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Rich66 · 05-11-2012, 05:16 PM

http://www.medicalnewstoday.com/releases/224062.php

About Eniluracil/5-FU/leucovorin

Eniluracil is a mechanism-based inactivator of DPD, the enzyme that rapidly breaks down 5-FU. Accordingly, eniluracil increases the 5-FU elimination half-life from about 15 minutes to 5 hours and enables 5-FU to be administered orally, making it 100% orally bioavailable. In addition, eniluracil prevents the formation of α-fluoro-β-alanine (F-Bal), the 5-FU-breakdown product. F-Bal appears to cause hand-foot syndrome, neurotoxicity, and also decreases the antitumor activity of 5-FU in laboratory animals. Furthermore, because DPD is present in variable levels, the highly variable and nonlinear pharmacokinetics of 5-FU become predictable and linear when DPD is inactivated by eniluracil in cancer patients.

The weekly regimen used in the current Phase 2 trial is based on a Phase 1 eniluracil/5-FU/leucovorin trial that produced durable tumor responses and no hand-foot syndrome in advanced colorectal cancer patients who were refractory to intravenous 5-FU/leucovorin. In a similar Phase 2 study with capecitabine, no tumor responses occurred and 87% of the patients experienced hand-foot syndrome, a painful condition that may require dosing interruptions and dose reductions. The eniluracil/5-FU/leucovorin regimen for metastatic breast cancer uses two modifications of the Phase 1 regimen. The eniluracil dose is increased to 40 mg to minimize neurotoxicity and is administered the night before 5-FU to prevent high eniluracil:5-FU ratios that interfere with the antitumor activity.

05-11-2012, 05:16 PM	#1
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	eniluracil/5-FU/leucovorin http://www.medicalnewstoday.com/releases/224062.php About Eniluracil/5-FU/leucovorin Eniluracil is a mechanism-based inactivator of DPD, the enzyme that rapidly breaks down 5-FU. Accordingly, eniluracil increases the 5-FU elimination half-life from about 15 minutes to 5 hours and enables 5-FU to be administered orally, making it 100% orally bioavailable. In addition, eniluracil prevents the formation of α-fluoro-β-alanine (F-Bal), the 5-FU-breakdown product. F-Bal appears to cause hand-foot syndrome, neurotoxicity, and also decreases the antitumor activity of 5-FU in laboratory animals. Furthermore, because DPD is present in variable levels, the highly variable and nonlinear pharmacokinetics of 5-FU become predictable and linear when DPD is inactivated by eniluracil in cancer patients. The weekly regimen used in the current Phase 2 trial is based on a Phase 1 eniluracil/5-FU/leucovorin trial that produced durable tumor responses and no hand-foot syndrome in advanced colorectal cancer patients who were refractory to intravenous 5-FU/leucovorin. In a similar Phase 2 study with capecitabine, no tumor responses occurred and 87% of the patients experienced hand-foot syndrome, a painful condition that may require dosing interruptions and dose reductions. The eniluracil/5-FU/leucovorin regimen for metastatic breast cancer uses two modifications of the Phase 1 regimen. The eniluracil dose is increased to 40 mg to minimize neurotoxicity and is administered the night before 5-FU to prevent high eniluracil:5-FU ratios that interfere with the antitumor activity.