Phase II and Pharmacologic Study of Weekly Oral Paclitaxel Plus Cyclosporine in Patients With Advanced Non–Small-Cell Lung Cancer

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Abstract
PURPOSE: A phase II study was performed to assess the efficacy and toxicity of oral cyclosporine (CsA) plus paclitaxel in advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive or previously treated patients (one regimen) with measurable disease and World Health Organization performance status ≤ 2 were eligible. Oral paclitaxel was given weekly in a dose of 90 mg/m2 bid. CsA (10 mg/kg) was given 30 minutes before each dose of oral paclitaxel. RESULTS: Twenty-six patients with a median age of 54 years (range, 32 to 77 years) were entered onto this study. Eighteen patients (69%) had received one prior chemotherapy regimen. The most frequently recorded toxicities were as follows: National Cancer Institute common toxicity criteria grade 3 neutropenia, eight patients (31%); grade 4, six patients (23%); grade 4 febrile neutropenia, three patients (12%); grade 2/3 neurotoxicity, three patients (12%); and grade 2 nail changes, four patients (15%). The overall response rate (ORR) of the 23 assessable patients was 26% (95% confidence interval [CI], 10% to 48%). In the intention-to-treat population, the ORR was 23% (95% CI, 9% to 44%). The median time to progression was 3.5 months (95% CI, 1.2 to 3.9 months), and median overall survival was 6.0 months (95% CI, 2.3 months to not available). Pharmacokinetics revealed that the mean area under the concentration-time curve (AUC) of oral paclitaxel was 5.0 ± 2.3 μmol/L/h in week 1 and 4.6 ± 2.0 μmol/L/h in week 2, with interpatient variabilities (coefficient of variation [%CV]) of 45% and 42%, respectively. The intrapatient variability (%CV) of the AUC was 14.5%. CONCLUSION: Oral paclitaxel plus CsA is active and safe in advanced NSCLC, including in patients previously treated with chemotherapy.