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, < 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. RESULTS: 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. CONCLUSIONS: 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.
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, < 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: L G Corral; P A Haslett; G W Muller; R Chen; L M Wong; C J Ocampo; R T Patterson; D I Stirling; G Kaplan Journal: J Immunol Date: 1999-07-01 Impact factor: 5.422
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: S Vincent Rajkumar; Suzanne R Hayman; Martha Q Lacy; Angela Dispenzieri; Susan M Geyer; Brian Kabat; Steven R Zeldenrust; Shaji Kumar; Philip R Greipp; Rafael Fonseca; John A Lust; Stephen J Russell; Robert A Kyle; Thomas E Witzig; Morie A Gertz Journal: Blood Date: 2005-08-23 Impact factor: 22.113
Authors: Nicholas Mitsiades; Constantine S Mitsiades; Vassiliki Poulaki; Dharminder Chauhan; Paul G Richardson; Teru Hideshima; Nikhil C Munshi; Steven P Treon; Kenneth C Anderson Journal: Blood Date: 2002-06-15 Impact factor: 22.113
Authors: C P Belani; A Einzig; P Bonomi; T Dobbs; M J Capozzoli; R Earhart; L J Cohen; J D Luketich Journal: Ann Oncol Date: 2000-06 Impact factor: 32.976
Authors: Toni K Choueiri; Robert Dreicer; Brian I Rini; Paul Elson; Jorge A Garcia; Snehal G Thakkar; Rachid C Baz; Tarek M Mekhail; Holly A Jinks; Ronald M Bukowski Journal: Cancer Date: 2006-12-01 Impact factor: 6.860
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Sharon L Sanborn; Joseph Gibbons; Smitha Krishnamurthi; Joanna M Brell; Afshin Dowlati; Joseph A Bokar; Charles Nock; Nancy Horvath; Jacob Bako; Scot C Remick; Matthew M Cooney Journal: Invest New Drugs Date: 2008-11-15 Impact factor: 3.850
Authors: Karam Kim; Sungkwan An; Hwa Jun Cha; Yeong Min Choi; Sung Jin Choi; In-Sook An; Hong Ghi Lee; Yoo Hong Min; Su-Jae Lee; Seunghee Bae Journal: Oncol Lett Date: 2012-11-30 Impact factor: 2.967