A Phase II Trial of Pemetrexed and Gemcitabine in Patients With Metastatic Breast Cancer Who Have Received Prior Taxane Therapy

PurposeThis phase II trial assessed efficacy and safety of pemetrexed plus gemcitabine to treat metastatic or locally advanced breast cancer in patients previously treated with taxanes.Patients and MethodsEligible women with advanced breast cancer treated with taxanes in the adjuvant or metastatic setting received pemetrexed 500 mg/m2 on day 1 followed by gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Hematologic toxicities limiting day 8 gemcitabine dosing were observed in the first 20 patients, prompting a protocol amendment to evaluate pemetrexed 500 mg/m2 followed by gemcitabine 1500 mg/m2 on day 1 of a 14-day cycle. Patients received folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate (ORR).ResultsBetween July 2003 and September 2006, 73 evaluable women (median age, 52.1 years; range, 28–73 years) were enrolled (21-day schedule: 21 patients, 52% estrogen receptor—positive, 24% HER2-positive; 14-day schedule: 52 patients, 58% ER-positive, 15% HER2-positive). For patients on the 21-day and 14-day schedules, median number of cycles was 4 (range, 1–8 cycles) and 5 (range, 1–38 cycles), respectively. The ORRs were 23.8% and 19.2%, respectively; median survival times were 16.2 months and 13.4 months. The most common grade 3/4 hematologic toxicities were neutropenia (71% vs. 33%) and leukopenia (24% vs. 14%); febrile neutropenia occurred in 10% and 6%. The most common grade 3/4 nonhematologic toxicity was fatigue (29% vs. 10%).ConclusionPemetrexed/gemcitabine given on a 21-day or 14-day schedule is active in patients with advanced breast cancer previously treated with taxanes. A 14-day schedule appears to result in fewer serious toxicities.