Study Results Demonstrate the Benefit of Early Use of Taxotere in Treatment of Breast Cancer

Findings of a breast cancer study published today in JCO support the addition of Taxotere in neo-adjuvant (prior to surgery) chemotherapy for the treatment of breast cancer. In a study of women with large (3 cm or more) or locally advanced breast cancer, patients given Taxotere following anthracycline-based chemotherapy experienced a better response rate in reduction in the size or disappearance of the tumor than those patients given the anthracycline-based regimen alone. Treatment with an anthracycline-based chemotherapy regimen is currently a standard of care in the neo-adjuvant setting.

The study, conducted at the University of Aberdeen in the UK, found that patients who responded to four cycles of neo-adjuvant chemotherapy with an anthracycline-based regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CVAP) and followed by four cycles of Taxotere, experienced a higher clinical response rate (94% vs. 66%) and a higher complete pathological response rate (34% vs. 16%) than those patients given four additional cycles of the anthracycline regimen. A clinical response refers to the physically observable disappearance or shrinkage of a tumor; a pathological response refers to the microscopic analysis of breast tissue.

“In localized breast cancer, the goal of chemotherapy given prior to surgery is to reduce the size of the tumor, thus increasing the likelihood of breast conservation and improving survival,” said Steven Heys, Professor of Surgical Oncology and Nutritional Oncology, University of Aberdeen, UK. “In this study, patients given docetaxel in addition to an anthracycline-based chemotherapy experienced a better response rate in terms of tumor reduction, which suggests that patients given docetaxel are less likely to have to undergo mastectomy following completion of the chemotherapy. These results strongly support the addition of docetaxel to neo-adjuvant chemotherapy in the treatment of breast cancer.”

Survival Benefit also Demonstrated

Additional data from this study were recently presented at the 24th Annual San Antonio Breast Cancer Symposium in December 2001. According to data presented there, patients who received the neo-adjuvant Taxotere-containing regimen lived significantly longer than patients who did not receive Taxotere. Patients in the CVAP/Taxotere arm achieved a 97 percent three-year survival rate compared to 84 percent in patients in the CVAP/CVAP treatment arm. In addition, the disease-free survival rate at three years was 90 percent in the Taxotere-treated group, compared with 77 percent for patients who did not receive Taxotere.

“While this survival data is promising, and we are encouraged by it, it is important to keep in mind that this is preliminary data and that larger studies will be needed to confirm its significance,” added Dr. Heys.

The study included 104 patients with large or locally advanced breast cancer who demonstrated a clinical response after four initial cycles of CVAP chemotherapy. Of those patients, 52 were randomized to receive four further cycles of CVAP and 52 were randomized to receive four cycles of Taxotere. An additional 55 patients enrolled in the trial failed to demonstrate a response to the initial CVAP therapy and were treated with four cycles of Taxotere. Of these patients, 55 percent (n=26) achieved a clinical response following the four cycles of Taxotere.

Significantly fewer hematologic side effects were experienced by women in the Taxotere arm of the study. In the study, Taxotere patients required less dose reduction due to hematologic toxicity than did patients who received the anthracycline-based regimen.

Breast cancer is the most common type of cancer among women in the United States and is the leading cause of cancer deaths among women ages 40 – 59.

Second Study Shows Promising Results in Treatment of Advanced Head and Neck Cancer

A separate study published in the same issue of JCO showed that a combination of Taxotere and cisplatin is an effective treatment for patients with recurrent or incurable head and neck cancer. The study was designed to assess the anti-tumor activity and toxicity of Taxotere (75 mg/m2 as a 1 hour infusion) plus cisplatin (75 mg/m2 as a 30 minute infusion) in patients with recurrent or incurable squamous cell carcinoma (SCCHN) of the head and neck.

In this phase II, multicenter study, patients given the Taxotere/cisplatin combination regimen experienced a 40 percent overall response rate and a median survival rate of 9.6 months. The current standard treatment for patients with recurrent SCCHN is a cisplatin-based combination therapy with 5-fluorouracil (5-FU), which is associated with significant mucosal toxicity and a longer administration time. Investigators concluded that the Taxotere/cisplatin combination regimen has an acceptable safety profile and may offer advantages over the current standard treatment.

“The overall response rate and median survival demonstrated with the docetaxel/cisplatin combination is somewhat higher than what we’ve see with the current standard regimen,” said Bonnie S. Glisson, M.D., Professor of Medicine, M. D. Anderson Cancer Center, Houston Texas. “In addition, we saw less mucosal toxicity and a shorter, more convenient administration than we see with the standard cisplatin/5-FU combination regimen. These are important findings that we hope to confirm in a larger, phase III comparative trial, which is already underway.”

Study participants received Taxotere at 75mg/m2 as a one-hour infusion and then cisplatin at 75 mg/m2 as a 30 minute infusion in an outpatient setting; cycles were repeated every 21 days. Although the incidence of severe neutropenia (low white blood cell count) was high (80%), only 17 percent of patients experienced severe infection associated with grade 4 neutropenia or required intravenous antibiotics for neutropenic fever without documented infection.

Squamous cell carcinoma accounts for the vast majority of the 60,000 cases of head and neck cancers diagnosed annually in the United States. If diagnosed at an early stage, SCCHN often responds to therapy, with a five-year survival rate of 70 to 90 percent following standard therapy. However, approximately two thirds of patients are diagnosed at an advanced stage. Prognosis for advanced SCCHN is poor, and patients diagnosed with recurrent or incurable disease have a median length of survival of only six months with conventional chemotherapy.

About Taxotere

Taxotere, a drug in the taxoid class of chemotherapeutic agents, inhibits cancer cell division by essentially “freezing” the cell’s internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing cancer cells from dividing and resulting in cancer cell death. Taxotere is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. The most common severe side effects associated with Taxotere include low blood cell count, fatigue, fluid retention and mouth sores. The most common non-severe side effects included hair loss, numbness and tingling, skin and nail changes, nausea and diarrhea. These side effects are generally reversible and manageable. A premedication regimen with corticosteroids is recommended in order to prevent or reduce hypersensitivity and fluid retention. Taxotere is not appropriate therapy for patients with significant liver impairment or a low white blood cell count. For more information about on-going clinical trials, please call 1-800-RxTrial.