Food Effect Studies for Oncology Drug Products

Abstract

Oral antineoplastic agents provide convenience to the patient, but are accompanied by challenges distinct from parenteral cancer treatment. Challenges include a more complex pharmacokinetic profile, with food influencing the absorption of many agents. Standards for evaluating and labeling prandial implications on oral chemotherapy are inconsistent; studies to determine food effects should be conducted early, and potentially often, during drug development with standardization on how rational fasting or fed recommendations are presented in the package insert (PI).

The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study)

“…For all recently approved oral oncolytic agents, the effect of food is being studied as part of the drug's registration process. Many of these oral oncolytic agents have a proven food effect and an alternative dosing strategy could be interesting to investigate . However, only two other oncolytic agents with an alternative dosing strategy combined with food has been studied (e.g., abiraterone and ceritinib) .…”

Reverse Translation of US Food and Drug Administration Reviews of Oncology New Molecular Entities Approved in 2011–2017: Lessons Learned for Anticancer Drug Development

“…Although almost all orally administered NMEs examined fed conditions as a high‐fat, high‐calorie meal only (administered 30 min prior to dosing), there was an emerging trend toward also evaluating alternative meals (low‐fat and moderate‐fat) at different times relative to dosing. As previously described by Parsad et al ., there was variation in how “empty stomach” and “take with food” were expressed in the dosage and administration sections of the labels for applicable NMEs, as well as variation in the level of detail provided about meals in the clinical pharmacology section of the labels. Finally, there were a few examples that illustrated potential consequences of not evaluating food effect during early development (vemurafenib), or not conducting the formal food effect study with the final to‐be‐marketed formulation or one that is not bioequivalent to the final formulation (pomalidomide).…”

Effect of Food on the Pharmacokinetics of Quizartinib

“…[17][18][19][20][21][22][23] For example, midostaurin, an FLT3 inhibitor that also targets multiple kinases, is recommended to be administered with food. 25 In addition, timely communication of food-drug interactions with clear recommendations, including communication with regulatory authorities as well as in publications, can promote proper drug administration. 23 For oral anticancer therapies, adherence to administration recommendations with regard to food can be critical to ensure that target drug concentrations are being achieved and to avoid toxicity.…”