title: A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer: Southwest Oncology Group Study 0338.
abstract: BACKGROUND
  Imatinib mesylate is a potent inhibitor of the Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases. On the basis of variable expression of c-Kit and PDGFR in breast cancer and of in vitro data supporting synergy between imatinib and capecitabine, the Southwest Oncology Group conducted a phase II trial of the combination in metastatic breast cancer.
  
  
  METHODS
  Eligible patients had progressive, measurable metastatic breast cancer and received<or=2 previous chemotherapy regimens for metastatic disease. Previous 5-fluorouracil or capecitabine for metastatic disease was not allowed. Patients were accrued on a 2-stage design and received imatinib mesylate 400 mg by mouth daily and capecitabine at 1000 mg/m2 by mouth twice daily for 14 days of a 21-day cycle. The primary endpoint was the confirmed response rate (RR). Tumors were evaluated for c-Kit, PDGFR-beta, and hormone receptor expression.
  
  
  RESULTS
  Nineteen fully evaluable patients were enrolled, with a confirmed RR of 11% (95% CI, 1%-33%). Eleven percent had unconfirmed partial responses, and 42% had stable disease. The trial did not accrue to the second stage. The estimated 6-month progression-free survival was 16% (95% CI, 0%-32%), and the median overall survival was 14 months (95% CI, 7-15 months). The combination was well tolerated. Of 8 available tumor samples, 2 stained for c-Kit, and all had stromal staining for PDGFR-beta.
  
  
  CONCLUSIONS
  In unselected patients, the combination of imatinib mesylate and capecitabine was well tolerated but did not result in improved RRs compared to those reported with capecitabine alone.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA. helen.chew@ucdmc.ucdavis.edu
authors.forename: Helen K
authors.initials: HK
authors.lastname: Chew
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.forename: Kathy
authors.initials: K
authors.lastname: Albain
authors.forename: Danika
authors.initials: D
authors.lastname: Lew
authors.forename: Allen
authors.initials: A
authors.lastname: Gown
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Julie
authors.initials: J
authors.lastname: Gralow
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Robert
authors.initials: R
authors.lastname: Livingston
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011743:Pyrimidines / Q000008:administration & dosage*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003841:Deoxycytidine; D000069287:Capecitabine; D000068877:Imatinib Mesylate; C099852:PDGF receptor tyrosine kinase; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D005472:Fluorouracil