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Abstract #485
TAXOTERE(r) PLUS ADRIAMYCIN (r) OUTPERFORMS STANDARD COMBINATION IN WOMEN WITH METASTATIC BREAST CANCER
Significantly Longer Time to Disease Progression and Higher Response Rate Without Corresponding Increase in Cardiac Toxicity
Atlanta, Ga, May 15, 1999 -- Combination treatment with the chemotherapeutic agents Taxotere(r) (docetaxel) and Adriamycin(r) (doxorubicin) produces a significantly longer time to progression and higher response rate than the combination of Adriamycin and Cytoxan(r) (cyclophosphamide) when used as first-line chemotherapy in women with metastatic (spreading) breast cancer, according to a large, multicenter worldwide phase III study presented at the annual meeting of the American Society of Clinical Oncology. Importantly, the longer time to progression and higher response rate with Adriamycin/Taxotere occurs even in patients with a poor prognosis.
The data also show that the combination does not cause an increase in cardiotoxicity (damage to the heart).
"Unfortunately, once breast cancer has spread to other parts of the body, median survival is generally less than two years," commented 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 long term survival for metastatic breast cancer patients has been elusive, traditional therapies have been aimed primarily at alleviating symptoms of the disease. Today treatments are being evaluated with the goal of improving both the quality and duration of remissions. Our findings demonstrate that the Adriamycin/Taxotere combination has shown a significant advantage over the standard first-line combination and, therefore, may be a beneficial regimen to patients with advanced disease." Study Design
The study included 429 women with documented metastatic breast cancer who had not undergone prior chemotherapy for metastatic disease and had not received a prior anthracycline-containing regimen as adjuvant and/or neo-adjuvant chemotherapy.
Participants were randomized to treatment with either Taxotere, 75 mg/m2 plus Adriamycin, 50 mg/m2, or Adriamycin, 60 mg/m2, plus Cytoxan, 600 mg/m2. The regimen was repeated every three weeks for a maximum of eight cycles without the use of prophylactic colony-stimulating factors (agents used to strengthen the body's ability to fight infection) or antibiotics, except following an episode of neutropenia (a low white blood cell count).
The median age of the study population at enrollment was 53 years, and the median disease-free interval from adjuvant therapy was 25 months. Forty-two percent of patients had received prior adjuvant chemotherapy, 62 percent had visceral metastases, and 41 percent had metastatic involvement of three or more organs. All subjects had normal renal and hepatic function adequate bone marrow reserves, and acceptable cardiac function as determined by their left ventricular ejection fraction. Significant Findings
In this study, the Adriamycin/Taxotere (AT) combination demonstrated a significantly longer time to disease progression than Adriamycin/Cytoxan (AC) at 37 weeks vs. 32 weeks. At 12 months, 28% of AT treated patients were without disease progression vs.19% for AC treated patients.
The overall response rate was significantly higher than the response seen with standard AC therapy (60% vs. 47%). Eleven percent of patients had a complete response, and 49 percent had a partial response. In contrast, seven percent of patients in the AC group had a complete response, and 40 percent had a partial response.
In clinical studies of cancer therapy, the overall response rate is defined as the partial response rate plus the complete response rate. A complete response is a complete disappearance of all clinical and X-ray signs of cancer, while a partial response refers to a 50 percent or greater decrease in measurable tumor size. Response rates were also analyzed in three separate subgroups which play an important role in determining how well a patient will respond to treatment: patients with visceral or liver involvement, patients with multiple sites of disease, and patients who had undergone prior adjuvant therapy. In all cases, the AT combination was associated with higher response rates. "This finding is especially noteworthy, as these groups of patients have a poor prognosis with current standard therapy which often includes an anthracycline-containing regimen," Dr. Nabholtz said.
Safety Profile
Both combination therapies were generally well-tolerated. Neutropenia with or without fever was more common in the AT combination, but did not compromise relative dose intensity (full dose potential) and did not cause death from sepsis (the absorption of pathogens in the bloodstream) or significant infection. The remaining toxicities were comparable between the two treatment groups.
Of particular note, the rate of cardiac toxicity for the two treatment combinations did not exceed that expected with the total cumulative doses of Adriamycin given. "Damage to the heart is a known side effect of repeated doses of Adriamycin and can cause permanent, and occasionally fatal, injury. In addition, some agents, when combined with Adriamycin have been shown to increase cardiac toxicity. It is vital to discover new combinations that are both safe and effective which can provide meaningful benefit to patients with metastatic breast cancer," Dr. Nabholtz noted. Metastatic Breast Cancer
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 half of all breast cancer patients will eventually develop recurrent disease. The incidence of breast cancer has been increasing steadily since the 1930s. It is the most common malignancy affecting women, accounting for 18 percent of all female cancers, and over 780,000 new cases are reported each year worldwide. In the United States alone, approximately 180,000 women each year will be diagnosed with breast cancer. It is the number one cause of death among women in their forties; roughly 20% of all deaths in this age group result from breast cancer.
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