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

The North American Breast Cancer Intergroup Trial E1199 is the first head to head trial comparing paclitaxel to docetaxel in the adjuvant treatment of patients with axillary node-positive or high-risk node-negative breast cancer. It follows research highlighting the additional benefits of taxane therapy compared to the standard anthracycline-based adjuvant chemotherapy regimes for women with breast cancer. Furthermore, it has widespread therapeutic implications given current interest regarding adjuvant therapies for the treatment of breast cancer when it is detected at an early stage. Determination of the ideal adjuvant regimen based on the type and stage of breast cancer will promote survival and reduce recurrence of disease. Although results of the phase III clinical trial did not show any significant differences in survival between paclitaxel and docetaxel groups at end-point, paclitaxel was found to be superior in terms of lower toxicity. This has important implications for practitioners prescribing such medications.

Breast cancer is currently the most common cancer in women who do not smoke and is associated with significant morbidity and mortality. Due to advances in screening and evaluation of any breast lump with the triple assessment, the majority of these cases are detected at an early stage, when various treatment options are still viable. Thus, in recent years, research has focussed on the use of adjuvant therapies such as radiotherapy, chemotherapy and endocrine therapy in the treatment of women with breast cancer, to prolong survival and prevent recurrence of disease. With regard to the current study, taxanes have emerged as a beneficial treatment in addition to standard anthracycline-based adjuvant chemotherapy regimes. Taxanes inhibit mitosis by stabilising microtubules, thus preventing further division and advancement of breast carcinoma. Researchers at the North American Breast Cancer Intergroup conducted 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 (tumor at least 2 cm) node-negative breast cancer, from October 1999 to January 2002. Patients were randomised into four treatment groups of 1) paclitaxel 175 mg/m2 every 3 weeks, 2) paclitaxel 80 mg/m2 weekly, 3) docetaxel 100 mg/m2 every 3 weeks or (4) docetaxel 35 mg/m2 weekly.¹ All patients received doxorubicin plus cyclophoshamide (AC) followed by four cycles of the above regimens. Those with estrogen or progesterone positive cancer also received additional adjuvant hormonal therapies. The primary outcomes were examined in terms of disease free survival comparing the individual drugs and the appropriate schedules (3 weekly versus weekly treatment). 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 several years of follow up. Moreover, there were no significant differences between dosing regime schedules. However, researchers did prove some positive findings. In those with oestrogen-receptor negative cancer, weekly paclitaxel may promote survival more than the three-weekly regimes. In addition, researchers identified potential problems with docetaxel treatment. Patients in the weekly docetaxel group had the lowest final percentage receiving all the doses, thus indicating issues with the feasibility and convenience of this regime. Furthermore, those in the three-weekly docetaxel group had significantly higher rates of myelotoxicity with 16% suffering febrile neutropenia compared to one percent or less, in all other groups.² Researchers thus tended towards weekly paclitaxel as the preferred treatment. This study provides new evidence of the benefits of including taxanes in the adjuvant treatment of those with stage II breast cancer. It has important implications for both practitioners and patients, highlighting paclitaxel as the most favoured treatment. This drug showed potential improved survival with less nasty side effects of bone marrow suppression compared to other drugs. However, this study failed to show significant results in several categories and did not consider the widely used AC paclitaxel every-2-weeks; “dose-dense” schedule.² Thus additional research is required to determine the most beneficial adjuvant therapy schedule with particular emphasis on considering patient factors and biological subtypes of cancer that may influence outcome. In particular, the preferred adjuvant treatment for those with oestrogen-receptor positive breast cancer was not evident from this current research. 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).