Dew, Concerning ADH -- by blocking the activity of the enzyme DPD, eniluracil should increase the toxicity of 5-FU. It also looks like eniluracil "temporarily blocks the activation of 5-FU into the metabilites responsible for its anti-cancer activity". That doesn't sound like a particularly promising combination of effects (greater toxicity and possibly less efficacy). ADH says that they're trying to get around these problems by altering the dosing levels/schedules. Have the ADH studies completed to date indicated that they're on the right track? The fact that Glaxo previously abandoned eniluracil is not reassuring. Thanks for your insights.
From the ADH press release - >>> GSK’s clinical development program for the combination of 5-FU and eniluracil met with success in early development. However, three Phase III trials undertaken by GSK failed and development was stopped. Since then, Adherex has generated data which provide a new understanding of the mechanism of action of eniluracil - namely that eniluracil not only inhibits the breakdown of 5-FU, it also temporarily blocks the activation of 5-FU into the metabolites responsible for its anti-cancer activity. As a result, the Company has identified three factors that are necessary to optimize the combination of eniluracil and 5-FU: 1) the dose of eniluracil, 2) the ratio between the eniluracil and 5-FU dosages, and 3) the schedule of administration of the two drugs. <<<
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