Breast Cancer Drug Lapatinib Works Best With Food
July 23, 2007
A study by Dartmouth researchers presented at the March 2007 annual meeting of the American Society for Clinical Pharmacology and Therapeutics showed that taking the breast cancer drug lapatinib with food results in greater absorption of the drug. Normally patients take lapatinib on an empty stomach.
The primary objective of the Dartmouth study was to quantify the effect of meals with high and low fat content on lapatinib. Twenty-seven pts (17 female, 10 male) with a variety of solid tumors were enrolled in a Phase I oncology study. Each patient received a single 1500 mg oral dose of lapatinib on three different occasions, randomly assigned to conditions of fasting overnight or following a high or low fat breakfast. Blood samples were collected up to 48 hours after lapatinib administration and plasma lapatinib concentrations were measured. Upon completion of this assessment, patients could continue to receive 1500 mg lapatinib daily.
The data showed that lapatinib absorption significantly increased compared to the fasted state, by approximately 3- and 4- fold when given with a low-fat and high-fat meal, respectively. These changes in relative bioavailability were positively related to the fat and/or caloric content of the meal.
Nandi Reddy, MBBS , a fellow in clinical pharmacology at Dartmouth, was the lead author of the study, and Lionel Lewis, MD, professor of medicine and of pharmacology and toxicology at Dartmouth, was the senior author.
"A Phase I, Open-label, Three Period, Radomized Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics (PK) of Lapatinib in Cancer Patients," N. J. Reddy, MD , R. B. Cohen, MD, B. Whitehead, BS, K. M. Koch, PhD, A. Stead, PhD, A. P. Beelen, MD, L. D. Lewis, MBBCh, MD, Dartmouth Hitchcock Medical Center, Fox Chase Cancer Center, GlaxoSmithKline, GlaxoSmithKline, Lebanon, NH; Clinical Pharmacology and Therapeutics 81 Supplement 1, pg 16-17, abstract P!-15 (2007).