Second-line chemotherapy with cisplatin-ifosfamide in patients with ovarian cancer previously treated with carboplatin-cyclophosphamide

In an effort to use antineoplastic drug combinations which are active in pl atinum resistant ovarian cancer or which can induce a second response after a platinum first-line treatment, we conducted a study on 30 ovarian cancer patients previously treated with carboplatin plus cyclophosphamide who wer e given ifosfamide 5 g/m(2) i.v. divided over days 1 to 3 plus mesma combin ed with cisplatin 100 mg/m(2) i.v, divided over days 1. to 3 every 4 weeks as second-line treatment. Eight patients had never entered remission with f irst-line chemotherapy while 22 patients had tumor recurrence within 6 to 1 8 months after the end of chemotherapy and their tumors were considered pot entially platinum sensitive. Responding patients received 6 courses while p alliative treatment for nonresponders was provided, Of the 22 patients with tumor recurrence, 8 patients responded with one partial response (PR) and 7 complete clinical responses (CCR), Two out of the 8 patients with platinu m resistant disease demonstrated short lasting PR. Seven patients with CCR underwent second-look operation and in two a pathological CR was documented . Median time to progression was 6 mo (4-12), The median overall survival w as 12 mo (4-20), Myelotoxicity despite G-CSF administration was significant with grade 4 leukopenia in 40% and grade 3 thrombocytopenia in 20% of pati ents. Central nervous system (CNS) toxicity was significant with 30% somnol ence, 20% disorientation and an episode of grand-mal epilepsy ascribed to i fosfamide, With a 33% response rate the combination is as effective as new agents employed in relapsed ovarian cancer. Platinum-refractory disease may respond to a lesser degree. The most important determinant of response was the progression-free interval from first-line chemotherapy. Whether patien ts recurring after carboplatin plus cyclophosphamide have a greater chance to respond to cisplatin plus ifosfamide or vice-versa cannot be supported b y the current data and therefore randomized studies should be performed to this end.