The Role of Capecitabine , an Oral , Enzymatically Activated Fluoropyrimidine , in the Treatment of Metastatic Breast Cancer

Capecitabine is an oral fluoropyrimidine that mimics continuous infusion 5-fluorouracil and generates 5-fluorouracil preferentially at the tumor site. It is activated via a three-step enzymatic pathway, the final step of which requires thymidine phosphorylase, an enzyme that is significantly more active in tumor than normal tissue. As an oral agent, capecitabine is more convenient for patients and medical personnel, and avoids the complications associated with venous access. This paper reviews the development and clinical experience of capecitabine in breast cancer treatment. Clinical trials have established the efficacy and tolerability of capecitabine in anthracyclineand taxane-pretreated metastatic breast cancer, showing that capecitabine is an effective therapy for patients who have exhausted all established treatment options. Moreover, randomized, phase II studies have demonstrated that capecitabine is effective in anthracycline-pretreated patients and as first-line therapy for metastatic breast cancer. In addition to its confirmed efficacy, the favorable safety profile of capecitabine, particularly the low myelosuppression rate, makes it an attractive agent for incorporation into combination regimens. Therefore numerous trials have assessed the feasibility of capecitabine-containing regimens, and have shown promising results. Capecitabine is an important new treatment option for breast cancer patients, and ongoing clinical trials should further define its role in a range of settings. The Oncologist 2001;6:56-64 The Oncologist 2001;6:56-64 www.TheOncologist. com Correspondence: Joanne L. Blum, M.D., Ph.D., U.S. Oncology, 3535 Worth Street, Suite 600, Dallas, Texas 75246, USA. Telephone: 214-370-1000; Fax: 214-370-1060; e-mail: Joanne.Blum@usoncology.com Received October 2, 2000; accepted for publication November 1, 2000; ©AlphaMed Press 1083-7159/2001/$5.00/0 INTRODUCTION Breast cancer represents a major cause of morbidity and mortality for women in the Western world, with 175,000 new cases occurring in the U.S. every year. Approximately 50% of all patients treated with curative intent will develop metastatic disease, and the median survival time for patients after diagnosis of metastatic disease is 18-30 months. The treatment of patients who are resistant to hormonal therapy, are hormone-receptor negative, or have rapidly progressive visceral disease usually involves systemic cytotoxic chemotherapy. Primary goals of treatment in this setting are the relief of tumor-related symptoms, maintenance of quality of life, control of disease progression and, ultimately, prolonged survival with acceptable toxicity. There is a need for convenient, well-tolerated, and effective agents for the treatment of patients with heavily pretreated metastatic breast cancer. The trend towards more aggressive treatment earlier in the disease course with agents such as paclitaxel or docetaxel, and the use of highly active agents in the adjuvant setting, have led to an increase in the number of patients presenting with metastatic disease that is resistant to or had failed taxanes and anthracyclines. Therefore, new therapeutic strategies are needed for these patients. Capecitabine, a novel oral fluoropyrimidine, mimics continuous infusion 5-fluorouracil (5-FU) and generates 5-FU preferentially at the tumor site through exploitation of high intratumoral thymidine phosphorylase (TP) concentrations. Capecitabine has become an important treatment option for patients with metastatic breast cancer that has progressed following taxane therapy, and has shown promise in anthracycline-pretreated patients, as first-line monotherapy, and as a component of combination regimens. This paper presents an overview of the development and clinical experience of capecitabine in the treatment of metastatic breast cancer. by gest on Sptem er 6, 2017 http://thologist.alpham edpss.org/ D ow nladed from