Chair of Clinical Pharmacology and Clinical Toxicology, Institute for Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen; Pharmacy, University Hospital Erlangen; Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg (EMN), Erlangen.
Dtsch Arztebl Int. 2019 Nov 15;116(46):775-782. doi: 10.3238/arztebl.2019.0775.
Many oral anti-cancer drugs have come onto the market in the past 20 years. For example, kinase inhibitors, such as the BCR-ABL and BRAF inhibitors, have markedly improved the treatment of chronic myeloid leukemia and melanoma. In this review, we discuss the special challenges posed by poor adherence, drug-drug interactions with other substances, and side effects, among other problems, and the ways in which these challenges can be met.
A selective search was carried out in PubMed for original and review articles on the safety of new oral anti-cancer drugs. Guidelines and current Summaries of Product Characteristics (SmPC) were also considered in the analysis.
Review articles have pointed out numerous safety concerns with oral anti-cancer drugs. One of these is adherence, on which highly variable figures are available (with mean non-adherence rates ranging from 0 to 54%). The absorption of approximately half of these drugs is influenced by the patient's diet, and that of approximately 20% by gastric pH (Caution: proton-pump inhibitors may influence bioavailability). 70% of the active substances are metabolized primarily by CYP3A4, which means that their pharmacokinetics can be altered by grapefruit juice and CYP3A4 modulators. The prevention, detection, and treatment of side effects (which can be gastrointestinal, cutaneous, cardiovascular, or other) is a highly important matter.
The increasing use of oral anti-cancer drugs confronts patients and treatment teams with special challenges. To optimize treatment outcomes, a multidisciplinary approach should be taken, involving physicians, pharmacists, and nurses. To improve medication safety, medication and side-effect management should be performed, and adherence should be regularly checked and systematically encouraged.
在过去的 20 年里,许多口服抗癌药物已经上市。例如,激酶抑制剂,如 BCR-ABL 和 BRAF 抑制剂,显著改善了慢性髓性白血病和黑色素瘤的治疗效果。在这篇综述中,我们讨论了由于药物依从性差、与其他物质的药物相互作用以及副作用等问题所带来的特殊挑战,以及如何应对这些挑战。
在 PubMed 上进行了选择性搜索,以获取有关新的口服抗癌药物安全性的原始和综述文章。在分析中还考虑了指南和当前的产品特性摘要(SmPC)。
综述文章指出了许多口服抗癌药物的安全性问题。其中之一是药物依从性,其数据差异很大(平均不依从率范围为 0 至 54%)。大约一半的这些药物的吸收受到患者饮食的影响,大约 20%的药物吸收受到胃 pH 值的影响(注意:质子泵抑制剂可能会影响生物利用度)。70%的活性物质主要由 CYP3A4 代谢,这意味着其药代动力学可能会被葡萄柚汁和 CYP3A4 调节剂改变。预防、检测和治疗副作用(可能是胃肠道、皮肤、心血管或其他副作用)是非常重要的事情。
口服抗癌药物的使用越来越多,这给患者和治疗团队带来了特殊的挑战。为了优化治疗效果,应采取多学科方法,涉及医生、药剂师和护士。为了提高用药安全性,应进行用药和副作用管理,并定期检查和系统地鼓励药物依从性。