MILAN, Italy-A reduced dose of oral capecitabine(Drug information on capecitabine) (Xeloda) is a welltolerated, effective, and convenient treatment for elderly patients with advanced breast cancer. These results of an Italian study were reported by one of the investigators, Laura Catena, MD, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy (ASCO abstract 3050). "There is a need for a well-tolerated and effective treatment in elderly breast cancer patients. Half of all breast cancers are in elderly women, and many treatments for advanced breast cancer are poorly tolerated by elderly patients," Dr. Catena explained. "Oral capecitabine enables convenient, outpatient treatment. It achieves consistently high efficacy in metastatic breast cancer, with a favorable safety profile characterized by a particularly low incidence of grade 3/4 adverse events, myelosuppression, and alopecia." Capecitabine, a tumor-activated, oral fluoropyrimidine, generates fluorouracil(Drug information on fluorouracil) (5-FU) preferentially in tumor tissue, and presents good activity in a wide range of solid tumors. 25% Dose Modification The open-label, noncomparative, phase II study was conducted at a single center between May 1999 and February 2003. The study evaluated the global therapeutic index of twice-daily oral capecitabine in elderly patients with locally advanced metastatic breast cancer. Patients received oral capecitabine 1,250 mg/m2 bid, days 1 to 14 every 21 days (n = 30). To improve the safety profile, the protocol was amended to a reduced dosage of oral capecitabine 1,000 mg/m2 bid, days 1 to 14 every 21 days (n = 43). This reduction was in response to new dosing guidelines recommending a 25% dose reduction in elderly, frail patients who may be at risk of an increased incidence of grade 3/4 toxicities. Patients with a partial response or stable disease had up to six cycles of treatment; patients with complete response had an additional two cycles, and patients with progressive disease were withdrawn from the study. A total of 73 patients were enrolled, and the median age of the patients was 72.9 years (range 65 to 89). All patients had measurable or evaluable advanced disease, Karnofsky performance status ≤ 2, and adequate bone marrow, cardiac, renal, and hepatic function. Patients could have had no more than one prior chemotherapy regimen and/or two hormonal regimens for metastatic disease. A previous therapy containing fluorouracil was allowed but a minimum period of 12 months was required starting from the last dosage of the previous treatment. The metastatic sites were soft tissue (28), bone (27), liver (26), lung (20), and others (20). The primary end points were the safety profile and tolerability, the secondary end points were response rate and time to progression. Most Completed Full Course Overall, 39 patients (53%) completed the full course of treatment. There was a similar incidence of premature withdrawal at the two treatment doses, and treatment- related adverse events led to premature withdrawal of 13 patients (18%). All patients were evaluable for toxicity and 62 patients for response. Toxicity according to National Cancer Institute- Common Toxicity Criteria (NCI-CTC) Bethesda guidelines was: grade 3/4 diarrhea (6%), grade 3 vomiting (7%), grade 1/2 hand-foot syndrome (47% in the higher-dose group and 30% in the lowdose group), grade 2/3 asthenia (26%), grade 2 stomatitis (11%). There were two deaths during the study; one due to treatment related diarrhea/dehydration, and one due to disease progression. "There were fewer dose reductions for adverse events required in patients receiving the lower dose compared with patients receiving the higher dose," noted the study's lead investigator, Giuseppe Procopio, MD, of Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. Considerable Activity "Oral capecitabine demonstrated considerable activity, achieving a high rate of disease control, with no significant differences between the lower and higher dose groups," Dr. Procopio continued. Disease control was 86% with the lower dose and 77% with the higher dose (see Table 1). Objective responses were documented in 36% of patients (26), with 3% complete remission, 32% with stabilization of disease, and 18% with progression. The median time to disease progression was 77 days (range 14-139 days). Dr. Catena reported that the study found a favorable safety profile of oral capecitabine 1,000 mg/m2 twice daily in elderly patients compared to the higher dose. "There was a low incidence of grade 3/4 adverse events and no grade 3/4 myelosuppression. There was a lower incidence of grade 3/4 diarrhea (2% vs 13%) and fewer dose reductions (2% vs 30%) compared with oral capecitabine 1,250 mg/m2 twice daily." This lower dose regimen is as effective and better tolerated than the higher dose regimen and can be recommended for elderly patients with locally advanced metastatic breast cancer," Dr. Catena concluded.