Use of capecitabine in stage IV breast cancer: An evidence summary

Topic. What is the role of capecitabine in the treatment of stage IV (metastatic) breast cancer? Perspective. Evidence was selected and reviewed by two members of the Cancer Care Ontario Practice Guidelines Initiative's Breast Cancer Disease Site Group (DSG). A draft of this evidence summary was reviewed and discussed by the Breast Cancer DSG, which comprises surgeons, medical oncologists, radiation oncologists, epidemiologists, a pathologist, a medical sociologist, and community representatives. Methodology. Sources of Evidence: Relevant evidence was identified by a systematic search of the MEDLINE, CANCERLIT, and the Cochrane Library databases, as well as conference proceedings and reference lists. Unpublished evidence was obtained from the United States Food and Drug Administration Web site, and from Hoffmann-La Roche Limited. Patient Population: Women with stage IV (metastatic) breast cancer. Outcomes of Interest: Time-to-tumour-progression, tumour response rate, and quality of life were the primary outcomes of interest. Also considered were survival and response duration. Results. Search Results: Two randomised controlled trials evaluating capecitabine in women with metastatic breast cancer were identified. One trial compared capecitabine with intravenous cyclophosphamide/methotrexate/fluorouracil (CMF) in patients receiving first-line chemotherapy for metastatic breast cancer. A second randomised controlled trial compared capecitabine with paclitaxel following anthracycline failure. Both studies were reported in abstract form. One multicentre uncontrolled trial evaluated the efficacy of capecitabine in heavily pretreated patients with paclitaxel-refractory metastatic breast cancer. Evidence on adverse effects came from an overview of toxicity data from three phase II studies in breast cancer and three phase II/III studies in colorectal cancer. Benefits: The uncontrolled trial in patients with paclitaxel-refractory metastatic breast cancer found the following: response rate was 20% (95% confidence interval [CI]: 14-28%), median time-to-progression was 3.2 months, and median survival was 12.8 months. Preliminary results from two randomised controlled trials failed to demonstrate any significant difference in response rate or time-to-progression when capecitabine was compared with paclitaxel as second- or third-line treatment or when it was compared with CMF as first-line treatment. Harms: The most common grade 3 or 4 adverse effects observed with capecitabine were: hand-foot syndrome (13%), diarrhoea (12%), stomatitis (4%), nausea (4%), and neutropenia (4%). Conclusions. The phase II trial in patients with paclitaxel-refractory metastatic breast cancer shows a promising response rate in heavily pretreated patients. Associated time-to-progression, survival, and improvement in clinical benefit response make capecitabine a reasonable treatment alternative in this difficult-to-treat patient subgroup if third- or fourth-line therapy is to be considered. Preliminary results from the two randomised controlled trials suggest that capecitabine needs to be further evaluated as an alternative to paclitaxel in patients whose tumour has progressed on an anthracycline-based regimen, and in selected women, as first-line therapy as an alternative to more toxic standard combination chemotherapy regimens. These results, however, should be confirmed by independent trials. Available data are limited and do not allow a firm clinical recommendation to be made for capecitabine's use in these two settings.