EXTRAVASATION INJURY POTENTIAL OF CI-980, A NOVEL SYNTHETIC MITOTIC INHIBITOR

Severe soft-tissue ulceration is known to result from inadvertent extr avasation of a number of anticancer drugs, including tubulin-binding v inca alkaloids, during intravenous administration. CI-980 is a novel a nticancer drug candidate that also inhibits mitosis by binding to tubu lin. Intradermal administration of CI-980 to mice at doses of 0.02 and 0.05 mg produced ulcerative lesions in 3/5 and 2/5 animals, respectiv ely, that were significantly smaller than those produced in all animal s at vinblastine doses of 0.05 and 0.1 mg. Ulcerative lesions resultin g from CI-980 treatment were also less persistent, resolving in 2-8 da ys versus 7-16 days following vinblastine administration. As based on the common dose of 0.05 mg, CI-980 appears to have significantly less vesicant activity than vinblastine.