Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovariancarcinoma: A gynecologic oncology group study

Purpose: A phase II study was conducted to determine the efficacy of paclit axel and valspodar (PSC 833) in patients with advanced epithelial ovarian c ancer. Valspodar, a nonimmunosuppressive cyclosporine D analogue that rever ses P-glycoprotein-mediated multidrug resistance, in combination with pacli taxel might be active in paclitaxel-resistant and refractory ovarian cancer . Patients and Methods: Patients received valspodar 5 mg/kg orally qid x 12 d oses, paclitaxel (70 mg/m(2) intravenously for 3 hours) was administered on day 2, 2 hours after the fifth or sixth dose of valspodar. This treatment was repeated every 21 days. One blood sample was collected before the sixth dose of valspodar for the first three cycles to evaluate valspodar trough concentration. Tumor tissue was obtained from patients for immunohistochemi cal staining of P-glycoprotein, Results: Of 60 patients entered, 58 were assessable for response. There wer e five partial responses (8.6%; 90% confidence interval [CI], 3.8 to 20.0; median duration of response, 5.0 months [range, 1.9 to 10.5 months]). Media n progression-free survival was 1.5 months (90% CI, 1.4 to 2.4), Grade 3 or 4 toxicities observed were neutropenia, anemia, nausea and vomiting, perip heral neuropathy, and cerebellar ataxia, The trough concentrations of valsp odar were greater than or equal to 1,000 ng/mL in all but two of 40 patient s in the first cycle. Immunohistochemical staining for p-glycoprotein was p ositive for one of two responding patients. Conclusion: Valspodar in combination with paclitaxel has limited activity i n patients with paclitaxel-resistant ovarian carcinoma. An international ra ndomized clinical trial of paclitaxel and carboplatin with or without valsp odar as first-line therapy in advanced ovarian cancer is underway. J Clin O ncol 19:2975-2982, (C) 2001 by American Society of Clinical Oncology.