Investigational New Drugs

, 26:355 | Cite as

Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles

  • Sharon L. Sanborn
  • Matthew M. Cooney
  • Afshin Dowlati
  • Joanna M. Brell
  • Smitha Krishnamurthi
  • Joseph Gibbons
  • Joseph A. Bokar
  • Charles Nock
  • Anne Ness
  • Scot C. Remick
PHASE I STUDIES

Summary

Purpose: Pre-clinical models have demonstrated the benefit of metronomic schedules of cytotoxic chemotherapy combined with anti-angiogenic compounds. This trial was undertaken to determine the toxicity of a low dose regimen using docetaxel and thalidomide. Patients and Methods: Patients with advanced solid tumors were enrolled. Thalidomide 100mg twice daily was given with escalating doses of docetaxel from 10 to 30mg/m2/week. One cycle consisted of 12 consecutive weeks of therapy. The maximal tolerated dose (MTD) was defined as the dose of thalidomide along with docetaxel that caused ≤grade 1 non-hematologic or ≤grade 2 hematologic toxicity for cycle one. Results: Twenty-six patients were enrolled. Dose-limiting toxicities (DLTs) were bradycardia, fatigue, fever, hyperbilirubinemia, leukopenia, myocardial infarction, and neutropenia. Prolonged freedom from disease progression was observed in 44.4% of the evaluable patients. Conclusions: This anti-angiogenic regimen was well tolerated and demonstrated clinical benefit. The recommended phase II dosing schedule is thalidomide 100mg twice daily with docetaxel 25mg/m2/week.

Keywords

Metronomic Docetaxel Thalidomide Angiogenesis Phase I 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Sharon L. Sanborn
    • 1
  • Matthew M. Cooney
    • 1
  • Afshin Dowlati
    • 1
  • Joanna M. Brell
    • 1
  • Smitha Krishnamurthi
    • 1
  • Joseph Gibbons
    • 1
  • Joseph A. Bokar
    • 1
  • Charles Nock
    • 1
  • Anne Ness
    • 1
  • Scot C. Remick
    • 2
  1. 1.Division of Hematology and OncologyUniversity Hospitals Case Medical Center, Case Comprehensive Cancer CenterClevelandUSA
  2. 2.Mary Babb Randolph Cancer CenterWest Virginia UniversityMorgantownUSA

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