TAXOL(R)-Doxorubicin Combination Significantly Improves Survival In Metastatic Breast Cancer/ Large International Trial Defines Emerging First-Line Treatment St

Vienna, Austria (PROTEXT) - The anti-cancer drug TAXOL givenin combination with doxorubicin significantly prolongs mediantime to disease progression and survival in women with metastaticbreast cancer, according to results of a large Phase IIIinternational clinical trial, presented today at the EuropeanConference on Clinical Oncology (ECCO-10). The study enrolled 267 women at 29 sites throughout 9countries in Central and Eastern Europe and Israel over a two-year period. Half of these women were randomized to receive FAC(5-fluorouracil, doxorubicin, cyclophosphamide), a drug regimenconsidered standard in many countries throughout the world forthe first-line treatment of metastatic breast cancer. Whendirectly compared to this control group, women who received theTAXOL/doxorubicin combination achieved significantly longer timeto disease progression, greater response to treatment andsuperior overall survival. "It remains an unfortunate truth that most of the 600,000women diagnosed worldwide each year with breast cancer eventuallywill fight metastatic disease," said Dr. Jacek Jassem, MD, PhD,Professor of Clinical Oncology, Head, Department of Oncology andRadiotherapy, Medical University of Gdansk, Poland and principalinvestigator of the trial. "The aggressive management of diseaseat this stage is one of our greatest clinical challenges in thefight against breast cancer." Dr. Jassem further noted that when metastatic breast cancer isdiagnosed, the purpose of first-line treatment is to blockdisease progression as completely as possible and prolong patientsurvival. "Based on results of this trial, the TAXOL/doxorubicincombination has emerged an important first-line treatmentstrategy against metastatic breast cancer that warrants immediatefurther development." Trial Design and Results Patients enrolled in this study were selected only if they hadno prior chemotherapy for metastatic disease and no priortreatment with anthracyclines (such as doxorubicin or epirubicin)or taxanes for earlier stages of disease. Patients could havereceived one previous nonanthracycline chemotherapy regimen asadjuvant therapy following surgery. Prior adjuvant chemotherapywas reported at randomization in 43% of patients in the AT armand 44% in the FAC arm. Of the 264 women treated in the trial, 131 received theTAXOL/doxorubucin combination (AT) and 133 received 5-fluouroucil, doxorubicin and cyclophosphamide (FAC). Patientswere treated every three weeks for up to eight cycles. Theprimary objective of the study was to determine time to diseaseprogression, a commonly used efficacy endpoint that measures thelength of time from the first day of randomization until the datedisease progression is first noted. Analyses of both time toprogression and overall survival were performed in all randomizedpatients. Median time to progression was significantly superior for ATcompared with FAC (8.3 months vs. 6.2 months). Survival also wassuperior for patients in the TAXOL arm, who achieved mediansurvival of 22.7 months compared to 18.3 months in the FAC arm.This difference represents a 25% improvement in survival time forAT over the standard control arm. An analysis of response ratedemonstrated that 68% of patients in the AT arm experienced afavorable response to treatment, compared to 55% in the FAC arm.Twice as many patients treated with AT achieved a completeresponse, specifically 19% versus 8% of those patients treatedwith FAC. Therapy was reasonably well tolerated in both arms.Neutropenia was the most frequent and severe adverse event forboth regimens, occurring in 99% of patients receiving AT and 94%of patients receiving FAC. This incidence did not translate intoany significant difference in terms of infection (2% vs. 0%) orfebrile neutropenia (8% vs. 5%). Grade 3-4 arthralgia/myalgia(10% vs. 0%), peripheral neuropathy (12% vs. 0%), and diarrhea(2% vs. 0%) were observed more frequently in the AT arm, whilenausea/vomiting was observed more frequently in the FAC arm (8%vs. 18%). Significantly, no congestive heart failure was reportedin patients receiving AT while on study, despite the achievementof maximum cumulative doses of doxorubicin. Cardiotoxicities arethe most important side effect associated with doxorubucin-containing combination regimens. "This trial was carefully designed to assess efficacy in womenwho closely represent the real world of breast cancer patientswho are diagnosed with metastatic disease before receiving anyprior therapy -- or following non-anthracycline adjuvantchemotherapy," said Dr. Jassem. "The results unequivocallydemonstrate, within the context of this clinical trial, thesuperior efficacy and survival achieved by the TAXOL/doxorubicincombination when compared to FAC -- which is considered standardfirst-line treatment for metastatic breast cancer in Central andEastern Europe and in other regions of the world." Breast Cancer and its Treatment Breast cancer is the most common malignancy among women inEurope and is second only to lung cancer as the leading cause ofcancer among women in the United States. Each year an estimated60,000 recorded deaths are attributable to breast cancer and250,000 new cases occur in the E.U. Like all individuals fighting solid tumors, women diagnosedwith breast cancer are at risk for metastatic disease. It is thismicroscopic spread of disease (metastasis) that threatenssurvival, not the breast tumor itself. Breast cancer metastasesoccur when cancer cells spread beyond the original tumor sitethrough the lymphatic and vascular systems to form new, distantareas of cancer, originating from the breast. Local treatmentwith surgery and/or radiotherapy, however radical, will notprevent or control metastases in most women with breast cancer. The threat of metastases and the need to control it, if itoccurs, mandates the use of systemic treatment for breast cancer,frequently more than once if the cancer progresses. Chemotherapytreats the body systemically and can be used to achieve cure,prolong life when cure is not achievable, or to palliatesymptoms. Chemotherapy can be administered in earlier stages ofdisease as neoadjuvant therapy (before surgery), adjuvant surgery(following surgery), and then following a diagnosis of metastaticdisease as first-, second- or third-line therapy. It is estimated that approximately 55,000 women are treatedfor metastatic breast cancer in the E.U. each year. ots OriginalText Service: Medical University of Gdansk - Department ofOncology and Radiotherapy Internet: http://www.newsaktuell.deContact: Jeff Smith, +44-171-282-1246, or Garreth Hayes, +44-171-282-1217, for the Medical University of Gdansk - Department ofOncology and Radiotherapy Company News On-Call:http://www.prnewswire.com/comp/137916.html or fax, 800-758-5804,ext. 137916 Web site: http://www.bms.com

Subscribers please note that material bearing the slug"PROTEXT" is not part of CTK's news service and is not to bepublished under the "CTK" slug. Protext is a commercial serviceproviding distribution of press releases from clients, who areidentified in the text of Protext reports and who bear fullresponsibility for their contents.

PROTEXT