Comparison of DX-8951f and topotecan effects on tumor colony formation from freshly explanted adult and pediatric human tumor cells

DX-8951f, which shows great therapeutic potential, was tested in the human tumor cloning system in adult and pediatric tumor types against which topot ecan has been active. In 47 tumors from adults, DX-8951f had definite cytot oxic activity in a concentration-dependent manner with both Ih and continuo us exposures. Topotecan was minimally effective using a 1 h exposure and sh owed concentration-dependent inhibition with continuous exposure. In head-t o-head comparisons at 1 h exposure against adult tumors, DX-8951f was signi ficantly more effective at 0.1 and 1.0 mu g/ml than topotecan, In head-to-h ead comparisons (continuous exposure), 1.0 mu g/ml DX-8951f was more effect ive than topotecan at 1.0 mu g/ml in adult tumors, including three of four head and neck, one of two kidney, two of five liver, six of 10 non-small ce ll lung, five of eight ovarian, four of eight prostate tumors, and in singl e specimens of breast, mesothelioma, colon and small cell lung tumors. With continuous exposure, DX-8951f and topotecan were equally effective at equi molar concentrations, The maximum tolerated dose for DX-8951f is 3 times th at of topotecan, so higher doses of DX-8951f could be administered to patie nts. DX-8951f is a promising new antineoplastic agent with significant acti vity against tumors taken directly from patients. [(C) 1999 Lippincott Will iams & Wilkins.].