FDA advisers back epirubicin for early breast cancer SILVER SPRING, MD, Jun 08 (Reuters Health) - Advisers to the US Food and Drug Administration (FDA) on Monday urged approval of Pharmacia & Upjohn's epirubicin hydrochloride (Ellence) to treat locally advanced, but not metastatic, breast cancer. The Oncologic Drugs Advisory Committee voted unanimously to back epirubicin, an anthracycline, for adjuvant treatment of node-positive breast cancer following surgical resection. But it voted 6-3 against approval as a first-line treatment for metastatic disease. Overall, epirubicin-treated patients with metastatic disease had slightly longer survival, but both they and early-stage patients had a higher risk of congestive heart failure and leukemia. Although some patient advocates at the meeting argued for approval, others said they were not impressed with epirubicin. "I see it has some survival benefit, but with significant toxic effects, so I don't see what's so exciting to the patient," said Sandra Zook-Fischler, the panel's patient representative. Ann Fonfa of The Annie Appleseed Project in New York said, "I don't see any significant change in survival, and as a cancer patient, long term survival is what I care about." Fonfa chided the panel for not demanding a longer survival benefit for proof of efficacy. "You're spending millions of dollars and you're not getting anything that's any better for cancer patients. Please, please aim higher, I beg you," she said. Epirubicin has been approved in 80 countries. Upjohn first applied for FDA approval in 1984, but was subsequently turned down because it did not have sufficient data, said the agency. After Upjohn merged with Pharmacia, the company reapplied in December 1998, using new data. In these new trials--seven of which were submitted to the FDA--epirubicin was studied in a regimen with cyclophosphamide and fluorouracil (CEF) and compared to a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) in both stage II and III breast cancer. In the main stage II study, conducted from 1989 to 1993 at 37 sites in Canada, 356 premenopausal women with axillary node-positive breast cancer received CEF with epirubicin of 120 mg/meter squared, and got prophylactic antibiotic therapy, every four weeks for six cycles. A similar number of patients received CMF for the same duration. Patients were ineligible if they received previous hormonal or cytotoxic therapy, or had distant metastases. They had to have a left ventricular ejection fraction of >45%. The primary endpoint was relapse-free survival. The 5-year relapse-free survival rate was 62% in the epirubicin group compared with 53% in the CMF group. Results were similar in a second study, conducted at 20 sites in France from 1990-93. Seventy-seven percent of the epirubicin patients survived five years, compared to 70% of CMF patients. There was a 29% reduction in the risk of death, said Pharmacia & Upjohn's Langdon Miller. In the major trial in metastatic breast cancer, 223 women received CEF with 100 mg/meter squared of epirubicin, while 237 patients received CMF. Patients were allowed to have received previous therapy. Overall, 57.4.% of the CEF group responded compared to 44.7% of the CMF group. The median time to tumor progression was 8.7 months for CEF patients, compared with 6.3 months for CMF patients. There was no statistically significant difference in overall survival, with the median being 20.1 months for the CEF patients compared with 18.2 months for CMF patients. Across the seven studies, there was a higher incidence of leukemia and cardiotoxicity in epirubicin patients. In the early-stage study, the rate of cardiotoxicity was 3.4% in the epirubicin group compared with 1.1% in the CEF group. The effect was even more pronounced in metastatic patients, with corresponding rates of 13% and 4%. In the early stage study, acute myelogenous leukemia occurred in four epirubicin patients,1.1%, and acute lymphocytic leukemia occurred in one patient. Grade 3/4 anemia and neutropenia were also higher for epirubicin patients. In the early-stage trial, 95% of the epirubicin group had grade 3/4 neutropenia, compared with 60% of the CMF patients. Nausea and vomiting were higher also, FDA reviewer Susan Honig said, but serotonin-specific antiemetics were not available during the studies. Thanks to Reuters Health Information Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.