Sombogaard F, Franssen E J F, Terpstra W E, Kerver E D, van den Berk G E L, Crul M
Department of Clinical Pharmacy, Onze Lieve Vrouwe Gasthuis Hospital, Oosterpark 9, 1090 HM, Amsterdam, The Netherlands.
Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
Int J Clin Pharm. 2018 Oct;40(5):1402-1408. doi: 10.1007/s11096-018-0620-1. Epub 2018 Jun 12.
Background The combination of combined active antiretroviral therapy (cART) with chemotherapy in the treatment of lymphoma in human immunodeficiency virus (HIV)-positive patients has improved the overall survival of these patients. However, drug-drug interactions between antineoplastic agents and the antiretroviral agents non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) can occur by influencing the activity of the CYP3A4 enzyme. So far, little is known about the clinical relevance of this interaction: the effect on the efficacy and toxicity of the chemotherapy. Also, there is no general consensus which cART is preferable in combination with antineoplastic drugs. Objective To compare PI-based with NNRTI-based cART on the efficacy and toxicity of chemotherapy in lymphoma patients. Setting The Onze Lieve Vrouwe Gasthuis, located in Amsterdam, The Netherlands. Method A retrospective observational cohort study including all patients with HIV and lymphoma over a 10-year period. Clinical outcome (response to chemotherapy and survival) and toxicity of chemotherapy (renal, hepatic and bone marrow toxicity as well as dose reduction, treatment delay and discontinuation) was compared in patients with PI based and NNRTI-based cART. Main outcome measure: Response to chemotherapy and survival. Results Patients using PI-based cART (n = 22) had a significantly lower 1 year survival compared to NNRTI-based cART (n = 21). No significant differences were observed in reaching complete remission after chemotherapy. No overall significant differences in toxicity and discontinuation of the chemotherapy were observed. However, there was a trend towards more severe bone-marrow toxicity in patients with PI-based cART. In addition, patients with PI-based cART received earlier dose-reduction and treatment delay, indicating increased toxicity in PI-treated patients. Conclusion This retrospective study shows that PI-based cART is inferior in combination with chemotherapy to NNRTI-based cART: a lower 1 year survival is observed and dose-reduction and treatment delay occur earlier, possibly based on an earlier onset of toxicity.
背景 联合抗逆转录病毒疗法（cART）与化疗相结合用于治疗人类免疫缺陷病毒（HIV）阳性患者的淋巴瘤，已改善了这些患者的总体生存率。然而，抗肿瘤药物与抗逆转录病毒药物非核苷类逆转录酶抑制剂（NNRTIs）和蛋白酶抑制剂（PIs）之间可能会发生药物相互作用，通过影响细胞色素P450 3A4（CYP3A4）酶的活性。到目前为止，关于这种相互作用的临床相关性知之甚少：对化疗疗效和毒性的影响。此外，对于哪种cART与抗肿瘤药物联合使用更优尚无普遍共识。目的 比较基于蛋白酶抑制剂（PI）的cART与基于非核苷类逆转录酶抑制剂（NNRTI）的cART对淋巴瘤患者化疗疗效和毒性的影响。地点 位于荷兰阿姆斯特丹的翁泽利夫弗劳韦加斯豪伊斯医院。方法 一项回顾性观察队列研究，纳入了10年间所有HIV合并淋巴瘤的患者。比较了接受基于PI的cART和基于NNRTI的cART的患者的临床结局（对化疗的反应和生存率）以及化疗毒性（肾毒性、肝毒性和骨髓毒性以及剂量减少、治疗延迟和停药情况）。主要结局指标：对化疗的反应和生存率。结果 与接受基于NNRTI的cART的患者（n = 21）相比，接受基于PI的cART的患者（n = 22）1年生存率显著更低。化疗后达到完全缓解方面未观察到显著差异。化疗毒性和停药情况未观察到总体显著差异。然而，接受基于PI的cART的患者有出现更严重骨髓毒性的趋势。此外，接受基于PI的cART的患者更早出现剂量减少和治疗延迟，表明PI治疗的患者毒性增加。结论 这项回顾性研究表明，基于PI的cART与化疗联合使用时不如基于NNRTI的cART：观察到1年生存率更低，且剂量减少和治疗延迟更早出现，可能是基于更早出现的毒性。
