Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer.

ABSTRACT: Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells in a xenograft model. We conducted a Phase I study of lenalidomide and sorafenib in patients with advanced cancer.During the escalation phase, lenalidomide (days 1-21) and sorafenib (days 1-28) were given orally once daily at the following respective doses: level 1 (10 mg, 200 mg); level 2 (10 mg, 400 mg); level 3 (20 mg, 400 mg); and level 4 (25 mg, 400 mg) (1 cycle?=?28 days). A "3?+?3" study design was used.Forty-one patients were treated (median age: 50 years). The most common diagnoses were adenoid cystic carcinoma (N?=?9), ovarian adenocarcinoma (N?=?7), and melanoma (N?=?6); 142 cycles (median: 3) were administered. No dose-limiting toxicities were noted. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3-4 treatment-related toxicities were neutropenia, thrombocytopenia, skin rash, and thromboembolism. Of 38 patients who were evaluable for response, stable disease (SD) was noted in 53 % of patients (SD ?6 months: 16 %). Tumor types with SD ??6 months were as follows: ocular melanoma, 2/2 (100 %); other melanoma, 1/4 (25 %); adenoid cystic carcinoma, 2/9 (22 %); and ovarian cancer, 1/6 (17 %). The median progression-free survival duration was 3.5 months (95 % CI, 1.9-5.0), and the median overall survival duration was 12.3 months (95 % CI, 10.1-14.5).Lenalidomide and sorafenib was well tolerated and associated with disease stabilization for ?6 months in patients with melanoma, adenoid cystic carcinoma, and ovarian adenocarcinoma.

SUBMITTER: Ganesan P 

PROVIDER: S-EPMC5730367 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature