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01-08-2008 | PHASE I STUDIES

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

Authors: 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

Published in: Investigational New Drugs | Issue 4/2008

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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Title: Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles
Authors: 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
Publication date: 01-08-2008
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2008
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-008-9137-0

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