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

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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.

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Acknowledgements

Supported by the National Cancer Institute Clinical Trials Evaluation Program Grant CA62502; Celgene Corporation, Warren, New Jersey; and Sanofi-Aventis Pharmaceuticals, Bridgewater, New Jersey.

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Authors and Affiliations

  1. Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH, 44106, USA

    Sharon L. Sanborn, Matthew M. Cooney, Afshin Dowlati, Joanna M. Brell, Smitha Krishnamurthi, Joseph Gibbons, Joseph A. Bokar, Charles Nock & Anne Ness

  2. Mary Babb Randolph Cancer Center, West Virginia University, 1801 Health Sciences South, P.O. Box 9300, Morgantown, WV, 26506, USA

    Scot C. Remick

Authors
  1. Sharon L. Sanborn
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  2. Matthew M. Cooney
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Correspondence to Matthew M. Cooney.

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Sanborn, S.L., Cooney, M.M., Dowlati, A. et al. Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles. Invest New Drugs 26, 355–362 (2008). https://doi.org/10.1007/s10637-008-9137-0

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  • DOI: https://doi.org/10.1007/s10637-008-9137-0

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