title: Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles.
abstract: 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.
authors.affiliation: Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH 44106, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Sanborn
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Cooney
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Brell
authors.forename: Smitha
authors.initials: S
authors.lastname: Krishnamurthi
authors.forename: Joseph
authors.initials: J
authors.lastname: Gibbons
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bokar
authors.forename: Charles
authors.initials: C
authors.lastname: Nock
authors.forename: Anne
authors.initials: A
authors.lastname: Ness
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: 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
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D017239:Paclitaxel