Phase I trial of three-weekly Docetaxel, Carboplatin and oral lenalidomide (Revlimid®) in patients with advanced solid tumors
Introduction: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy. Patients and methods: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, ≤2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as ≥ grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. Results: Three of four patients treated at dose level 1, docetaxel 60 mg/m2 and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1–14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level −1, docetaxel 60 mg/m2 and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1–14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer. Conclusions: Docetaxel 60 mg/m2 and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1–14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.