Adjuvant Taxanes in the Treatment of Breast Cancer: No Longer at the Tip of the Iceberg
Department of Medicine, Breast Cancer Medicine Service Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Clinical Breast Cancer
(Impact Factor: 2.11).
05/2006; 7(1):51-8. DOI: 10.3816/CBC.2006.n.013
Breast cancer is one of the leading causes of cancer-related mortality, and a cure is desperately needed. Adjuvant chemotherapy with anthracycline-based regimens has been proven to decrease the risk of relapse and cancer-related mortality in women with early-stage breast cancer. The taxanes (paclitaxel and docetaxel) have been incorporated into several adjuvant chemotherapy regimens in recent studies. Some of these trials are now mature and have demonstrated a definitive benefit with the use of taxanes. Thus, taxanes should be incorporated into the adjuvant treatment of breast cancer. To date, the available data do not allow one to select a single best taxane, schedule, or overall regimen.
Available from: Bernard Asselain
- "Over the last three decades, adjuvant systemic chemotherapy for early breast cancer has delivered steadily improving outcomes, as a result of the introduction of new cytotoxic agents such as anthracyclines and taxanes, the optimisation of standard regimens administration, and more recently, better patient selection using elaborate prognostic algorithms (Dang and Hudis, 2006; Levine and Whelan, 2006). Polychemotherapy regimens based on an anthracycline and taxane backbone have emerged as the international standard in high-risk breast cancer including node positive (pN þ ) cases (Goldhirsch et al, 2009). "
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ABSTRACT: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy.
Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis.
In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%).
Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.
Available from: Sebastien Roger
- "Taxol and its derivatives, such as docetaxel, are used in breast cancer chemotherapy . The classically accepted mechanism of action is the stabilization of the mitotic spindle, leading to an inhibition of cell proliferation. "
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ABSTRACT: Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (Na(V)) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting Na(V) activity with tetrodotoxin is responsible for an approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study, we focused on the effect of a single, 2-h application of 10 nM taxol on the two cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect on proliferation after 7 days and on migration in any cell line. However it led to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no additive effect when taxol and tetrodotoxin were simultaneously applied. Na(V) activity, as assessed by patch-clamp, indicates that it was changed by taxol pre-treatment. We conclude that taxol can exert anti-tumoral activities, in cells expressing Na(V), at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels.
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