Vindesine in the Therapy of Solid Tumors

SummaryThe Vinca alkaloids have been used extensively in cancer chemotherapy. We have been involved in the evaluation of the new Vinca alkaloid, vindesine, since the early Phase I trials. Our Phase I trial indicated that a dose of 4-5 mg/m2 every 10–14 days was appropriate. Subsequently, we also evaluated a continous infusion schedule of 1.2 mg/m2/day x5 days every 3 weeks. Modest, but definite activity was found in colorectal carcinoma, and vindesine has been incorporated into combination regimes for this disease. Three of 9 patients with esophageal carcinoma achieved objective responses. The continuous infusion schedule of vindesine was used in non-oat cell carcinoma of the lung but this schedule did not offer any advantages. An effective regimen has been the combination of vindesine, adriamycin and plational, which produced a 33 % response rate among 83 patients. Eight of 22 patients with melanoma have achieved objective responses as have 4 of 12 patients with renal cell carcinoma. Hematological toxicity has been limited primarily to neutropenia with a platelet-sparing effect. Other toxicities have included nausea, vomiting, constipation and paresthesias. Vindesine is a useful drug for treating some solid tumors. Its lesser toxicity makes it easier to administer for prolonged periods than vincristine. Also, cross-resistance does not always exist among the Vinca alkaloids, and some patients who are refractory to the other agents will respond to vindesine.