MEXICO CITY-In patients with metastatic breast cancer, capecitabine (Xeloda) monotherapy followed by taxane monotherapy offers greater benefits in social functioning than capecitabine/ taxane concurrent therapy. In some patients, sequential therapy with capecitabine administered before taxanes may therefore be a more appropriate treatment strategy than capecitabine/docetaxel (Taxotere) or capecitabine/paclitaxel combination therapy after anthracycline failure. These early results from a quality of life (QOL) study conducted by the Mexican Oncology Study Group were reported by Laura Torrecillas, MD, medical oncologist and head of the chemotherapy service at the 20 Noviembre ISSSTE Medical Center in Mexico (ASCO abstract 3011). At the interim analysis, the phase III ongoing trial shows a similar disease control rate and a slightly inferior toxicity profile with capecitabine alone followed by taxane, compared with the combination of capecitabine and docetaxel or paclitaxel. This study looked at whether sequential monotherapy could improve QOL more than a first-line combined approach. Preliminary Data Focus on Capecitabine Monotherapy "In these preliminary data, few of the patients in the sequential arm have received taxane therapy, and therefore the results are more representative of capecitabine monotherapy than sequential capecitabine monotherapy followed at progression by taxane monotherapy. However, mature results will provide a clearer indication of any differences between these two treatment strategies" Dr. Torrecillas noted. In describing the rationale for the phase III study, the investigators pointed out that capecitabine monotherapy has demonstrated consistently high efficacy and a favorable safety profile in patients with metastatic breast cancer who have been pretreated either with anthracyclines or with a combination of anthracyclines and taxanes. Capecitabine is an oral, fluoropyrimidine carbamate that generates fluorouracil (5-FU) preferentially in tumor tissue through exploitation of high intratumoral concentrations of thymidine phosphorylase (TP). The oral administration and good tolerability of capecitabine offer improved patient convenience, which would potentially enhance patient QOL. From one perspective, the high single-agent activity of capecitabine, and the lack of overlapping toxicity profiles with taxanes, in addition to their synergistic activity due to TP upregulation in tumor tissue, suggest that they are most effectively administered in combination. However, sequential therapy with capecitabine administered as monotherapy followed by taxanes at disease progression has the potential to provide additional QOL benefits compared with combination therapy from the outset, assuming that efficacy for cancer control is satisfactory. Three Treatment Arms The study compared three treatment arms:

• capecitabine monotherapy 1,250 mg/m² twice daily, days 1 to 14, followed by docetaxel or paclitaxel after progression (58 patients) vs
• capecitabine/paclitaxel combination therapy, with capecitabine 825 mg/m² twice daily, days 1 to 14, plus paclitaxel 175 mg/m² day 1 (66 patients) vs
• capecitabine/docetaxel combination therapy, with capecitabine 825 mg/m² twice daily, days 1 to 14 plus docetaxel 75 mg/m² day 1 (69 patients).

The treatment is continued until disease progression or unacceptable toxicity. Side effects are managed by treatment interruption or dose reduction. The investigators report that the baseline characteristics were generally well balanced in the three groups. To be eligible for the study, patients were required to have measurable metastatic breast cancer, be between 18 and 75 years old, have a Karnofsky performance status ≥ 50, have a life expectancy greater than 3 months, and one prior anthracycline-based chemotherapy regimen. Prior adjuvant therapy with cyclophosphamide, methotrexate, fluorouracil (CMF) was also permitted. Patients could not have had hormonal therapy less than 30 days prior to enrollment. Questionnaire Assesses Trends QOL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 v2.0. The questionnaire is completed at baseline and at 3- week intervals (always before each treatment cycle) until week 48, and at the end of the study. More than 80% of patients completed at least one QOL questionnaire after the start of the study and were therefore evaluable for the QOL outcome. Substantially more questionnaires were completed at the end of the study in the capecitabine/ docetaxel arm compared with the other two study arms. The global health status was similar in all three treatment arms. "No consistent or sustained trends have been observed in global health status during the study period," Dr. Torrecillas reported. "At cycle eight, global health status is significantly improved with capecitabine/paclitaxel compared with the other two arms, but there are no significant differences between treatment arms at the end of the study." Social functioning was significantly improved with capecitabine monotherapy followed by taxane monotherapy compared with the other two study arms. "This is possibly due to the oral administration route and favorable tolerability (including lack of hair loss) associated with taxane monotherapy," Dr. Torrecillas explained. "Further data are required to improve the robustness of the results," Dr. Torrecillas noted. "In addition, inclusion of data after administration of taxane therapy in the sequential arm will provide a more accurate representation of sequential therapy rather than the currently available data for the single-agent capecitabine."