Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer.

ABSTRACT: This dose-finding study evaluated lenvatinib, an oral multitargeted receptor tyrosine kinase inhibitor, in combination with carboplatin/paclitaxel in chemotherapy-naïve non-small-cell lung cancer (NSCLC) patients.Patients received lenvatinib twice daily (BID) with carboplatin (area under the curve 6?mg?ml(-1)?min(-1), day 1)/paclitaxel (200?mg?m(-2), day 1) every 3 weeks. The initial dose of lenvatinib was 6?mg BID. The primary end point was maximum tolerated dose (MTD) of lenvatinib. At the MTD, the cohort was expanded by 16 patients. Safety, pharmacokinetics, pharmacodynamics, and antitumor effects were evaluated.Twenty-eight patients were treated. At 6?mg BID, dose-limiting toxicities (DLTs) included febrile neutropenia/gingival infection (n=2). No DLTs occurred with 4?mg BID, the recommended MTD for the expansion. Common grade 3/4 toxicities included neutropenia, leukopenia, hypertension, and thrombocytopenia. The combination had no significant impact on individual drug pharmacokinetics. Response rate and median progression-free survival were 68% and 9.0 months, respectively, with 4?mg BID. In the plasma biomarker analysis, stromal cell-derived factor 1?, stem cell factor, and granulocyte colony-stimulating factor correlated with antitumor activity.The MTD for lenvatinib with carboplatin/paclitaxel is 4?mg BID in advanced NSCLC patients. This regimen demonstrated manageable tolerability and encouraging antitumor activity.

SUBMITTER: Nishio M 

PROVIDER: S-EPMC3738144 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature