To fast or not to fast? How food could impact on the absorption of kinase inhibitors and its economical value
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18-12-2007
14:34
Pagina 129
Oncol Rev (2007) 1:129–130 DOI 10.1007/s12156-007-0016-2
Camillo Porta
EDITORIAL
To fast or not to fast? How food could impact on the absorption of kinase inhibitors and its economical value
Presently, cancer patients receiving oral kinase inhibitors are suggested to take the drug with an empty stomach or, in the case of drugs such as Sorafenib which are administered twice daily, at least following a lowfat meal. This paradigm, however, has been recently challenged by a study, presented at the 2007 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), which suggested that the dual VEGFR and Her-2 inhibitor Lapatinib could be more readily absorbed if taken with food, and particularly with a high-fat meal. As a result of such an increased bioavailability of the drug, 500 mg of Lapatinib taken with food, may be as effective as 1250 mg (i.e., the presently FDA approved dose) without food. Besided being di per se intiguing, such an observation could have, at least theoretically, a profound impact on the future of targeted therapies for cancer, especially from an economic viewpoint. Indeed, as correctly stressed by Mark Ratain and Ezra Cohen in a commentary recently published on the pages of the Journal of Clinical Oncology [1], a cut by at least 60% in the dose of Lapatinib could lead to
a striking reduction of treatmentrelated costs, which could be estimated, at least for the case of Lapatinib, in around 1,700 US$ per month. In an era where economical considerations represent more and more frequently an issue, especially considering the costs of newer targeted agents, which can be as high as 8.000 € per month, the possibility of reducing the dose of a single drug just relying on pharmacokinetic considerations, without losing therapeutic efficacy, could be an appealing attempt to lower treatment-related cost, or else, to allow the use of promising kinase inhibitor combinations, otherwise economically unaffordable. Furthermore, Lapatinib dosing with food could also lead to the presence of less unabsorbed drug in the gut, thus leading to a consequent reduction in the incidence of diarrhea, a major side-effect of Lapatinib treatment [2]; such an hypothesis, however, seems unlikely based on the same observations reported at the ASCPT meeting. The possibility of reducing both costs and toxicity, provocativelly raised by Ratain and Cohen, have stimulated a lot of controversy, as clearly demonstrated by the number
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18-12-2007
14:34
Pagina 130
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of commentary letters on the above topic, which appeared on the pages of the same Journal of Clinical Oncology [2-6]. For example, in above commentary [1], the Authors suggested that even greater cost savings might be achieved by drinking grapefuit juice with food, to further boost bioavailability, a suggestion that clearly goes against a large body of experimental as well as clinical evidence demonstrating that grapefuit juice can greatly alter bioavailability due to multiple effects on metabolic en
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