"These results reaffirm that ELLENCE is an integral component of treatment of patients with node positive breast cancer," said William Gradishar, MD, Associate Professor of Medicine in the Division of Hematology and Medical Oncology at Northwestern University Medical School. "Patients stand to benefit from the significant outcome advantages delivered from these two ELLENCE-based regimens."
The data from this large phase III randomized, multi-center clinical trial that evaluated nearly 2,000 patients were presented by Dr. Henri Roche on behalf of a consortium of French and Belgian oncologists and showed that patients receiving sequential treatment achieved a disease free survival rate of 78.3% in the sequential arm and 73.2% in the FEC 100 only arm. In addition, patients treated with the sequential regimen achieved overall survival of 90.7% and those treated with FEC alone achieved overall survival of 86.7%.
This independent study, coordinated by the Fédération Nationale des Centres de Luttes Contre le Cancer (FNCLCC), was partially funded by Pharmacia Corporation, now part of Pfizer Inc. Pfizer is the manufacturer of ELLENCE.
Study Results and Design
Between June 1997 and March 2000, 1999 patents were recruited in 83 French and Belgian locations to participate in this large phase III randomized, multi-center clinical trial. Women with node-positive breast cancer were randomly assigned to receive either an adjuvant chemotherapy regimen containing six cycles of only FEC 100 or three cycles of FEC 100 followed by three cycles of docetaxel. G-CSF was not administered prophylactically but was added in cases of febrile neutropenia or delayed neutrophil recovery. Radiotherapy was mandatory for all patients and tamoxifen was given after completion of chemotherapy for 5 years if tumors were hormone receptor (HR) positive.
Patient characteristics were well balanced between the two arms: median age was 50 years, conservative surgery was performed in 52% of patients, 39% of tumors were grade III, 79% were HR positive, 21% of patients were HR negative and 62% of patients had one to three positive lymph nodes. The prescribed treatment was completed in 98% of patients in the FEC 100 plus docetaxel arm and 99% of patients in the FEC 100 only arm. In addition, the relative dose intensity was maintained in 96% of the FEC 100 arm and 98% in the FEC 100 plus docetaxel arm.
At a median follow-up of 60 months, data show the FEC 100 followed by docetaxel arm delivered superior disease-free and overall survival compared to the FEC 100 arm. In patients receiving FEC 100 followed by docetaxel, the disease-free survival rate was 78.3% vs. 73.2% for patients receiving FEC 100 (P=0.0122), representing a 17% reduction in the risk of relapse. In addition, overall survival rate was 90.7 percent (P=0.0135) in the sequential arm vs. 86.7 % in the FEC 100 arm, representing a 23% reduction in the risk of death.
In addition to the positive survival data resulting from this study, very few patients experienced serious side effects such as heart damage or neutropenia. The most frequent toxicities reported in the study were hematologic. Grade 3-4 NCI-CTC hematologic toxicities included neutropenia (9.4% vs. 7.3%), febrile neutropenia (1.6% vs. 2.9%) and mucositis (0.8% vs. 1.3%) for the FEC 100 and FEC 100 followed by docetaxel arms, respectively. 14.8% and 8.9% of the patients in the FEC 100 arm and in the FEC 100 plus docetaxel arm, respectively, required addition of G-CSF during their treatment. No significant differences were seen between the two arms relative to infection, anemia and thrombocytopenia. Edema and nail disorders were more common in the docetaxel containing arm.
Four patients (0.4%) developed congestive heart failure in the FEC 100 arm, a recognized potential complication of this type of treatment.
About Breast Cancer and ELLENCE
Breast cancer is the second leading cause of cancer death among women. It is estimated that 213,910 women in the United States will be diagnosed with breast cancer in 2004 and more than 40,921 women will lose their lives to the disease.
ELLENCE is an anthracycline cytotoxic anti-cancer agent and is the first chemotherapy approved by the FDA for use as a component of adjuvant therapy in the treatment of early-stage resectable breast cancer that has spread to the lymph nodes. It works in part by uncoiling the strands of genetic material that make up DNA (genetic information of a cell), which prevents cells from reproducing.
ELLENCE has a generally manageable side effect profile. In several Phase III clinical trials, the most common side effects were nausea, vomiting, mouth sores and hair loss. Because chemotherapy can damage the blood-producing cells of the bone marrow, patients may experience low blood cell counts. Some patients may experience a severe reduction in white blood cells. Rarely, heart failure or a type of leukemia can occur.
Full prescribing and safety information, including black box warnings, can be found at http://www.pfizeroncology.com.
About Pfizer
Pfizer Inc is the world's leading research-based pharmaceutical company, providing a broad range of human and animal pharmaceuticals, as well as consumer products. In 2003, the company committed $7.1 billion to R&D, involving its scientists in more than 33 major research projects across 10 major therapeutic categories. With 120,000 employees worldwide, Pfizer is also involved in the global community, donating hundreds of millions of dollars of medicine to the developing world and to expand drug access in the United States.