Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with gynecologic cancers: unexpected incidence of neurotoxicity

Abstract

In an effort to develop a paclitaxel plus cisplatin combination chemotherapy regimen which can be easily employed in the outpatient setting, 38 patients (median age, 59; range, 39-72) with gynecological malignancies (20 ovarian; 6 primary peritoneal; 12 endometrial) seen at the Cleveland Clinic Foundation from June 1993 to May 1995 were administered 170 cycles of paclitaxel (135 or 175 mg/m2) over 3 hr followed by cisplatin (starting dose 75 mg/ m2). Of the 33 patients with elevated CA-125 levels prior to the initiation of chemotherapy, all experienced > 50% decreases in this antigen level, while 23/33 (70%) had > 90% reductions. In general, nonneurologic side effects were mild in severity and easily manageable. Unfortunately, 71% of the patients developed neurologic toxicity, with one-fifth of the treated population experiencing severe neurotoxic side effects (grade 3-4). We conclude that paclitaxel administered over 3 hr at a dose of 135 or 175 mg/m2, followed by cisplatin (75 mg/m2), is a highly active regimen in gynecologic malignancies. Unfortunately, in our experience, the incidence and severity of neurotoxicity with this regimen is considerably greater than that reported with paclitaxel administered over 24 hr in combination with cisplatin. As a result of the observed toxicity profile, this drug delivery schedule for cisplatin and paclitaxel cannot be recommended for general clinical use.