Relationships Between Food Effects, Patient Adherence to Treatment, and Pharmacokinetics of Oral Anticancer Drugs

e17614 Background: Taking oral anticancer drugs with food has the potential to influence their bioavailability and exposure. The objective of this literature review was to identify oral anticancer drugs with food restrictions in the label, to assess the effects of food on their pharmacokinetics, and to explore food restrictions as a potential barrier to adherence. Methods: A review of U.S. Food and Drug Administration (FDA) labels identified oral anticancer drugs with food restrictions. The effect of food on exposure was quantified by comparing the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) in fed and fasted states. A systematic literature review identified studies investigating the impact of food restrictions on adherence to treatment; sources included PubMed, EMBASE, and Cochrane Reviews. Results: Among 14 oral anticancer drugs approved by the FDA since 2009, 7 have food restrictions: 4 must be taken without food, 2 must be taken with food, and 1 must be taken consistently with or without food. The AUC ratio (fed/fasted) of oral anticancer drugs ranged from 0.78 with axitinib to 10.0 with abiraterone (median = 1.20); the Cmax ratio ranged from 0.4 with everolimus to 17.0 with abiraterone (median = 1.00). A limited number of relevant food restriction studies were identified: 5 of anticancer drugs and 7 of noncancer drugs. Overall, these studies suggest that food restrictions are burdensome, confusing, and associated with reduced adherence to treatment. In one cancer study, 43% of patients who received agents with significant food effects reported that they did not consider the timing of meals before dosing, and 23% were unaware of food restrictions (Muluneh B, et al. ASCO 2012;6042). The incidence of missed doses was also found to be higher for anticancer drugs with food restrictions than those without (Gupta S, et al. ASH 2011;2077). Conclusions: A significant variation in systemic exposure observed with oral agents is related to food intake. Food restrictions are often difficult to comply with and are potentially associated with reduced adherence. Patients receiving oral anticancer drugs with food restrictions must be closely monitored for compliance.