Comparative antitumour activity of vinblastine-isoleucinate and related vinca alkaloids in human tumour xenografts

Abstract

The antitumour activity of the investigational agent vinblastine-isoleucinate (V-LEU) was compared with vintriptol, another investigational agent of the same series of vinblastine-23-oyl amino acid derivatives, and vinblastine, their clinically active parent compound, in a panel of nine human tumour xenografts growing subcutaneously in nude mice. Compounds were administered intravenously at equitoxic doses twice weekly. As assessed by optimal tumour growth inhibition and tumour growth delay, vinblastine, V-LEU and vintriptol exhibited antitumour activity in 8/9, 7/9 and 4/7 human tumour xenografts, respectively. When growth curves and numbers of complete remissions were compared, V-LEU was the most active agent in two malignant melanoma lines (THXO and LOX p28) and two small cell lung carcinoma lines tested (LXFS 538 and WX 322), whereas vinblastine was more active against the two colorectal carcinomas (CXF 243 and CXF 280). Notably, the non small cell lung carcinoma (NSCLC) line AHXOL was resistant to the three agents. The results of this study suggest that V-LEU was as active as vinblastine in most tumour lines, exhibiting superior antitumour activity in malignant melanoma, SCLC and breast cancer lines. The decision to bring this compound into clinical trial shall await further confirmation of these preclinical results and the evaluation of its toxicity profile in relation to other vinca alkaloids.