A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer: Southwest Oncology Group Study 0338.
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.
Chew
Helen K
HK
Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA. helen.chew@ucdmc.ucdavis.edu
Barlow
William E
WE
Albain
Kathy
K
Lew
Danika
D
Gown
Allen
A
Hayes
Daniel F
DF
Gralow
Julie
J
Hortobagyi
Gabriel N
GN
Livingston
Robert
R
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*
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