5,10 methylenetetrahydrofolic acid with fluorouracil as treatment for advanced breast cancer in patients who failed prior treatment with anthracyclines and taxanes: A phase II study

1136 Background: Fluorouracil (FU) has response rate activity in metastatic breast cancer in the range of 17–23%. Although leucovorin (LV) modestly enhances FU activity, it has not been typically combined with FU in this setting. While LV must undergo metabolic activation, 5,10 methylenetetrahydrofolic acid (CoFactor, CF) directly modulates FU inhibition of thymidylate synthase without the need for metabolic conversion. CF + FU demonstrated enhanced efficacy and reduced hematologic toxicity compared to LV + FU in rodent models. We evaluated CF + FU in advanced metastatic breast cancer (mBC) patients. Methods: Patients had HER2/neu-negative taxane and anthracycline refractory mBC, fewer than 3 prior therapies for advanced disease, and performance status ECOG 0–2. Prior FU or capecitabine-based palliative chemotherapy was not allowed. Thirty-two patients were enrolled, and 31 received at least one dose of drug. A treatment cycle was 60 mg/m2 CF and 500 mg/m2 FU, weekly IV bolus for 6 weeks, repeated every 8...