IntroductionCytochrome 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.MethodsThis 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.ResultsThere 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.ConclusionsCYP 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.

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中强CYP酶抑制剂与阿霉素联合用药对接受AC化疗的乳腺癌患者的临床意义

简介细胞色素 P450 (CYP) 酶抑制剂可能会增加许多化疗的毒性。药物数据库将阿霉素与 CYP2D6 或 CYP3A4 抑制剂联合用药分类为主要相互作用或禁忌症。本研究评估了接受阿霉素和环磷酰胺治疗的乳腺癌患者中联合或不联合使用 CYP 酶抑制剂的阿霉素继发毒性的发生率。方法这项回顾性研究包括接受阿霉素和环磷酰胺 (AC) 治疗的女性乳腺癌患者。患者被分为三组：无中度或强度 CYP 抑制剂相互作用、中度或强度 CYP2D6 抑制剂相互作用、或中度或强度 CYP3A4 抑制剂相互作用。主要结局包括阿霉素相关毒性的发生率、计划外就诊、化疗治疗延迟和阿霉素剂量减少。次要终点是出现毒性的时间。 结果 纳入 171 名患者（CYP2D6 抑制剂组 n = 20 名患者，CYP3A4 抑制剂组 n = 15 名患者）。CYP抑制剂组在肝毒性、心脏毒性、骨髓毒性、中度/重度恶心或治疗延迟的发生率上均未表现出差异。与无 CYP 抑制剂组相比，CYP2D6 抑制剂组的计划外就诊发生率更高（45% vs. 19.4%；p = 0.023），阿霉素剂量减少的频率更高（30% vs. 7.2%；p = 0.006） 。对于这些结果，CYP3A4 抑制剂组与无 CYP 抑制剂组没有差异。结论 CYP 抑制剂，特别是 CYP2D6 抑制剂，可能会影响阿霉素的耐受性，正如本研究中所见，意外就诊的发生率增加和阿霉素剂量减少。