A Phase I/II Study of Lapatinib Plus Carboplatin and Paclitaxel in Relapsed Ovarian and Breast Cancer

Abstract Purpose Our objective was to find the maximum tolerated combination dose of daily oral lapatinib and weekly carboplatin (C) and paclitaxel (T; metronomic mCT). The secondary objectives included toxicity, safety, and efficacy of response to therapy in patients with relapsed ovarian and breast cancer previously treated with platinum chemotherapy. Patients and Methods We conducted a phase I/II study of mCT plus lapatinib in 24 patients with relapsed epithelial ovarian cancer and 6 patients with relapsed breast cancer from 2005 to 2007. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. Response was assessed using Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Results Median patient age was 57 years (range, 30–85 years), with a median of 2 previous regimens (range, 1–10 regimens). The maximum tolerated dose combination was oral lapatinib 1000 mg daily with weekly paclitaxel 60 mg/m 2 and carboplatin area under the curve of 2 each given for 3 weeks on and 1 week off. The overall response rate of the 25 evaluable patients was 44%, with 4 (16%) complete responses and 7 (28%) partial responses. Nine patients achieved stable disease (36%), with 5 experiencing progressive disease on study (20%). For patients with ovarian cancer, the estimated median PFS was 6 months (95% CI, 5–12 months), and the estimated median OS was 17 months (95% CI, 14–21 months). Conclusion This study suggests that treatment with daily oral lapatinib plus weekly mCT can be safely administered to patients with relapsed advanced ovarian or breast cancers. This treatment was well tolerated with a favorable response rate, including a 16% CR.