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Food–drug interactions could lower required dose of anticancer drug

Taking lapatinib (Tykerb, GlaxoSmithKline) on a full stomach could reduce the required dose by 60%, suggests a new commentary published online in the Journal of Clinical Oncology. Mark Ratain and Ezra Cohen, both of the University of Chicago (USA), analyzed recent findings (presented at the March 2007 meeting of the American Society for Clinical Pharmacology and Therapeutics), which revealed that the concentration of lapatinib in the body was significantly higher when taken with food. If taken with a high-fat meal, patients could potentially reduce their required dose by 60%. The drug was approved earlier this year by the US FDA for use in HER2-positive breast cancer patients, following a successful Phase III trial. The approved dose, 1250 mg (five 250 mg tablets) taken on an empty stomach, has been demonstrated to be safe and effective and currently costs US$2900 per month. The commentary proposes that 500 mg with food could be as effective as 1250 mg without food. This means that patients or insurers could potentially save US$1740 (60%) a month by switching to a lower dose taken in combination with food. In addition, it has been suggested that taking lapatinib with grapefruit juice (together with food) could reduce the required dose by as much as 80%. Grapefruit juice is known to delay the breakdown of many drugs and is currently being investigated by the authors with sirolimus (Rapamune, Wyeth). The authors stress that patients should not change any doses based on such findings, as lower doses in combination with food have not been tested in clinical trials. “The first word of caution is ‘do not try this at home’. The last thing we want is to have patients take their drug with food or change the dose on their own. That could be potentially dangerous,” warned Cohen. However, the authors do note that researchers should investigate food–drug interactions as potential benefits, rather than avoiding them. “As we enter an era of ‘targeted’ anticancer agents with a monthly cost measured in the thousands of dollars, we should view drug–drug or drug–food interactions as opportunities to lower costs,” explained the authors in their commentary.