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

Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):979-87. doi: 10.1016/s0360-3016(97)00121-1.

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 serious (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-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.

Conclusion: The inclusion of MMC in these chemoradiation protocols for LACC is associated with significant enhancement in serious late bowel toxicity.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Clear Cell / radiotherapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / administration & dosage
  • Carcinoma, Adenosquamous / drug therapy
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Adenosquamous / radiotherapy
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Cohort Studies
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Intestinal Diseases / chemically induced
  • Intestinal Diseases / etiology*
  • Middle Aged
  • Mitomycin / adverse effects*
  • Neoplasm Staging
  • Radiation Injuries / etiology*
  • Radiotherapy Dosage
  • Retrospective Studies
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Mitomycin
  • Fluorouracil