Adherex Reports First Patient Enrolled In Phase 2 Study Of Eniluracil In Metastatic Breast Cancer
Adherex Technologies Inc. (TSX:AHX)(PINK SHEETS:ADHXF), a biopharmaceutical company focused on the development of eniluracil and 5-fluorouracil today announced the enrollment of the first patient in the Phase 2 clinical trial for Metastatic Breast Cancer comparing the oral regiment of Eniluracil + 5-Fluorouracil (5-FU) and Leucovorin versus Capecitabine (Xeloda®).
The comparative study intends to enroll 140 patients at approximately 20 clinical sites in the United States and Russia in the next 12 to 14 months. It plans to enroll 80 patients in the eniluracil/5-FU/leucovorin arm and 60 in the capecitabine arm. All agents are administered orally as tablets. Eligible patients have been previously treated with an anthracycline and a taxane during neoadjuvant, adjuvant, or first-line therapy for metastatic disease. Patients, who have disease progression while being treated with capecitabine, may be eligible to crossover to receive eniluracil/5-FU/leucovorin treatment.
“The goal of the trial is to show superior antitumor activity and tolerability for eniluracil/5-FU/leucovorin,” said Tom Spector, PhD, Chief Scientific Officer of Adherex and principal inventor of the treatment. “After many years of clinical research, we now believe that we have the optimal doses and schedule to achieve these goals.”
The primary endpoint of the trial is progression-free survival. The secondary endpoints include the overall toxicity (including hand-foot syndrome), antitumor response rate, disease control rate, duration of response, and time-to-treatment response. Patients receiving eniluracil (40 mg)/5-FU (30 mg/m2)/leucovorin (30 mg) are treated once per week for three consecutive weeks per month. Patients receiving capecitabine are treated with 1000 mg/m2 every 12 hours for 14 days every three weeks.
“It is an absolute privilege to be a part of this international study,” said Dr. Edgardo Rivera, Medical Director for Banner MD Anderson Cancer Center and Principal Investigator for the study, “I look forward to how this may impact the future treatment of Metastatic Breast Cancer.”
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 ?-fluoro-?-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.
About Metastatic Breast Cancer
Breast cancer is the second leading cause of cancer related death among women, according to the National Cancer Institute. In 2010, NCI estimated that 207,090 women were diagnosed with breast cancer, while 39,840 women likely died from the disease. FDA-approved therapies used to treat late-stage, refractory breast cancer include Xeloda (capecitabine) for patients with breast cancer resistant to paclitaxel and anthracycline-containing chemotherapy; Ixempra (ixabepilone) for patients with late-stage disease after failure of an anthracycline, taxane and Xeloda; Ixempra plus Xeloda for patients with late-stage disease after failure of anthracycline- and taxane-based chemotherapy; Halaven (eribulin mesylate) for patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage disease.
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Adherex Technologies Inc.