CHICAGOIf a drug's bioavailability is increased by food, then why not take the drug with food, allowing for a possible reduction in dose? Mark J. Ratain, MD, and Ezra E. Cohen, MD, of the University of Chicago, posed this question in a commentary in the Journal of Clinical Oncology (August 10, 2007).
Specifically, they looked at lapatinib (Tykerb), which was FDA approved last March for use in patients with metastatic HER2-positive breast cancer in combination with capecitabine (Xeloda).
A randomized crossover food-effect study showed that the bioavailability of lapatinib is greatly increased by food, especially a high-fat meal. So why does the lapatinib package insert indicate the drug should be taken at least 1 hour before, or at least 1 hour after, food?
"The answer is fairly straightforward," the authors said. "This is how the sponsor conducted its pivotal phase III trial. . . . Thus, the officially recommended dose must match the dose used in the pivotal trial, which was five 250-mg tablets taken fasting." This is especially burdensome for patients, since they are also taking capecitabine, which must be taken with food, they noted.
"The economic implications of this food-effect study are particularly remarkable," Drs. Ratain and Cohen said.If lapatinib were taken with food, they hypothesized, two 250-mg tablets daily would offer the same efficacy as the recommended five 250-mg tablets fasting. "At the current price of $2,900 per month, a cost savings of 60% or $1,740 per month would be realized if the drug were taken with food," they wrote, referring to this as "the value meal."
The two authors did not suggest that physicians should begin prescribing the lower dose with food but called for a study of the issue, one they do not anticipate the sponsor of lapatinib to initiate. But they did propose a remedy for the sponsor:development of a new, more expensive 500-mg formulation, which would be dosed with food rather than fasting. "This would be slightly easier for patients than taking two 250-mg tablets with food," they said, "but more importantly it could allow the sponsor to salvage the market that would be lost through widespread adaptation of the so-called value meal,based dosing of lapatinib."