title: Phase II trial of docetaxal plus imatinib mesylate in the treatment of patients with metastatic breast cancer.
abstract: BACKGROUND
  Inhibition of the platelet-derived growth factor receptor (PDGFR) might improve the efficacy of chemotherapy by lowering interstitial tumor pressure and allowing increased tumor penetration by cytotoxic agents. In this phase II trial, we added imatinib, a PDGFR inhibitor, to docetaxel in the first-line treatment of women with metastatic breast cancer (MBC).
  
  
  METHODS
  Women with MBC who had received a maximum of 1 previous chemotherapy regimen were eligible for this trial. Initially, patients received oral imatinib 600 mg daily and docetaxel 30 mg/m2 on days 1, 8, and 15 of a 28-day cycle. The imatinib dose was lowered from 600 mg to 400 mg daily because of toxicity (primarily gastrointestinal) observed in the first 15 patients. Patients were evaluated for response (Response Evaluation Criteria in Solid Tumors) after 8 weeks of therapy; treatment continued in responding/stable patients until tumor progression or unacceptable toxicity. The primary endpoint was the overall response rate.
  
  
  RESULTS
  Thirty-seven patients entered this trial between May 2005 and March 2008. This regimen was relatively poorly tolerated, even after reduction of the imatinib dose, primarily because of gastrointestinal toxicity (nausea, vomiting, and diarrhea). Eight patients (22%) stopped therapy because of toxicity before the 8-week initial evaluation. Six of 37 enrolled patients (16%; 95% CI, 4.3%-28.1%) had partial responses; an additional 4 patients had stable disease for > 6 months. The median progression-free and overall survivals were 9.3 months and 15.4 months, respectively.
  
  
  CONCLUSIONS
  When compared with previous results with single-agent docetaxel, the combination of weekly docetaxel plus imatinib was tolerated relatively poorly and produced a low objective response rate. The efficacy of weekly docetaxel is not improved by concurrent administration of imatinib as a PDGFR inhibitor.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Markus
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Mark
authors.initials: M
authors.lastname: Mainwaring
authors.forename: David M
authors.initials: DM
authors.lastname: Waterhouse
authors.forename: Charles D
authors.initials: CD
authors.lastname: Webb
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001549:Benzamides; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D000077143:Docetaxel; D000068877:Imatinib Mesylate