Dose recommendations for anticancer drugs in patients with renal or hepatic impairment: an update

Stefanie D Krens 1 Krens SD Lassche G Jansman FGA et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol. 2019; 20: e200-e207 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar and colleagues have addressed and provided an overview of the topic of dose recommendations in patients with renal or hepatic impairment starting anticancer therapy in their 2019 review. Still, an increasing number of patients with cancer have impaired renal and hepatic function due to ageing and comorbidities. 2 DeSantis CE Miller KD Dale W et al. Cancer statistics for adults aged 85 years and older, 2019. CA Cancer J Clin. 2019; 69: 452-467 Crossref PubMed Scopus (181) Google Scholar , 3 Kontis V Bennett JE Mathers CD Li G Foreman K Ezzati M Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet. 2017; 389: 1323-1335 Summary Full Text Full Text PDF PubMed Scopus (710) Google Scholar With the rise in cancer incidence and the rapidly expanding number of systemic treatment options, one might foresee that dose adjustments in these patients could be required more frequently based on one's renal or hepatic function. Although drug labels provide information on the effect of renal and hepatic impairment on drug exposure, practical advice on how to adjust the starting dose are often insufficient. In 2020, the US Food and Drug Administration (FDA) drafted an updated guidance providing recommendations on the design and conduct of clinical studies in patients with an impaired renal function. 4 US Food and Drug AdministrationGuidance for industry: pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling. https://www.fda.gov/media/78573/downloadDate: 2020 Date accessed: April 12, 2023 Google Scholar More importantly, the FDA addressed how such information should be incorporated in the drug label for use in clinical practice. Although this updated guidance is not yet in effect, practical dosing advice for patients with renal impairment have already been reported more frequently in the drug labels of novel anticancer drugs. Once the guideline is finalised and implemented, this will ensure even further improvement. However, information might still be scattered over different sources and is often scarce for patients with severe renal and hepatic impairment, making it challenging to establish the correct dose. Dose recommendations for anticancer drugs in patients with renal or hepatic impairmentRenal or hepatic impairment is a common comorbidity for patients with cancer either because of the disease itself, toxicity of previous anticancer treatments, or because of other factors affecting organ function, such as increased age. Because renal and hepatic function are among the main determinants of drug exposure, the pharmacokinetic profile might be altered for patients with cancer who have renal or hepatic impairment, necessitating dose adjustments. Most anticancer drugs are dosed near their maximum tolerated dose and are characterised by a narrow therapeutic index. Full-Text PDF