Role of mitomycin C in the development of late bowel toxicity foloowing chemoradiation for locally advanced carcinoma of the cervix

Abstract

Purpose : To determine if the inclusion of mitomycin C (MMC) in chemoradiation protocols for locally advanced cervical cancer (LACC) significantly enhances the development of serius (Grade 3) late bowel toxicity (SLBT). Methods and Materials : The incidence of SLBT in 154 patients with LACC entered in six consecutive chemoradiotherapy protocols between February 1982 and June 1987 was determined. Fifty-four patients who were treated with MMC, 5-flourouracil (5-FU), and radiation were compated to 100 patients who received similar treatment without MMC. Univariate and multivariate analyses assessed the effect of the following parameters on the development of SLBT: (a) external beam dose, (b) rectal and rectosignoid dose, (c) paraaortic radiation, (d) intracavitary dose and dose rate, (e) volume of tissue irradiated to a total dose od 60 Gy, (f) International Federation of Gynecology and Obstetrics stages, (g) age, (h) number of courses of 5-FU, (i) previous abdominopelvic surgery, (j) split versus continuous radiation, and (k) administration 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 administration 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 patients receiving MMC, 5-FU, and radiation compared with 5-Fu and radiation alone. Conclusion : The inclusion of MMC in these chemoradiation protocols for LACC is associated with significant enhancement in serious late bowel toxicity.