Sharma Manvi, Vadhariya Aisha, Chikermane Soumya, Gopinathan Suma, Chavez-MacGregor Mariana, Giordano Sharon H, Johnson Michael L, Holmes Holly M
Department of Pharmacy Administration, The University of Mississippi, Oxford, MS, USA.
Department of Pharmaceutical Health Outcomes and Policy, University of Houston, Houston, TX, USA.
Drugs Aging. 2019 Apr;36(4):341-354. doi: 10.1007/s40266-019-00640-5.
Oral chemotherapy use is increasing due to new drug approvals as well as the convenience of the administration of oral drugs. This increased use also raises concern regarding drug-drug interactions (DDIs) with concomitantly administered drugs, resulting in loss of therapeutic effect, decreased tolerability, and/or increased toxicity.
The objective of this study was to review existing evidence of the clinical impact of DDIs with oral chemotherapeutic agents.
A comprehensive search of literature using PubMed was conducted in April 2018 for studies of DDIs associated with oral chemotherapy. Included studies were in English. We included randomized clinical trials, observational studies, and case reports evaluating a DDI between any oral chemotherapy drug and any other drug. Included studies needed to have at least one outcome of clinical relevance potentially attributed to the DDI, for example, effects on survival or toxicity. The quality of the articles was determined using published metrics appropriate for the study design.
There were 2626 studies identified in the initial search, of which 35 met all eligibility criteria. These included 15 retrospective cohort studies, 16 case reports or case series and four post hoc analyses of clinical trials. Among these, DDIs contributed to a statistically significant change in a clinical outcome in 12 studies. Eight of these studies evaluated overall survival and progression-free survival and found that the presence of the DDI was associated with reduced survival.
Our findings suggest that more real-world studies evaluating the association between oral chemotherapy DDIs and clinical outcomes are needed. The adverse clinical outcomes due to DDIs may be a reason for treatment failures and therapy discontinuation.
由于新药获批以及口服药物给药方便，口服化疗的使用正在增加。这种使用的增加也引发了对与同时使用的药物发生药物相互作用（DDIs）的担忧，这可能导致治疗效果丧失、耐受性降低和/或毒性增加。
本研究的目的是综述关于口服化疗药物药物相互作用临床影响的现有证据。
2018年4月使用PubMed对文献进行了全面检索，以查找与口服化疗相关的药物相互作用研究。纳入的研究为英文。我们纳入了评估任何口服化疗药物与任何其他药物之间药物相互作用的随机临床试验、观察性研究和病例报告。纳入的研究需要至少有一个可能归因于药物相互作用的临床相关结局，例如对生存或毒性的影响。使用适合研究设计的已发表指标确定文章质量。
在初步检索中确定了2626项研究，其中35项符合所有纳入标准。这些研究包括15项回顾性队列研究、16项病例报告或病例系列以及4项临床试验的事后分析。其中，12项研究中药物相互作用导致临床结局有统计学显著变化。其中8项研究评估了总生存期和无进展生存期，发现药物相互作用的存在与生存期缩短有关。
我们的研究结果表明，需要更多评估口服化疗药物相互作用与临床结局之间关联的真实世界研究。药物相互作用导致的不良临床结局可能是治疗失败和治疗中断的原因。
