High-dose teniposide for refractory malignancies: a phase I study.

To evaluate the dose-limiting toxicity of teniposide (VM-26), a phase I study was conducted. VM-26, a semisynthetic podophyllotoxin derivative, was administered on 3 consecutive days. The initial total dose per course was 0.3 g/m2, with dose escalation to 0.6 and 1 g/m2. The most prominent side effects observed were severe skin rash in all three patients in the highest dose group and a dose-dependent degree of leukocytopenia and thrombocytopenia. In the highest dose group the leukocyte count in all courses was less than 1 X 10(9) cells/L and in three of five courses the platelet count was less than 25 X 10(9) cells/L. Of the 13 evaluable patients, five had partial remission, one had minor response, and four had stable disease. Further study should be centered on phase II studies in selected tumor groups at a VM-26 dose of 0.6 g/m2.