Role of mitomycin C in the development of late bowel toxicity following chemoradiation for locally advanced carcinoma of the cervix.
OBJECTIVE
To determine if the inclusion of mitomycin C (MMC) in chemoradiation protocols for locally advanced cervical cancer (LACC) significantly enhances the development of serious (Grade 3) late bowel toxicity (SLBT).


METHODS
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-fluorouracil (5-FU), and radiation were compared 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 rectosigmoid dose, (c) paraaortic radiation, (d) intracavitary dose and dose rate, (e) volume of tissue irradiated to a total dose of 60 Gy, (f) International Federation of Gynecology and Obstetrics stage, (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.


CONCLUSIONS
The inclusion of MMC in these chemoradiation protocols for LACC is associated with significant enhancement in serious late bowel toxicity.
Rakovitch
E
E
Department of Radiation Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Canada.
Fyles
A W
AW
Pintilie
M
M
Leung
P M
PM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced / Q000209:etiology*; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects*; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D016685:Mitomycin; D005472:Fluorouracil