A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer: Southwest oncology group study 0338

Helen Chew, William Barlow, Kathy Albain, Danika Lew, Allen Gown, Daniel Hayes, Julie Gralow, Gabriel Hortobagyi, Robert B Livingston

Research output: Contribution to journalArticle

26 Citations (Scopus)

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. Patients and Methods: Eligible patients had progressive, measurable metastatic breast cancer and received - 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-β, 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-β. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
JournalClinical Breast Cancer
Volume8
Issue number6
DOIs
StatePublished - Dec 1 2008

Fingerprint

Platelet-Derived Growth Factor Receptors
Breast Neoplasms
Mouth
Fluorouracil
Growth Hormone
Disease-Free Survival
Neoplasms
Capecitabine
Imatinib Mesylate
Staining and Labeling
Drug Therapy
Survival

Keywords

  • C-Kit
  • Platelet-derived growth factor
  • Targeted therapy receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer : Southwest oncology group study 0338. / Chew, Helen; Barlow, William; Albain, Kathy; Lew, Danika; Gown, Allen; Hayes, Daniel; Gralow, Julie; Hortobagyi, Gabriel; Livingston, Robert B.

In: Clinical Breast Cancer, Vol. 8, No. 6, 01.12.2008, p. 511-515.

Research output: Contribution to journalArticle

Chew, Helen ; Barlow, William ; Albain, Kathy ; Lew, Danika ; Gown, Allen ; Hayes, Daniel ; Gralow, Julie ; Hortobagyi, Gabriel ; Livingston, Robert B. / A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer : Southwest oncology group study 0338. In: Clinical Breast Cancer. 2008 ; Vol. 8, No. 6. pp. 511-515.
@article{cb3c602833684b83b682ecb1bc18c907,
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. Patients and Methods: Eligible patients had progressive, measurable metastatic breast cancer and received - 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-β, 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-β. Conclusion: 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.",
keywords = "C-Kit, Platelet-derived growth factor, Targeted therapy receptor",
author = "Helen Chew and William Barlow and Kathy Albain and Danika Lew and Allen Gown and Daniel Hayes and Julie Gralow and Gabriel Hortobagyi and Livingston, {Robert B}",
year = "2008",
month = "12",
day = "1",
doi = "10.3816/CBC.2008.n.062",
language = "English (US)",
volume = "8",
pages = "511--515",
journal = "Clinical Breast Cancer",
issn = "1526-8209",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer

T2 - Southwest oncology group study 0338

AU - Chew, Helen

AU - Barlow, William

AU - Albain, Kathy

AU - Lew, Danika

AU - Gown, Allen

AU - Hayes, Daniel

AU - Gralow, Julie

AU - Hortobagyi, Gabriel

AU - Livingston, Robert B

PY - 2008/12/1

Y1 - 2008/12/1

N2 - 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. Patients and Methods: Eligible patients had progressive, measurable metastatic breast cancer and received - 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-β, 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-β. Conclusion: 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.

AB - 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. Patients and Methods: Eligible patients had progressive, measurable metastatic breast cancer and received - 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-β, 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-β. Conclusion: 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.

KW - C-Kit

KW - Platelet-derived growth factor

KW - Targeted therapy receptor

UR - http://www.scopus.com/inward/record.url?scp=60549115127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60549115127&partnerID=8YFLogxK

U2 - 10.3816/CBC.2008.n.062

DO - 10.3816/CBC.2008.n.062

M3 - Article

C2 - 19073506

AN - SCOPUS:60549115127

VL - 8

SP - 511

EP - 515

JO - Clinical Breast Cancer

JF - Clinical Breast Cancer

SN - 1526-8209

IS - 6

ER -