A narrative review of genetic factors affecting fluoropyrimidine toxicity
William H. Gmeiner
Abstract
OBJECTIVE: Our objective is to document progress in developing personalized therapy with fluoropyrimidine drugs (FPs) to improve outcomes for cancer patients and to identify areas requiring further investigation. BACKGROUND: , which encodes the rate-limiting enzyme for pyrimidine degradation are at very high risk. Other genetic factors affecting risk for 5-FU toxicity, including miR-27a, are under investigation. METHODS: Literature used to inform the text of this article was selected from PubMed.gov from the National Library of Medicine while regulatory documents were identified via Google search. CONCLUSIONS: , ENOSF1, p53) also affect 5-FU toxicity. Functional testing for deficient pyrimidine catabolism {defined as [U] >16 ng/mL or [UH2]:[U] <10} is being implemented in France and has demonstrated utility in identifying patients with elevated risk for 5-FU toxicity. Therapeutic drug monitoring (TDM) from plasma levels of 5-FU during first cycle treatment also is being used to improve outcomes and pharmacokinetic-based dosing is being used to increase the percent of patients within optimal area under the curve (AUC) (18-28 mg*h/L) values. Patients maintained in the optimal AUC range experienced significantly reduced systemic toxicities. As understanding the genetic basis for increased risk of 5-FU toxicity becomes more refined, the development of functional-based methods to optimize treatment is likely to become more widespread.