PACLITAXEL DELIVERED AS A 3-HR INFUSION WITH CISPLATIN IN PATIENTS WITH GYNECOLOGIC CANCERS - UNEXPECTED INCIDENCE OF NEUROTOXICITY

In an effort to develop a paclitaxel plus cisplatin combination chemot herapy regimen which can be easily employed in the outpatient setting, 38 patients (median age, 59; range, 39-72) with gynecological maligna ncies (20 ovarian; 6 primary peritoneal; 12 endometrial) seen at the C leveland Clinic Foundation from June 1993 to May 1995 were administere d 170 cycles of paclitaxel (135 or 175 mg/m(2)) over 3 hr followed by cisplatin (starting dose 75 mg/m(2)). Of the 33 patients with elevated CA-125 levels prior to the initiation of chemotherapy, all experience d >50% decreases in this antigen level, while 23/33 (70%) had >90% red uctions. In general, nonneurologic side effects were mild in severity and easily manageable, Unfortunately, 71% of the patients developed ne urologic toxicity, with one-fifth of the treated population experienci ng severe neurotoxic side effects (grade 3-4). We conclude that paclit axel administered over 3 hr at a dose of 135 or 175 mg/m(2), followed by cisplatin (75 mg/m(2)), is a highly active regimen in gynecologic m alignancies. Unfortunately, in our experience, the incidence and sever ity of neurotoxicity with this regimen is considerably greater than th at reported with paclitaxel administered over 24 hr in combination wit h cisplatin, As a result of the observed toxicity profile, this drug d elivery schedule for cisplatin and paclitaxel cannot be recommended fo r general clinical use. (C) 1996 Academic Press, Inc.