New vinca alkaloids and related compounds.

The vinca alkaloids remain among the most useful classes of anticancer agents used in the clinic today. However, previous analogs of these agents have not realized either increased safety or an enhanced antitumor spectrum. Currently, three derivatives are in clinical trial: vinorelbine, vintripol, and vinxaltine. Vinorelbine has shown consistent antitumor activity in patients with breast carcinoma and is in phase III trials in the United States, Europe, and Japan. Vintripol and vinxaltine, vinca alkaloids conjugated to amino acids, are in early clinical trials in Europe. The dose-limiting toxicity of these agents is leukopenia. A similar agent with a different chemical structure, rhizoxin, is in early phase II clinical trials with initial activity noted in breast carcinoma. The ultimate role of these agents in treatment of human malignancy awaits the results of ongoing studies.