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
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.