Antineoplastics are characterised by a narrow therapeutic index, complicated by inter-individual pharmacokinetic variability especially in the setting renal and/or hepatic dysfunction (RHD). Despite RHD being a common occurrence in cancer patients, existing ‘gold standard’ guidelines for dose modification of antineoplastics are inconsistent and based on minimal evidence. Recent medication events attributed to inappropriate antineoplastic dose adjustments in RHD have further highlighted the lack of a national standardised approach to dosing.
A literature review of dose modification in RHD was undertaken using primary research papers and international guidelines e.g. Cancer Care Ontario, National Cancer Institute. Inclusion criteria described the dosing of antineoplastic for patients with RHD at baseline. Classifications of impairment and approaches to dose modification were identified and compared to the current eviQ recommendations.
Sixty-one primary papers were identified, along with three international guidelines. Large variability in RHD classification and dose modifications approaches were found. No consistency existed between sources including eviQ i.e. no dose adjustment was recommended in one source whilst in another the drug was contraindicated in RHD. Although the newer antineoplastics were evaluated in RHD as part of regulatory requirements, older agents lack such evaluations. Therefore with limited data, dose reductions are unable to be confidently applied to these older antineoplastics.
Dosing challenges for antineoplastics in RHD are confounded by the differing measures of organ dysfunction, limited pharmacokinetic studies and the subsequent lack of consensus in dose adjustment approaches. A national multidisciplinary expert group will advise the development of a standardised approach to enhance the safety and best practice for the delivery of antineoplastics in patients with RHD.