• Katja Schlichtig, Pauline Dürr, Frank Dörje, and Martin F Fromm.
• 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.

BackgroundMany 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.MethodsA 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.ResultsReview 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.ConclusionThe 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.

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