Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer.

Published

Journal Article

PURPOSE: Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination. RESULTS: Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P < 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P < 0.05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.

Full Text

Duke Authors

Cited Authors

  • Pokorny, RM; Wrightson, WR; Lewis, RK; Paris, KJ; Hofmeister, A; LaRocca, R; Myers, SR; Ackerman, D; Galandiuk, S

Published Date

  • December 1997

Published In

Volume / Issue

  • 40 / 12

Start / End Page

  • 1414 - 1420

PubMed ID

  • 9407977

Pubmed Central ID

  • 9407977

International Standard Serial Number (ISSN)

  • 0012-3706

Language

  • eng

Conference Location

  • United States