Liver function testing is a routine part of pre-assessments and ongoing monitoring with the application of cancer chemotherapy. In respect to dosing many cancer drugs are subject to hepatic elimination and given their generally low therapeutic index there is considerable angst over excessive toxicity, or alternatively were dose modifications have been applied, under treatment.
The role of hepatic metabolism is generally established during early phase testing in subjects with normal organ function and historically patients with liver impairment have been excluded from controlled trials. These together leave an informational gap. Equally liver function tests are not precision tools for quantifying hepatic drug clearance. In response to the perceived risk of excess toxicity dose modifications have been variously proposed. These were frequently arbitrary, derived from small studies or retrospective data, and in several cases reported a long time ago and then perpetuated through literature. Alternatively, for some drugs guidance to omit a drug is because the trial did not allow patients with that level of impairment. Dose modification guidance is available in approved prescribing information, institutional guidelines, and systematic reviews. Notably there are areas of practical difference between these resources.
In considering dose modification, particularly in the setting of curative intent, an understanding of how recommendations were derived and what evidence was considered is particularly useful. This remains a difficult area of medicines management.