Investigation of the efficacy of imidazolyl ethanamide pentandioic acid (IEPA) to reduce chemotherapy-induced myelosuppression (CIM) in breast cancer patients.

Abstract

e23098 Background: Neutropenia is a major toxicity of myelosuppressive chemotherapy (CTX). Treatment and prophylaxis of CTX-induced neutropenia with granulocyte colony-stimulating factors is mainly recommended in patients with high risk of febrile neutropenia. IEPA, a hemoprotective small molecule for oral use, may constitute a safe alternative. The main objective of the study was to assess the efficacy of IEPA in reducing CIM in breast cancer patients. Methods: Randomized, double-blind, placebo-controlled, parallel group study in female adults diagnosed with invasive breast cancer receiving epirubicin/cyclophosphamide CTX. Patients took one tablet daily of IEPA 100 mg or placebo starting 5 days prior to the first CTX cycle until 3 days prior to the second CTX cycle. Two batches of study medication were used sequentially in the study. Hematologic and other variables were tightly measured during the first CTX cycle. Results: After no significant treatment effect was observed in the total study results, post-hoc analyses revealed a significant batch effect. Treatment with Batch 1 IEPA was superior to placebo in treating CIM (Table). Conclusions: Although the presence of a batch effect precludes final conclusions and calls for a formulation optimization of the compound, the efficacy of Batch 1 IEPA in reducing CIM consistent with prior non-clinical and clinical studies invites further investigation of the hemoprotective properties of IEPA. Area over the curve (AOC) integrates extent and duration of decreased absolute neutrophil counts [(ANC/nL)*days] below thresholds corresponding to grade 1 (ANC < 2.0x10^9/L) and 3 neutropenia (ANC < 1.0x10^9/L); CI: confidence interval; LS: least squares; DN3: duration of grade 3 neutropenia in [days]. Clinical trial information: NCT02692742. [Table: see text]