Clinical significance of coadministration of moderate to strong CYP enzyme inhibitors with doxorubicin in breast cancer patients receiving AC chemotherapy

Abstract

Introduction

Cytochrome P450 (CYP) enzyme inhibitors may increase the toxicity of many chemotherapies. Medication databases classify doxorubicin coadministration with CYP2D6 or CYP3A4 inhibitors as either a major interaction or contraindication. This study assessed the incidence of toxicity secondary to doxorubicin given with or without CYP enzyme inhibitors in breast cancer patients receiving doxorubicin and cyclophosphamide.

Methods

This retrospective study included female breast cancer patients treated with doxorubicin and cyclophosphamide (AC). Patients were divided into three arms: no moderate or strong CYP inhibitor interactions, moderate or strong CYP2D6 inhibitor interactions, or moderate or strong CYP3A4 inhibitor interactions. Primary outcomes included incidence of doxorubicin-associated toxicity, unplanned medical visits, chemotherapy treatment delays, and doxorubicin dose reductions. The secondary endpoint was time to toxicity.

Results

There were 171 patients included (n = 20 patients in the CYP2D6 inhibitor group and n = 15 in the CYP3A4 inhibitor group). Neither CYP inhibitor group showed a difference in incidence of hepatotoxicity, cardiotoxicity, myelotoxicity, moderate/severe nausea, or treatment delays. Compared to the no CYP inhibitor group, the CYP2D6 inhibitor group experienced a higher incidence of unplanned medical visits (45% vs. 19.4%; p = 0.023) and more frequent doxorubicin dose reductions (30% vs. 7.2%; p = 0.006). The CYP3A4 inhibitor group did not differ from the no CYP inhibitor group for these outcomes.

Conclusions

CYP inhibitors, particularly CYP2D6 inhibitors, may affect doxorubicin tolerability, as seen in this study by an increased incidence of unplanned medical visits and doxorubicin dose reductions.