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 30 mg/m(2)/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 < or =grade 1 non-hematologic or < 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 100 mg twice daily with docetaxel 25 mg/m(2)/week.
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 30 mg/m(2)/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 < or =grade 1 non-hematologic or < 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 100 mg twice daily with docetaxel 25 mg/m(2)/week.
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: Elizabeth Horstmann; Mary S McCabe; Louise Grochow; Seiichiro Yamamoto; Larry Rubinstein; Troy Budd; Dale Shoemaker; Ezekiel J Emanuel; Christine Grady Journal: N Engl J Med Date: 2005-03-03 Impact factor: 91.245
Authors: Erin R Gardner; Martha Kelly; Eric Springman; Kyoung-jin Lee; Haiqing Li; William Moore; William D Figg Journal: Invest New Drugs Date: 2010-09-07 Impact factor: 3.850
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