The treatment with Docetaxel ( Taxotere ) significantly improved overall survival and median time to disease progression compared with Paclitaxel in women with advanced breast cancer whose cancer had progressed after previous treatment with an anthracycline-based therapy.

The study showed a statistically significant median overall survival of 15.4 months for Docetaxel versus 12.7 months for Paclitaxel ( HR, 1.41; p=0.03 ).

Docetaxel and Paclitaxel are agents in a class known as taxanes, which are commonly used to treat women with advanced breast cancer.

This study randomized 449 patients with locally advanced or metastatic breast cancer after prior failure with an anthracycline-containing chemotherapy regimen from 53 U.S. and Canadian centers.

The patients received either Docetaxel ( 100 mg/m2, 1-hour intravenous infusion every 21 days ) or Paclitaxel ( 175 mg/m2, 3-hour intravenous infusion every 21 days ) – each drug given at the dosage and schedule as approved by the FDA ( Food and Drug Administration ).

This trial demonstrates that, among all patients who were assigned to receive either Docetaxel or Paclitaxel ( intent to treat analysis ), Docetaxel conferred significantly longer median time to progression than Paclitaxel ( 5.7 months vs. 3.6 months, p<0.0001 ).

Among patients evaluable for response ( tumor shrinkage ), those who received Docetaxel had significantly higher response rates ( 37.0% vs. 26%, p=0.02 ) and significantly longer median duration of response ( 7.5 months vs. 4.6 months, p=0.01 ), than those who received Paclitaxel. When response was evaluated on an intent-to-treat basis, the overall response rate was higher for Docetaxel ( 32.0% vs. 25.0%, p=0.10, ns ) compared with Paclitaxel. However, this difference was not significant.

" This is the first clinical trial to directly compare these extensively used taxanes. Preclinical and laboratory evidence suggested that Docetaxel and Paclitaxel are different," said Stephen E. Jones, at Baylor-Sammons Cancer Center, Dallas, Texas.

Patients in the study continued to receive study drug as long as they were responding to treatment.
Patients received a median of six cycles of Docetaxel compared to a median of four cycles of Paclitaxel.

The use of G-CSF, a bone marrow growth factor that may be administered to reduce febrile neutropenia in patients receiving myelosuppressive chemotherapy, was only permitted following an initial episode of grade 4 leukopenia or neutropenia persisting longer than seven days, or when associated with fever.

The adverse events reported in the study were consistent with those previously observed in Docetaxel studies and are not different from those observed in routine clinical practice. The incidence of treatment-related hematologic and nonhematologic adverse events was greater for Docetaxel than for Paclitaxel; however, quality of life scores were not statistically different between treatment groups over time.

The randomized, multi-center, phase III trial enrolled 449 women.
Two hundred twenty-five women with a median age of 56 years received Docetaxel while 224 patients, average age 54, were administered Paclitaxel.

Primary endpoints of the study were objective response and toxicity.
Secondary endpoints included overall survival, duration of response, time to progression (time without the cancer growing) and quality of life. Quality of life scores were similar between treatment arms over time despite an increased incidence of grade 3/4 toxicities, including neutropenia ( 93.3% vs. 54.5% p<0.001 ), infections ( 9.9% vs. 1.8% p<0.001 ), diarrhea ( 5.4% vs. 0.5% p<0.001 ) and edema ( 6.8% vs. 0.5% p<0.001 ) in women who received Docetaxel.

Quality of life was assessed using the Functional Assessment of Cancer Therapy ( FACT ) measurement system for breast cancer, FACT-B. The questionnaire is designed to assess quality of life including the emotional, functional, physical and social well being of patients. The women completed the questionnaire prior to treatment, after cycle 4 and at the end of the treatment.

Taxotere is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and it is also approved in combination with Doxorubicin and Cyclophosphamide ( TAC regimen ) for the adjuvant treatment of patients with operable, node-positive breast cancer.

Taxotere is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer ( NSCLC ) in combination with Cisplatin, who had not received prior chemotherapy, and it also is approved for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy.
In addition, the FDA has approved Taxotere for use in combination with Prednisone as a treatment for men with androgen-independent metastatic prostate cancer.

Taxotere treatment can cause serious, physically limiting, and potentially life-threatening side effects, such as infection, low blood-cell counts, allergic reaction, and retention of excess fluid.

Taxotere should not be given to patients with low white–blood-cell counts, abnormal liver function, or a history of allergic reactions to Taxotere or any of the ingredients in Taxotere.

Before each Taxotere treatment, all patients treated must receive Dexamethasone. This drug can help reduce the risk of edema and allergic reactions.

Treatment-related acute myeloid leukemia ( AML ) has occurred in patients given anthracyclines and/or Cyclophosphamide, including use with Taxotere in adjuvant therapy for breast cancer.

Because of the potential risk of fetal harm, pregnant women should not receive Taxotere. Women of childbearing potential should avoid becoming pregnant during treatment with Taxotere.

Breast cancer is the most frequently diagnosed cancer in women. It is the second-leading cause of cancer death in women after lung cancer, and since 1990 is increasing predominantly in women 50 and over. It is the first cancer mortality reason in women of 40 to 59 years old.

More than one million new cases of breast cancer are reported worldwide annually and more than 400,000 women die each year from the disease.
The risk of a woman developing breast cancer during her lifetime is approximately 13 percent ( about one in seven of all women in the United States ).
In the European Union, more than 191,000 new cases are diagnosed each year and more than 60,000 women will die.
In the United States, breast cancer will represents this year more than 215,000 new cases and 40,000 will die.

Source:

1) Journal of Clinical Oncology, 2005

2) Sanofi-Aventis, 2005


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