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


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.
Sanborn
Sharon L
SL
Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH 44106, USA.
Cooney
Matthew M
MM
Dowlati
Afshin
A
Brell
Joanna M
JM
Krishnamurthi
Smitha
S
Gibbons
Joseph
J
Bokar
Joseph A
JA
Nock
Charles
C
Ness
Anne
A
Remick
Scot C
SC
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D017239:Paclitaxel / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage
D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D017239:Paclitaxel