Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes.

Abstract

PURPOSE:

The oral fluoropyrimidine carbamate, capecitabine, is a highly active and well-tolerated treatment for metastatic breast cancer. In patients treated previously with anthracyclines and taxanes, capecitabine is an approved single-agent therapy. Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER-2), is also highly active in HER-2-overexpressing breast cancer. We have conducted a phase II study to confirm activity and feasibility of capecitabine and trastuzumab in combination in HER-2-overexpressing advanced/metastatic breast cancer.

PATIENTS AND METHODS:

Twenty-seven patients with HER-2-overexpressing metastatic breast cancer previously treated with anthracyclines and/or taxanes received oral capecitabine 1,250 mg/m(2) bid for 14 days followed by a 7-day rest period combined with intravenous trastuzumab 4 mg/kg body weight on day 1 (loading dose) followed by 2 mg/kg weekly.

RESULTS:

Capecitabine/trastuzumab treatment achieved objective responses in 12 patients (45%), including complete response in four patients (15%) and partial response in eight patients (30%). Disease was stabilized in an additional nine patients (33%). The median overall survival time was 28 months, and the median progression-free survival time was 6.7 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were pain, hand-foot syndrome, and GI toxicities. Severe myelosuppression was rare and severe alopecia did not occur.

CONCLUSION:

These data confirm that the combination of capecitabine and trastuzumab is highly active in patients with HER-2-overexpressing anthracycline- and/or taxane-pretreated breast cancer, with only slight restrictions regarding quality of life.

• Authors: Gerhard Schaller, Ilka Fuchs, Thomas Gonsch, Jan Weber, Anke Kleine-Tebbe, Peter Klare, Hans-Joachim Hindenburg, Volker Lakner, Axel Hinke, Nikola Bangemann
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 22 Pg. 3246-50 (Aug 1 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17577021 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antimetabolites, Antineoplastic
• Taxoids
• Deoxycytidine
• Capecitabine
• Receptor, Epidermal Growth Factor
• Receptor, ErbB-2
• Trastuzumab
• Fluorouracil

Topics

• Adult
• Aged
• Anthracyclines (administration & dosage)
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antimetabolites, Antineoplastic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease Progression
• Fluorouracil (administration & dosage, analogs & derivatives)
• Germany
• Humans
• Middle Aged
• Receptor, Epidermal Growth Factor (antagonists & inhibitors)
• Receptor, ErbB-2 (analysis)
• Survival Rate
• Taxoids (administration & dosage)
• Trastuzumab
• Treatment Outcome