed with a linear source of intracavitary RT to del iver 40 Gy. The median duration of follow-up for the 221 evaluable pat ients was 59 months. The 5-year Kaplan-Meier disease-free survival (DF S) in arm (a), (c), (d), and (b), respectively, were 45, 53, 58, and 6 1%. The differences in survival and pelvic control were not statistica lly significant. An exploratory subset analysis was performed within s tratum 1 and stratum 2 to generate hypotheses for future studies. Only for the 99 patients in stratum 1 (IB/IIA or medial parametrial IIB di sease) was the 5-year DFS significantly better (long rank P = 0.05) fo r standard RT and 5-FU. The DFS was 39% for arm (a), 76% for arm (b), 58% for arm (c), and 65% for arm (d). A multivariate analysis of patie nt, tumor, and treatment related prognostic factors identified only th e use of 5-FU to account for the observed difference. The crude seriou s late bowel or bladder complication rate was 5.9%. Overall concurrent infusional 5-FU was not beneficial when added to standard RT in this study. The possible benefit for patients in stratum 1 requires explora tion in a further randomized trial with appropriate accrual. (C) 1998 Academic Press.