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

• Published in: Clinical breast cancer 2010-04, Vol.10 (2), p.148-153
• Main Authors: Pippen, John, Elias, Anthony D, Neubauer, Marcus, Stokoe, Christopher, Vaughn, LaTrice G, Wang, Yanping, Orlando, Mauro, Shonukan, Oluwatoyin, Muscato, Joseph, O'Shaughnessy, Joyce A, Gralow, Julie
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dexamethasone; ER-positive; Female; Glutamates - administration & dosage; Glutamates - adverse effects; Guanine - administration & dosage; Guanine - adverse effects; Guanine - analogs & derivatives; Hematology, Oncology and Palliative Medicine; HER-positive; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neutropenia; Obstetrics and Gynecology; Pemetrexed; Salvage Therapy - methods; Taxoids - therapeutic use; Treatment Outcome; Triple-negative; Vitamin B 12; Vitamin supplementation
• ISSN: 1526-8209; 1938-0666
• DOI: 10.3816/CBC.2010.n.020

Abstract Purpose This 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 Methods Eligible 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). Results Between 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%). Conclusion Pemetrexed/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.