Novel study comparing paclitaxel to docetaxel in the treatment of breast cancer

Breast cancer is the most common cancer in women worldwide so identification of appropriate treatments to prolong survival and prevent recurrence in patients diagnosed early, is of paramount importance. A recent trial by the North American Breast Cancer Intergroup E1199 is the first study to compare two drugs (paclitaxel and docetaxel) of a class of drugs known as taxanes, which inhibit breast cancer cells dividing. These types of drugs are usually used as an add-on therapy after surgery or the use other chemotherapeutic agents (drugs that try to reduce tumours growing, kill cancer cells or stop them from spreading). This study follows other trials that have shown taxanes to be beneficial in prolonging survival. The final results however, did not show any significant differences between paclitaxel and docetaxel in terms of survival, but found docetaxel had more common potentially dangerous side-effects.

Advances in diagnostic techniques means breast cancer is often diagnosed at an early stage where several treatment options are available. Breast cancer often presents as a painless lump which after examination by palpation (feeling), radiology and fine needle aspirate (taking a small sample of cells with a needle) can be determined as breast cancer as opposed to another benign mass. The type and stage of breast cancer can also be determined. Wide-spread screening by mammography also promotes detection of breast cancer at an early stage. The types of adjuvant (add-on) therapies such as chemotherapy, radiotherapy and hormone treatments continues to expand so research is required to determine the most beneficial and safest treatment suited to individual patients. Researchers at the North American Breast Cancer Intergroup considered only one form of therapy, namely the taxanes in the treatment of certain severities of breast cancer. In particular, it is the first head to head trial between paclitaxel and docetaxel comparing the efficacy, safety and appropriate regimes of these drugs.The study included 4988 women with lymph node positive or high-risk node-negative breast cancer, from October 1999 to January 2002. (Lymph node positive or negative refers to whether the cancer has spread to affect the lymph nodes, special glands that help to treat infections.) All patients received 12 weeks of doxorubicin and cyclophosphamide which inhibit replication and kill cancer cells by separate mechanisms. Following this, patients were divided into four groups to receive paclitaxel weekly, paclitaxel 3-weekly, docetaxel weekly or docetaxel 3-weekly at specific doses. They received four cycles of treatment and at end-point were compared in terms of disease free survival (DFS) comparing both the individual drugs to each other and the different dosing regimes. Results of the study were released at San Antonio in December 2005. Neither paclitaxel nor docetaxel was found superior in terms of DFS or overall survival after nearly four years of follow up. Moreover, there were no significant differences between dosing regime schedules. However, researchers did prove some positive findings. There was a trend for weekly paclitaxel to provide better survival than the three weekly regimes. In addition, researchers identified potential problems with docetaxel treatment. The weekly docetaxel group had the lowest percentage of patients receive all their doses, indicating issues with the feasibility and convenience of this regime. Furthermore, those in the three-weekly docetaxel group had significantly higher rates of myelotoxicity. This is a nasty side effect where the drug treatments damage the bone marrow in the body (as this is also rapidly dividing like the cancer cells, so is accidentally targeted). Bone marrow is the soft, pulpy substance found in the central cavity of bones that has important roles in the production of different blood cells. Damage to the bone marrow predisposes patients to bleeding, anaemia and infection. Researchers thus tended towards weekly paclitaxel as the preferred treatment. This study has important applications in the treatment of breast cancer that is detected in a relatively early stage of disease. Currently, paclitaxel is a commonly used and well known drug. Research suggesting it may be superior to other alternatives by possibly increasing survival and lowering side-effects is important information for patients and their practitioners. However, this study only showed modest benefits of paclitaxel relative to docetaxel and the best dosing regimen is not particularly clear. Further research is needed to address some of these areas and to learn which drugs are best for particular patients and types of cancer. It does however; highlight a promising therapy for some patients with breast cancer. Your doctor will determine if paclitaxel is the most appropriate therapy for your individual circumstances.Sources:[1] Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Sledge GW, Wood WC, Davidson NE. ‘Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer: results of North American Breast Cancer Intergroup Trial E1199.’ Breast Cancer Res Treat. 2005; 94(suppl 1). Late-breaking Abstract 48. [2] Burstein HJ. ‘Update on Adjuvant Therapy for Breast Cancer: The Expanding Role of Targeted Therapy and Taxanes.’ Medscape 2006. [3] Perez EA, Peppercorn J. ‘Current strategies for adjuvant treatment of breast cancer. An expert interview with Dr. Edith A Perez.’ Medscape Haematology Oncology. 2006;9(1).