Mark Ratain and Ezra Cohen may not be making a lot of friends in the pharmaceutical industry these days, but the folks at the Florida Department of Citrus are smitten. And, if they are successful in their efforts to use grapefruit juice to raise the potency of cancer drugs, patients may want to take their grapefruit puckered lips and give them a big kiss.

Ratain and Cohen are both oncologists at the University of Chicago. Their war on the high prices of cancer drugs began simply enough when something on a poster presentation at the 2007 American Society for Clinical Pharmacology and Therapeutics caught Ratain's eye. It showed that if someone takes the drug lapatinib on a high fat meal, the peak concentration of the drug more than triples.

The instructions on the drug, a breast cancer treatment marketed under the brand name Tykerb, is to take five 250 mg. tablets or a total of 1,250 mg. at least one hour before or after eating. The dosing instructions of five tablets without food are what they are because that's the way the clinical trial that led to its approval happened to be structured. Though not the intent of the trial, the two oncologist argue in a comment today in the Journal of Clinical Oncology that the data suggested eating a value meal at McDonald's with the drug could cut the needed dose to just two 250 mg. pills. This would save 60 percent of the drug cost—a reduction to $1,160 per month, down from $2,900 a month.

Big Returns
For Ratain, he sees it as using pharmacology to combat the high cost of these drugs. He said in the case of lapatinib, it's modestly priced by 2007 standards, but that many other cancer drugs could cost as much as $5,000 a month.

"The more they increase the price of oral drugs, the more people will be tantalized by the thought of using pharmacology to reduce the necessary dose," he said. "If you can demonstrate you get comparable pharmacokinetics and comparable efficacy, that's how you would prescribe the drug."

The two doctors caution that patients should not experiment on their own with such food-drug interactions. Instead, they said what's needed are clinical trials that would enable physicians to predict how individual patients will take up and metabolize specific drugs in the presence of certain foods.

Since it is unlikely that drug companies would do this for their own products, what the doctors would like to see is patient advocacy groups fund trials to establish just that. Ratain said such trials could be done on a relatively small scale. He expects a pharmacokinetic study would require 15 to 20 patients and an efficacy trial could provide a reasonably good answer with 100 to 200 patients. The total cost for such trials would be about $4 million to get the data needed to apply to the FDA for a label change.

Think of the math this way. If peak sales of lapatinib are projected at $1 billion, a $4-million investment in clinical trials that establish the safety and efficacy of cutting the dose by 60 percent if taken with food could translate into a $600 million a year savings for patients. He said no pharmaceutical company would hesitate spending $4 million for a potential return of $600 million a year.

Exploiting Interactions
Ratain and Cohen would like to see someone conduct such a study on lapatinib, but they are also doing some work of their own. The two are involved in an early-stage clinical trial using the drug sirolimus (rapamycin) with eight ounces of grapefruit juice a day to cut the needed dose to treat various cancers. Grapefruit juice is known to inhibit the activity of CYP3A, a critical enzyme in the metabolism of sirolimus and many other drugs. By inhibiting the enzyme the breaks the drug down, it remains available in the body to act on the disease.

The study is being funded by the University of Chicago and the two hope of have data to present at next year's American Society of Clinical Oncology meeting. They haven't heard from pharmaceutical companies yet. But they did hear from the Florida Department of Citrus, which is now supplying grapefruit juice to them and even testing it first to make sure it has adequate concentrations of the needed active ingredients.

"We should be looking at these interaction issues and using them to our advantage," said Cohen. "Instead of avoiding them we should exploit them."