Phase I study of pemetrexed (ALIMTA) and epirubicin in patients with locally advanced or metastatic breast cancer

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Abstract 290.Background.Pemetrexed is a novel antifolate that inhibits TS, DHFR, and GARFT. Both pemetrexed and epirubicin have documented efficacy in breast cancer.Objectives.To determine the maximum tolerated dose (MTD) of pemetrexed and epirubicin in combination in patients with advanced breast cancer.Methods.Pemetrexed and epirubicin were sequentially administered as 10 min infusions, on day 1 of a 21-day cycle. Folic acid and vitamin B12 were given to reduce incidence and severity of toxicities reported in earlier pemetrexed studies.Preliminary results.Twenty-two female patients ages 35-74 years (median 54 years) with PS 0-2 were enrolled. Five patients had received prior neoadjuvant (1) or adjuvant (4) chemotherapy. Patients received 1-8 cycles (median 6) of study drugs. Of 116 cycles administered, there were 12 dose reductions (G4 neutropenia) and 10 dose delays (transaminitis [5], neutropenic fever [1], and scheduling conflicts [4]). G3/4 neutropenia (15/22) was the most common hematologic toxicity. Neutropenic fever was the only G3/4 non-hematologic toxicity [1]. One patient discontinued due to recurrence of G4 neutropenia after 2 dose reductions. MTD was reached at dose level 3 with dose-limiting toxicities (DLTs) in 3/12 pts (neutropenic fever [1] and G4 neutropenia 5 days [2]). To date, 8 PRs and 5 stable disease (SD) have been reported among 14 patients with mature follow up. TABLEConclusion.This combination is well tolerated. Although MTD was reached at dose level 3, enrollment at pemetrexed 600 mg/m2 and epirubicin 75 mg/m2 is ongoing to establish the best recommended phase II regimen.

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