Phase I/II Pharmacokinetic Study of Pemetrexed and Epirubicin in Patients with Locally Advanced or Metastatic Breast Cancer

BackgroundPemetrexed and epirubicin are each active in patients with advanced/metastatic breast cancer (MBC). This phase I/II study evaluated these drugs as a combination regimen.Patients and MethodsWomen with locally advanced or MBC were enrolled. Pemetrexed 400–600 mg/m2 and epirubicin 60–90 mg/m2 were administered on day 1 every 21 days. The recommended phase II dose was evaluated in a 2-stage design.ResultsPhase I enrolled 34 patients and evaluated 5 dose levels. Dose-limiting toxicities were neutropenia and febrile neutropenia. Patients received a median of 7.5 cycles (range, 1–8 cycles), and promising efficacy (partial response [PR], 32%; stable disease [SD], 50%) was observed. Pharmacokinetics of pemetrexed was unchanged when combined with epirubicin. Selected phase II regimen (pemetrexed 600 mg/m2 and epirubicin 75 mg/m2) was administered to 22 patients (median, 4.5 cycles; range 1–13 cycles). Five patients experienced a PR (23%), and 10 experienced SD (46%). This response was below the predefined efficacy requirements for subsequent enrollment, and accrual was stopped. Median time to progression was 5.3 months (95% CI, 3.1-8.9 months), and median time to treatment failure was 3.5 months (95% CI, 2.6-5.9 months).ConclusionThe regimen is safe but cannot be recommended as first-line chemotherapy in advanced breast cancer because of the low response rate.