Phase II study of UFT plus leucovorin in women 65 years and older with advanced breast cancer

The investigation of new treatment approaches for older women with advanced breast cancer remains a priority. The tolerability of treatment is a major consideration for this population. UFT offers a favorable side effect profile and may be administered orally with good bioavailability. The combination of UFT and leucovorin (Orzel®) has demonstrated activity in patients with MBC(Proc Am Soc Clin Oncol 2:47a, 2001). We undertook a phase II study to assess the efficacy and safety of Orzel® in pts 65 years and older with advanced breast cancer. The regimen included UFT 300 mg/m2/day orally as two divided doses and leucovorin 30 mg orally with each UFT dose for 21 consecutive days followed by a one week break (cycle duration = 28 days). Eligibility criteria included locally advanced or stage IV breast cancer with measurable disease, <2 prior chemotherapy regimens for MBC, CALGB performance status (PS) 0-2, and adequate hematologic, renal and hepatic function. To date, 8 women with a median age of 71 years and a median PS of 0 have enrolled. Three received prior chemotherapy for MBC. Nineteen cycles of therapy were administered (median number 2, range 1-5). Grade 3 non-hematologic toxicities included: diarrhea (3 pts), fatigue (3 pts), nausea (2 pts), vomiting (1 pt) and elevated prothrombin time (1 pt). Grade 4 non-hematologic toxicities included: diarrhea (1 pt) and elevated prothrombin time (1 pt). Grade 3 or 4 diarrhea resulted in 1 out of 4 pts who were 65-69 years of age and in 3 out of four pts greater than age 70 years. No significant hematologic toxicity was observed. Six pts have been evaluated for response: 3 stable disease and 3 progressive disease. Preliminary analysis of this trial indicates that diarrhea is the dose-limiting toxicity of Orzel® in pts over the age of 65 years where the incidence and severity of diarrhea appeared greatest in pts over 70 years. Based on this finding, the protocol has been amended to decrease the dose of UFT to 250 mg/m2/day for all patients 70 years and older. Since older persons have been under-represented in clinical trials,the tolerability of cancer chemotherapy has not been well studied in these individuals. As the segment of the population over age 70 increases, it is essential to ascertain the safety and efficacy of anticancer therapies in this group.