ROLE OF MITOMYCIN-C IN THE DEVELOPMENT OF LATE BOWEL TOXICITY FOLLOWING CHEMORADIATION FOR LOCALLY ADVANCED-CARCINOMA OF THE CERVIX

Purpose: To determine if the inclusion of mitomycin C (MMC) in chemora diation protocols for locally advanced cervical cancer (LACC) signific antly enhances the development of serious (Grade 3) late bowel toxicit y (SLBT), Methods and Materials: The incidence of SLBT in 154 patients with LACC entered in six consecutive chemoradiotherapy protocols betw een February 1982 and June 1987 was determined. Fifty-four patients wh o were treated with MMC, 5-fluorouracil (5-FU), and radiation were com pared to 100 patients who received similar treatment without MMC. Univ ariate and multivariate analyses assessed the effect of the following parameters on the development of SLBT: (a) external beam dose, (b) rec tal and rectosigmoid dose, (c) paraaortic radiation, (d) intracavitary dose and dose rate, (e) volume of tissue irradiated to a total dose o f 60 Gy, (f) International. Federation of Gynecology and Obstetrics st age, (g) age, (h) number of courses of 5-FU, (i) previous abdominopelv ic surgery, (j) split versus continuous radiation, and (k) administrat ion of MMC. Results: The overall incidence of SLBT was 15.6%: 14 of 54 (26%) versus 10 of 100 (10%) for patients who did or did not receive MMC, respectively (p = 0.009), Multivariate analysis revealed the admi nistration of MMC as the only factor predictive for the development of SLBT (p = 0.012, odds ratio = 3.15; 95% confidence interval 1.3-7.7), A significant reduction in SLBT was observed with the elimination of MMC from the chemoradiation protocols despite dose escalation of both radiation and 5-FU. No increase in overall survival was observed in pa tients receiving MMC, 5-FU, and radiation compared with 5-FU and radia tion alone. Conclusion: The inclusion of MMC in these chemoradiation p rotocols for LACC is associated with significant enhancement in seriou s late bowel toxicity, (C) 1997 Elsevier Science Inc.