SUPPOSITORY ADMINISTRATION OF CHEMOTHERAPEUTIC DRUGS WITH CONCOMITANTRADIATION FOR RECTAL-CANCER

Citation
Rm. Pokorny et al., SUPPOSITORY ADMINISTRATION OF CHEMOTHERAPEUTIC DRUGS WITH CONCOMITANTRADIATION FOR RECTAL-CANCER, Diseases of the colon & rectum, 40(12), 1997, pp. 1414-1420
Citations number
15
Categorie Soggetti
Gastroenterology & Hepatology",Surgery
ISSN journal
00123706
Volume
40
Issue
12
Year of publication
1997
Pages
1414 - 1420
Database
ISI
SICI code
0012-3706(1997)40:12<1414:SAOCDW>2.0.ZU;2-C
Abstract
PURPOSE: Preoperative radiation with combined chemotherapy is effectiv e in shrinking advanced rectal cancer locally and facilitating subsequ ent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenou s administration. This prompted us to evaluate suppository and intrave nous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, l ymph node, and lung tissue and systemic and portal blood were collecte d serially from male Sprague Dawley rats to determine drug concentrati ons following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment g roups and received 5-fluorouracil suppositories, mitomycin C supposito ries, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 da ys following this treatment, blood was collected, colonoscopy was perf ormed, and rectal tissue was harvested for histologic examination. RES ULTS: Mitomycin C suppository was significantly less toxic compared wi th intravenous de livery, 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 suppositor y and radiation resulted in additive myelosuppression at day 6 (P < 0. 05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C s uppository delivery combined with radiation causes less systemic toxic ity and is more effective than intravenous administration.