Occhipinti Mario, Brambilla Marta, Galli Giulia, Manglaviti Sara, Giammaruco Maristella, Prelaj Arsela, Ferrara Roberto, De Toma Alessandro, Proto Claudia, Beninato Teresa, Zattarin Emma, Lo Russo Giuseppe, Gelibter Alain Jonathan, Simmaco Maurizio, Preissner Robert, Garassino Marina Chiara, De Braud Filippo, Marchetti Paolo
Thoracic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133 Milan, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
J Pers Med. 2021 May 18;11(5):424. doi: 10.3390/jpm11050424.
(1) Background. The onset of a drug-drug interaction (DDI) may affect treatment efficacy and toxicity of advanced non-small-cell lung cancer (aNSCLC) patients during epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) use. Here we present the use of Drug-PIN (Personalized Interactions Network) software to detect DDIs in aNSCLC patients undergoing EGFR-TKIs. (2) Methods. We enrolled patients with Stage IV aNSCLC already treated with or candidates to receive EGFR-TKIs, in any line; ECOG PS 0-2; taking at least one concomitant drug. Cancer treatments, concomitant drugs, and clinical and laboratory data were collected and inserted in Drug-PIN. (3) Results. Ninety-two patients, median age of 68.5 years (range 43-89), were included. In total, 20 clinically relevant DDIs needing medical intervention in a total of 14 patients were identified; the 14 major DDIs were related to a high-grade interaction between TKIs and SSRIs, antipsychotics, antiepileptics, H2-receptor antagonist and calcium antagonists. A negative association between statin intake and PFS was identified ( = 0.02; HR 0.281, 95% CI 0.096-0.825). (4) Conclusions. This is the first retrospective study assessing the prevalence of DDIs, the clinical need for medical intervention and the impact of concomitant drugs on EGFR-TKIs survival in aNSCLC.
(1) 背景。药物相互作用（DDI）的发生可能会影响晚期非小细胞肺癌（aNSCLC）患者在表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗期间的疗效和毒性。在此，我们展示了使用Drug-PIN（个性化相互作用网络）软件来检测接受EGFR-TKI治疗的aNSCLC患者中的药物相互作用。(2) 方法。我们纳入了IV期aNSCLC患者，这些患者已经接受过或可能接受任何线的EGFR-TKI治疗；东部肿瘤协作组（ECOG）体能状态评分为0-2；正在服用至少一种伴随药物。收集癌症治疗、伴随药物以及临床和实验室数据，并输入到Drug-PIN中。(3) 结果。共纳入92例患者，中位年龄68.5岁（范围43-89岁）。总共识别出20种需要医疗干预的具有临床相关性的药物相互作用，涉及14例患者；这14种主要的药物相互作用与TKI与选择性5-羟色胺再摄取抑制剂（SSRI）、抗精神病药物、抗癫痫药物、H2受体拮抗剂和钙拮抗剂之间的高度相互作用有关。他汀类药物摄入与无进展生存期（PFS）之间存在负相关（P = 0.02；风险比[HR] 0.281，95%置信区间[CI] 0.096-0.825）。(4) 结论。这是第一项评估aNSCLC患者中药物相互作用的患病率、医疗干预的临床需求以及伴随药物对EGFR-TKI生存影响的回顾性研究。
