Investigational New Drugs

, Volume 25, Issue 3, pp 211–216

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

  • S. Kalmadi
  • M. Davis
  • A. Dowlati
  • S. O’Keefe
  • M. Cline-Burkhardt
  • R. J. Pelley
  • E. Borden
  • R. Dreicer
  • R. Bukowski
  • T. Mekhail
Phase I Studies

DOI: 10.1007/s10637-006-9025-4

Cite this article as:
Kalmadi, S., Davis, M., Dowlati, A. et al. Invest New Drugs (2007) 25: 211. doi:10.1007/s10637-006-9025-4

Summary

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.

Keywords

Lenalidomide Revlimid Phase I study Solid tumor Docetaxel Carboplatin 

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • S. Kalmadi
    • 1
  • M. Davis
    • 1
  • A. Dowlati
    • 1
  • S. O’Keefe
    • 1
  • M. Cline-Burkhardt
    • 1
  • R. J. Pelley
    • 1
  • E. Borden
    • 1
  • R. Dreicer
    • 1
  • R. Bukowski
    • 1
  • T. Mekhail
    • 1
  1. 1.Taussig Cancer CenterClevelandUSA

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