Pharmacokinetics of eribulin mesylate in patients with solid tumors receiving repeated oral rifampicin.

AIM: Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that was recently approved for treatment of metastatic breast cancer. The aim of this study was to determine the effect of rifampicin, a CYP3A4 inducer, on the plasma pharmacokinetics of eribulin in patients with solid tumors. METHODS: An open-label, non-randomized phase I study. Patients received intravenous 1.4 mg/m(2) eribulin mesylate on day 1 and 15 and oral rifampicin 600 mg on days 9 to 20 of a 28-day cycle. Pharmacokinetic sampling for determination of eribulin plasma concentrations was performed up to 144 hours following administration. AUC (0-infinity) and C (max) for eribulin exposure without or with co-administration of rifampicin were subjected to an analysis of variance (ANOVA) and corresponding 90% confidence intervals (CI) were calculated. Subsequently, patients were allowed to continue eribulin mesylate treatment with 1.4 mg/m(2) eribulin mesylate on days 1 and 8 of a 21-day cycle. Also the adverse event profile and anti-tumor activity were assessed. RESULTS: Fourteen patients were included and eleven patients were evaluable for pharmacokinetic analysis. Co-administration of rifampicin had no effect on single-dose exposure to eribulin (geometric least square means ratio: AUC (0-infinity) =1.10 [90% CI 0.91 - 1.34] and C (max) = 0.97 [90% 0.81 - 1.17]). The most common treatment-related grade >/= 3 adverse events were grade 3 neutropenia (4/14, 29%), leukopenia and fatigue (both 3/14, 21%) CONCLUSIONS: These results indicate that eribulin mesylate may be safely co-administered with compounds that are CYP3A4 inducers.