Moving Forward with Capecitabine: a Glimpse of the Future

Abstract Learning Objectives After completing this course, the reader will be able to: Appreciate the emerging role of capecitabine monotherapy in the treatment of advanced breast cancer. Explain the current status of capecitabine monotherapy as first or second line therapy in patients with advanced breast cancer. Describe the rationale and current status of capecitabine combination treatment of breast cancer. Balance the safety profile of capecitabine with available alternative treatment options for the treatment of advanced breast cancer. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Oral capecitabine is a useful chemotherapy for metastatic breast cancer, both as monotherapy and in combination with other cytotoxic drugs. The proven activity of capecitabine has provided the rationale to explore its use earlier in the course of the disease and in combination with other agents, particularly those known to further upregulate thymidine phosphorylase (TP) concentrations in tumor tissue. The efficacy and safety of capecitabine monotherapy compares favorably with cyclophosphamide/methotrexate/5-fluorouracil in chemotherapy-naïve patients and with paclitaxel in anthracycline-pretreated patients. Therefore, for patients whose disease has progressed during or following anthracycline treatment, but for whom capecitabine/docetaxel combination therapy or taxane monotherapy is not appropriate, capecitabine monotherapy is an attractive alternative to established i.v. treatments. In combination, capecitabine plus paclitaxel, which further upregulates TP in tumor tissue, has demonstrated high activity in two phase II studies in advanced/metastatic breast cancer. Similarly, combination with vinorelbine showed promising activity in pretreated metastatic breast cancer patients, and triple combinations with an anthracycline and a taxane or cyclophosphamide have proven to be highly active. In the future, capecitabine may be combined with novel biologic agents, such as trastuzumab and bevacizumab; the former combination has already shown encouraging results in a pilot trial. Confirmatory studies for many of these combinations and phase III trials versus standard therapy are now warranted.