MITOXANTRONE COMBINED WITH PACLITAXEL AS SALVAGE THERAPY FOR PLATINUM-REFRACTORY OVARIAN-CANCER - LABORATORY STUDY AND CLINICAL PILOT TRIAL

This report describes preclinical and early clinical investigations of the mitoxantrone/paclitaxel combination (NT) for patients with platin um-refractory ovarian cancer, The preclinical activity of NT was studi ed ex vivo, evaluating native tumor specimens with the ATP tumor chemo sensitivity assay, Of 24 tumors tested, 20 (83%) were sensitive to NT, whereas 7 (29%) responded to mitoxantrone and 8 (33%) responded to pa clitaxel, In the majority of tumors assayed (19 of 24), potentiating o r major independent effects between both agents were found, Subsequent ly, a clinical pilot trial of NT was initiated for patients with plati num-refractory ovarian cancer, Patients had failed one to four (median , two) prior chemotherapy regimens. In 11 cases, NT was administered e very three weeks with 8 mg/m(2) mitoxantrone and 180 mg/m(2) paclitaxe l (NT-I), Seven patients were treated biweekly with 6 mg/m(2) mitoxant rone and weekly with 100 mg/m(2) paclitaxel (NT-II), During 92 NT cour ses, myelosuppression with leucopenia, anemia, and thrombocytopenia wa s the limiting toxicity, occurring more frequently with NT-II, No pati ent required hospitalization due to any life-threatening complication, Five complete and nine partial remissions were observed with both NT- I and NT-II, accounting for an overall 78% response rate, with a media n progression-free survival of 40 weeks, One patient showed early prog ression during therapy, Currently, three patients (NT-I, two; NT-II, o ne) have died due to progressive relapsed ovarian cancer, so that the median overall survival is not reached after a median follow-up of 40. 5+ weeks, Both schedules were found to be equal in terms of response r ate and overall survival, NT is highly active and practical for salvag e treatment of ovarian cancer, NT-II may be preferred due to both clin ical activity and patients' acceptance, However, NT-I seems to be a le ss myelotoxic alternative. Both schedules warrant further clinical inv estigation.