PHASE-II STUDY OF IV CL-980 IN PATIENTS WITH ADVANCED PLATINUM REFRACTORY EPITHELIAL OVARIAN-CARCINOMA

CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the c olchicine site, inhibiting the polymerization of microtubules and arre sting cellular division in metaphase. Myelosuppression and neurotoxici ty were dose-limiting in phase I studies. Sixteen patients with stage III and IV platinum-refractory ovarian cancer received 4.5 mg/m(2)/day of CI-980 as a continuous i.v. infusion for 72 h, repeated every 3 we eks. Eleven patients had progression and four patients had stable dise ase. One patient (6%; 95% CI 0-25%) achieved a partial response after 9 months of treatment which lasted for 27 months. The overall median s urvival was 7 months. Grade 4 granulocytopenia occurred in five patien ts, with two episodes of neutropenic fever. Neurological toxicity was mild with 12 episodes of transient subclinical recent memory loss docu mented in four patients by specialized neuropsychological evaluations. One patient each had hallucinations and mild truncal ataxia, and four patients had mild, reversible neurosensory toxicity. One episode of s evere hypoxemia and dyspnea occurred in a patient with chronic obstruc tive pulmonary disease. CI-980 has minimal activity and is tolerable i n a population of heavily pretreated patients with platinum refractory ovarian cancer. [(C) 1998 Lippincott-Raven Publishers.].