PHASE-II STUDY OF CI-980 (NSC-635370) IN PATIENTS WITH PREVIOUSLY TREATED ADVANCED SOFT-TISSUE SARCOMAS

Doxorubicin and ifosfamide are the two most active agents in the treat ment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore , important to identify newer drugs with activity against this disease . CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin an d blocks cell cycle progression in mitosis. Given its broad spectrum a ctivity against several solid tumor models in vivo, we decided to perf orm a phase 2 study of this drug in previously treated soft-tissue sar comas. A total of 18 eligible and evaluable patients were entered in t he first stage of the trial. The median age was 53 yrs (range, 17-72). No objective responses have been noted. Six patients had stable disea se after a median of 3.5 cycles of chemotherapy while 12 others had pr ogressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m(2)/d x 3). The median AGC nadir was 1.2/mu I (0.1-4.7) on day 10 and the median platelet nadir was 150,000/mu 1(31,000-338,000). Twenty cycles were complicated with grade 3-4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade I thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one c ycle. In conclusion, CI-980 was well tolerated at this dose and schedu le but inactive in soft-tissue sarcomas.