FDA has approved Xeloda, an oral treatment for advanced breast cancer patients, whose tumors are resistant to Taxol (paclitaxel) with an anthracycline, such as Adriamycin (doxorubicin), or in patients whose tumors are resistant to paclitaxel and further anthracycline therapy may be contraindicated. Xeloda has been granted accelerated approval — a regulatory mechanism that allows early approval of a product for the treatment of life-threatening conditions for which no acceptable alternative treatments exist or which provides a meaningful therapeutic benefit over existing treatments. Accelerated approval is based on a surrogate marker for clinical benefit such as measurable shrinkage of a tumor rather than a documented effect on the clinical benefit itself such as survival.
Xeloda’s approval was based on a phase II study showing that some patients demonstrated shrinkage of their tumor while taking the drug. In a subgroup of 43 patients resistant to both an anthracycline and Taxol, about a quarter had shrinkage of their tumor for a median duration of 154 days. In all 135 patients with measurable disease and who had been treated with one cancer drug, Taxol, tumors shrank by at least half in about 18.5 percent of patients. The most frequently reported side effects in the clinical trial included diarrhea, nausea, vomiting, a painful inflammation of the mouth, fatigue, hand-foot syndrome characterized by a painful rash and swelling of the hands or feet and mild bone marrow suppression. About one third of the patients have serious side effects, but these side effects were generally reversible after interruption of treatment or decreasing the dose.
A recent(2009) review idenitified 6 capecitabine and 2 vinorelbine phase III trials, numerous phase II monotherapy studies and 35 phase I/II studies exploring capecitabine–vinorelbine combination therapy (1 with trastuzumab in HER2-positive MBC).
Several guidelines state: “There is insufficient evidence for the use of capecitabine as a first-line chemotherapy in metastatic breast cancer.” This is the position as well of NICE as well as other guidelines. NCCN, on the other hand (p. 45) lists Xeloda without comment as an option for metastatic breast cancer.
There are several phase II studies that indicate that capecitabine and paclitaxel is a well tolerated and effective regimen. On the other hand, the comparative trial was presented at ASCO in 2007 and did not establish noninferiority against epirubicin and paclitaxel.
Breast Cancer Disease Site Group. Tomiak E, Verma S, Trudeau M, Robinson P. Capecitabine in stage IV breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 Nov 26 [online update]. 17 p. (Practice guideline report; no. 1-16). [31 references] http://www.cancercare.on.ca/pdf/pebc1-16f.pdf National Institute for Clinical Excellence (NICE). Guidance on the use of capecitabine for the treatment of locally advanced or metastatic breast cancer. London (UK): National Institute for Clinical Excellence (NICE); 2003 May. 24 p. (Technology appraisal; no. 62). Arlene Chan, Mark Verrill Capecitabine and vinorelbine in metastatic breast cancer European Journal of Cancer – September 2009 (Vol. 45, Issue 13, Pages 2253-2265
Frye DK.Capecitabine-based combination therapy for breast cancer: implications for nurses.Oncol Nurs Forum. 2009 Jan;36(1):105-13.
Barrett-Lee et al Contemporary Issues and the Potential Uses of Capecitabine (Xeloda) in Metastatic Breast Cancer Cancer Treatment Review Nov 2009 35(7):582-9