FDA Approves Capecitabine Plus Docetaxel for Metastatic Breast Cancer

November 1, 2001

The US Food and Drug Administration (FDA) recently approved the use of capecitabine (Xeloda) in combination with docetaxel (Taxotere) for the treatment of metastatic breast cancer in patients who failed anthracycline therapy.

The US Food and Drug Administration (FDA)recently approved the use of capecitabine (Xeloda) in combination with docetaxel(Taxotere) for the treatment of metastatic breast cancer in patients who failedanthracycline therapy. This regimen is the first chemotherapy combination tosignificantly extend survival (by 3 months) in these patients compared todocetaxel alone.

Previously, docetaxel monotherapy (100 mg/m² on day 1 of each21-day cycle) was the only regimen to demonstrate improved survival over thatachieved with the standard combination regimen of mitomycin (Mutamycin) andvinblastine. Recent findings indicate that patients treated with the combinationof capecitabine and docetaxel had a superior survival and a 22.5% reduced riskof mortality (hazard ratio: 0.775, P = .013) compared to those treated withdocetaxel alone. In addition, the combination produced significantly superiortumor response rates (32% vs 22% for docetaxel alone) and longer time to diseaseprogression (6.1 months vs 4.2 months).

"Xeloda combined with Taxotere is an important treatmentimprovement for women with metastatic breast cancer," said Joyce O’Shaughnessy,md, codirector of breast cancer research at Baylor-Sammons Cancer Center and USOncology. "The clinical data showed significant improvements in survival,tumor response, and time to disease progression for the combination compared toTaxotere alone in patients after failure of anthracycline treatment. Thisrepresents a major advance in the management of women with metastatic breastcancer, as improvements in survival are the bottom line."

Clinical Trial Results

The FDA decision was based on the results of a large phase IIItrial in 511 patients that compared capecitabine in combination with docetaxelto docetaxel alone and looked at survival, time to disease progression, andtumor response rate. Women with metastatic breast cancer who had failedtreatment with an anthracycline were randomized to either the combination(oral capecitabine, 1,250 mg/m² twice daily, days 1 to 14 with 1 week of rest,plus IV docetaxel, 75 mg/m², day 1 of each 21-day treatment cycle) ormonotherapy (IV docetaxel 100 mg/m², day 1 of each 21-day cycle).

The combination produced significantly better outcomes thandocetaxel alone. Median survival among women in the combination group comparedto the monotherapy group was 14.5 vs 11.5 months (P = .013), median time todisease progression was 6.1 vs 4.2 months (P = .001), and the tumorresponse rate was 32% vs 22% (P = .009). The trial was conducted in the UnitedStates, Canada, and Australia, as well as countries in Europe, Asia, and LatinAmerica.

Adverse events, including diarrhea, stomatitis, hand-footsyndrome, and nausea and vomiting, were observed more commonly in thecombination therapy group. These effects, however, proved to be manageable withappropriate medical intervention and dose interruptions. Dose reductionsdecreased the overall incidence of these events in subsequent cycles. Patientswho received docetaxel therapy alone experienced a higher incidence ofneutropenic fever, myalgia, and arthralgia.