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

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.