THERAPEUTIC EFFICACY OF CAMPTOTHECIN DERIVATIVES AGAINST HUMAN-MALIGNANT MELANOMA XENOGRAFTS

Camptothecin (CPT) and some of its derivatives are currently used in s everal clinical studies with patients bearing leukaemias, lymphomas, a nd malignancies of various solid tissues. Therefore, it is important t o establish parameters and conditions that will allow the drugs to exh ibit maximal anti-cancer effectiveness with minimal toxic effects. We tested several water-insoluble CPT derivatives for their ability to in hibit growth of human melanoma tumours xenografted in nude mice. We fo und that anti-tumour effectiveness and drug-induced toxicity depended on (a) the CPT derivative; (b) the drug dose administered; (c) the mod e of administration; and (d) the scheduling of drug administration. Fo r all practical purposes, oral administration of the CPT derivative, 9 -nitrocamptothecin, has produced the best overall results.