Cut Cancer Drug Costs By Exploring Food Interactions

Allison Gandey

July 18, 2007

July 18, 2007 — Could interactions between cancer drugs and food represent a novel approach to improving available treatment options? New studies exploring how certain foods alter absorption or delay the breakdown of drugs may have an interesting flip side — they may eventually cut medication costs and increase benefits, explain researchers in an article published online July 16, 2007 in the Journal of Clinical Oncology. "As we enter an era of targeted anticancer agents with a monthly cost measured in thousands of dollars," University of Chicago oncologists Mark Ratain, MD, and Ezra Cohen, MD, write, "we should view drug-drug or drug-food interactions as opportunities to lower costs."

The new commentary was inspired by a study presented in March at the 2007 annual meeting of the American Society for Clinical Pharmacology and Therapeutics. In the small phase 1 study, lead author Nandi Reddy, MD, from Dartmouth Hitchcock Medical Center, in Lebanon, New Hampshire, showed that taking lapatinib with food, instead of on an empty stomach as suggested by the product label, increases the relative bioavailability.

Lapatinib (Tykerb, GlaxoSmithKline) is an oral dual tyrosine kinase inhibitor. It is indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy, including an anthracycline, a taxane, and trastuzumab.

"Simply by changing the timing — taking this medication with a meal instead of on an empty stomach — we could potentially use 40% or even less of the drug," Dr. Ratain said in a news release. "Since lapatinib costs about $2900 a month, this could save each patient $1740 or more a month."

Food and Beverages Affect Drug Bioavailability

Adding a glass of grapefruit juice to a meal, which may also increase plasma concentrations, according to the lapatinib package insert, could increase the savings to 80%, the authors suggest, minus the cost of food and juice. "We expect that a 250-mg lapatinib pill accompanied by food and washed down with a glass of grapefruit juice may yield plasma concentrations comparable to 5 pills on an empty stomach," Dr. Ratain said.

The effect of grapefruit juice on oral bioavailability may be due in part to furanocoumarins. The authors are currently conducting a prospective phase 1 trial of the combination of grapefruit juice and oral sirolimus (Rapamune, Wyeth). Dozens, if not hundreds, of drugs should be studied in this way, the authors suggest. "If we understood the relationship between, say, grapefruit juice and common drugs, such as the statins, which are taken daily by millions of people to prevent heart disease, we could save a fortune in drug costs," Dr. Cohen said in a news release. "And patients would get a little vitamin C to boot."

These results are not surprising given that food often increases a drug’s bioavailability, the authors note. So why does the lapatinib package insert, including the patient information, indicate that lapatinib should be taken at least 1 hour before or at least 1 hour after food? "The answer is fairly straightforward," they write. "This is how the sponsor conducted its pivotal phase 3 trial." Investigators apparently did not know the result of the food effect study. Therefore, the officially recommended dose must match the dose used in the trial, which was 5 tablets (250 mg each) taken while fasting.

The authors point out the recommendation is even more problematic in light of the required colabeling with capecitabine, which is administered twice daily with food and has its own dosing issues. "Obviously, it would be much easier for patients to take all of their pills at 1 time with food, as opposed to having to deal with the complexity of taking one set of pills fasting and one set of pills with food," they note.

There would also be potential clinical benefit to using a lower dose of lapatinib with food, the authors add. Diarrhea is a major adverse effect of lapatinib, and it is suggested that this effect is due to unabsorbed drug, given that its frequency is better correlated with dose than with plasma concentration. Using a lower dose with food would markedly reduce the amount of unabsorbed drug and therefore theoretically also reduce the frequency and severity of diarrhea.

Drs. Ratain and Cohen conclude, "The rapidly escalating price of medications has provided incentives to explore pharmacological approaches to lower the costs of drugs."

J Clin Oncol. 2007. Published online July 16, 2007.



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