A phase II study of a combination of pemetrexed (Pem) and gemcitabine (Gem) in patients with metastatic breast cancer (MBC): An NCCTG study

Abstract

639 Background: Pem inhibits folate-dependent enzymes involved in thymidine and purine synthesis, has broad clinical activity, and exhibits synergistic cytotoxicity with Gem in preclinical models. We conducted a phase II study to assess the efficacy and toxicity of this combination in MBC. Methods: Eligible patients (pts) must have had an anthracycline and a taxane in either adjuvant or metastatic setting with no more than 1 chemotherapy regimen for metastatic disease (unless a taxane and anthracycline). Pts received Gem 1250 mg/m2 (IV; d1, 8) and P 500 mg/m2 (IV; d8) q21 days. Results: Fifty-nine pts were enrolled with median age of 51 (range 32–74), prior adjuvant chemotherapy regimens 0 (5 pts, 8%) or 1 (54 pts, 92%), prior metastatic chemotherapy regimens 0 (23 pts, 39%), 1 (35 pts, 59%), or 2 (1 pt, 2%). Twenty-eight (48%) had received prior hormonal therapy. Pts received treatments for a median of 5 cycles (range: 1–21) with median follow-up of 426 days. Considering grade 3 and 4 toxicities, 48 (81%) pts had neutropenia (gr 3: 11, gr 4: 37), but only 7 (12%) had febrile neutropenia. Fifteen pts (25%) had thrombocytopenia (gr 3: 13, gr 4: 2). Grade 3+ non-hematologic toxicity included 10 (17%) pts with dyspnea, 10 (17%) with fatigue, 4 (7%) with rash, 3 (5%) with nausea, and 3 (5%) with anorexia. Overall, 14 (24%; 95% CI: 16–39%) pts achieved PR with a median duration of at least 5 months. Nine (15%) had SD for ≥ 6 months with a median of 334 days (range 205–786). Median time to progression was 3.8 months (95% CI 2.6–5.7). Median survival was 10.3 months (95% CI 8.4–26.4) and the 1-year survival rate was 49% (95% CI 37–64%). Conclusions: The combination of Pem and Gem has activity and produces clinical benefit (CR + PR + SD ≥ 6 months) in 39% of pts with MBC who have previously been treated with an anthracycline and a taxane. No significant financial relationships to disclose.