Women with Metastatic Breast Cancer Respond to Taxotere

WOMEN WITH METASTATIC BREAST CANCER RESPOND TO TAXOTERE IN COMBINATION WITH DOXORUBICIN AND CYCLOPHOSPHAMIDE

Regimen Not Associated With Increase in Cardiac Toxicity

San Antonio, Texas, December 13, 1998 -- The addition of TaxotereÆ (docetaxel) , an active single chemotherapy agent, to the combination of AdriamycinÆ (doxorobicin) and CytoxanÆ (cyclophosphamide) is an effective and safe first-line therapy for women with metastatic (spreading) breast cancer, according to a study presented at the 21st Annual San Antonio Breast Cancer Symposium. Notably, the combination did not cause an increase in cardiotoxicity, a side effect often caused by the cumulative dose of doxorubicin.

"Once breast cancer becomes metastatic, the disease is essentially incurable, and the median survival following diagnosis of metastases is less than two years," said Jean-Marc A. Nabholtz, MD, Chairman of the Northern Alberta Breast Cancer Program and Senior Medical Oncologist at the Cross Cancer Institute in Edmonton, Canada. "Because established therapies for late-stage disease remain largely palliative, it is important to examine new combinations. Our results in this trial strongly suggest that combining Taxotere with Adriamycin/Cytoxan enhances overall activity without increasing side effects.î

Adriamycin and Cytoxan are chemotherapy agents often used together as primary and first-line treatment for patients with breast cancer. First-line chemotherapy refers to follow-up treatment for metastatic breast cancer previously untreated with chemotherapy for metastatic disease.

The Phase II multicenter study included 55 patients with previously untreated metastatic breast cancer patients who received Adriamycin, 50 mg/m2, as an intravenous (IV) bolus followed by Cytoxan, 500 mg/m2, as an IV bolus, and Taxotere, 75 mg/m2, one hour later as a one-hour infusion. The regimen, referred to as TAC, was repeated every three weeks. Patients who had received prior chemotherapy for metastatic disease or an anthracycline-containing regimen as adjuvant (chemotherapy used along with surgery and radiation) and/or neo-adjuvant (preoperative) chemotherapy were not eligible for enrollment.

At the start of the trial, the median age was 53 years. Thirty two percent of patients had received prior adjuvant chemotherapy. Fifty four percent of patients had three or more organs involved.

Of 47 patients evaluable for response, the overall response rate was 77 percent.

In clinical studies of cancer therapy, the overall response rate is defined as the partial response rate plus the complete response rate. A partial response refers to a 50 percent or greater decrease in measurable tumor size, while a complete response is a complete disappearance of all clinical and X-ray signs of cancer.

Responses occurred at all sites of breast cancer involvement, and was also high in patients with liver, lung, visceral, or bone metastases.

The median duration of response and time to disease progression were 59 weeks and 47 weeks, respectively. With a median follow-up to date of 23 months, the median survival has not yet been reached. Overall, 57 percent of patients were alive at two-year follow-up.

The combination therapy was relatively well-tolerated. The most common adverse effects included brief episodes of neutropenia (low white blood cell count) and fever without a documented infection, which were effectively treated with antibiotics and did not necessitate a decrease in the dose intensity of any of the study drugs. Severe fluid retention occurred in only one patient.

Only two patients developed congestive heart failure despite having been exposed to a relatively high cumulative dose of Adriamycin; one of them died as a result. "This finding is impressive considering the fact that some other chemotherapeutic agents, when used in combination with Adriamycin, can increase the risk of cardiotoxicity," Dr. Nabholtz commented.

Breast cancer is abnormal cell growth originating in glandular breast tissue. If not diagnosed early, these cells invade surrounding tissue and spread through the blood and lymph node system. Common sites of breast cancer metastases include the bone, lungs, liver, brain, and lymph nodes. Although many women are initially treated successfully, approximately 50 percent of breast cancer patients will eventually develop recurrent disease.

Breast cancer is the most common malignancy in women, accounting for 18 percent of all female cancers, and over 570,000 new cases are reported each year worldwide. In the United States alone, the disease is newly detected in approximately 180,000 women annually and is the leading cause of death among women aged 40-50 years; roughly 20% of all deaths in this population are related to breast cancer.

For more information, contact: David Kirkham, Director of Media Relations, Alberta Cancer Board: 403-437-0859

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