Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors

• Published in: Investigational new drugs 2007-06, Vol.25 (3), p.211-216
• Main Authors: Kalmadi, S, Davis, M, Dowlati, A, O'Keefe, S, Cline-Burkhardt, M, Pelley, R J, Borden, E, Dreicer, R, Bukowski, R, Mekhail, T
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Chemotherapy; Clinical outcomes; Clinical trials; Design standards; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Drug therapy; Female; Growth factors; Hematology; Humans; Immunomodulation; Immunotherapy; Infusions, Intravenous; Lenalidomide; Lung cancer; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms - drug therapy; Neoplasms - pathology; Neutropenia; Non-small cell lung carcinoma; Patients; Pharmacology; Prescription drugs; Side effects; Small cell lung carcinoma; Solid tumors; Targeted cancer therapy; Taxoids - administration & dosage; Thalidomide; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Toxicity; Treatment Outcome; Tumors
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-006-9025-4

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. 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, < or =2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as > or = grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. Three of four patients treated at dose level 1, docetaxel 60 mg/m(2) 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/m(2) 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. Docetaxel 60 mg/m(2) 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.