PDF
ePub
Citation
Print
Abstract
Adjuvant chemotherapy plays an important role in improving disease free and overall survival in women with high-risk early stage breast cancer. While more than seventy thousand women have enrolled in taxane-based adjuvant chemotherapy studies, interim and final results are available from several of these randomized phase III adjuvant studies. In this review, we will summarize the design and outcomes from the reported trials, and draw conclusions about the role adjuvant taxanes now play in the standard management of operable breast cancer. In aggregate, these studies show that adjuvant taxanes can improve important clinical outcomes beyond those achieved with anthracycline-based chemotherapy, without imparting prohibitive acute or chronic toxicities. Important questions are being addressed in ongoing adjuvant trials, including comparisons of combination to sequential therapy, direct comparisons between paclitaxel and docetaxel, and how to safely integrate targeted therapies into these highly active adjuvant regimens.
References
1. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003. 21:3357–3365.
2. Senn HJ, Thurlimann B, Goldhirsch A, Wood WC, Gelber RD, Coates AS. Comments on the St. Gallen Consensus 2003 on the Primary Therapy of Early Breast Cancer. Breast. 2003. 12:569–582.
3. National Institutes of Health Consensus Development Conference statement: adjuvant therapy for breast cancer, November 1-3, 2000. J Natl Cancer Inst Monogr. 2001. 30:5–15.
4. Chan S, Friedrichs K, Noel D, Pinter T, Van Belle S, Vorobiof D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999. 17:2341–2354.
5. Jones S, Erban J, Overmoyer B, Budd GT, Hutchins XL, Lower E, et al. Randomized trial comparing docetaxel and paclitaxel in patients with metastatic breast cancer. Breast Cancer Research and Treatment. 2003. 82:Suplement 1. abstract #10.
6. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003. 21:976–983.
7. Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, et al. Sequencing of Tamoxifen and Radiotherapy After Breast-Conserving Surgery in Early-Stage Breast Cancer. J Clin Oncol. 2005. 23:24–29.
8. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2001. 19:602–611.
9. Roche H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Kerbrat P, et al. 6 cycles of FEC 100 vs 3 FEC 100 followed by 3 cycles of docetaxel for node-positive breast cancer patients: analysis at 5 years of the adjuvant PACS -1 trial. Breast Cancer Res and Treat. 2004. 88:Supplement 1. S16. abstract #27.
10. Albain KS, Barlow W, O'Malley F, Siziopikou K, Yeh I-T, Ravdin P, et al. Concurrent (CAFT) versus sequential (CAF-T) chemohormonal therapy (cyclophosphamide, doxorubicin, 5-fluorouracil, tamoxifen) versus T alone for post-menopausal , node-positive, estrogen (ER) and/or progesterone (PgR) receptor-positive breast cancer: mature outcomes and new biologic correlates on phase III intergroup trial 0100 (SWOG-8814). Breast Cancer Res and Treat. 2004. 88:Supplement 1. S16. abstract #37.
11. Muss HB. Adjuvant therapy for older women with breast cancer. Breast. 2003. 12:550–557.
12. Muss HB, Woolf SH, Berry DA, Weiss RB, Budman DR, Wood WC, et al. Older women with node positive (N+) breast cancer (BC) get similar benefits from adjuvant chemotherapy (Adj) as younger patients (pts): The Cancer and Leukemia Group B (CALGB) experience. Proc Am Soc Clin Oncol. 2003. 22:4. abstract #11.
13. Martin M, R-L A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munarriz B, et al. Multicenter, randomized phase III study of adjuvant chemotherapy for node positive breast cancer comparing 6 cycles of FE90C followed by 8 weekly paclitaxel administrations:interim efficacy analysis of GEICAM 9906 Trial. 2005. In : San Antonio Breast Cancer Symposium 2005; San Antonio:
14. Bear HD, Anderson S, Smith RE, Robidoux A, Kahlenbert MS, Margolese RG, et al. A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast : results of NSABP B-27. Breast Cancer Res and Treat. 2004. 88:Supplement 1. S16. Abstract #26.
15. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006. 24:2019–2027.
16. Braakhuis BJ, Hill BT, Dietel M, Kelland LR, Aapro MS, Zoli W, et al. In vitro antiproliferative activity of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin against human tumour and normal bone marrow cells. Anticancer Res. 1994. 14:205–208.
17. Riou JF, Petitgenet O, Combeau C, Lavell F. Cellular uptake and efflux of docetaxel and paclitaxel in P388 cell line. Proc Am Soc Clin. 1994. 35:385. abstract #2292.
18. Diaz JF, Andreu JM. Assembly of purified GDP-tubulin into microtubules induced by taxol and taxotere: reversibility, ligand stoichiometry, and competition. Biochemistry. 1993. 32:2747–2755.
19. Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005. 23:5542–5551.
20. Eniu A, Palmieri FM, Perez EA. Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer. Oncologist. 2005. 10:665–685.
21. Sparano JA, W M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, 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. 2005. In : San Antonio Breast Cancer Symposium 2005; San Antonio:
22. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003. 21:1431–1439.
23. Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006. 295:1658–1667.
24. Hudis C, C M, Berry D, Cirrincione C, Gradishar W, Davidson N, Martino S, et al. Five year follow-up of INT C9741: dose dense (DD) chemotherapy (CRx) is safe and effective. 2005. In : San Antonio Breast Cancer Symposium 2005; San Antonio:
25. Jones SE, Savin MA, Asmar L, Holmes FA, O'Shaughnessy JA, Blum JL, et al. Three-year results of a prospective randomized trial of adjuvant chemotherapy for patients with stage I-III operable, invasive breast cancer comparing four courses of doxorubicin/cyclophsphamide to four courses of docetaxel/cyclophosphamide. Proc Am Soc Clin Oncol. 2003. 22:abstract #59.
26. Jones SE, S M, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja SJ, George TK, et al. Final analysis: TC (docetaxel/cyclophosphamide, 4 cycles) has a superior disease-free survival compared to standard AC (doxorubicin/cyclophosphamide) in 1016 women with early stage breast cancer. 2005. In : San Antonio Breast Cancer Symposium 2005; San Antonio:
27. Nabholtz JM, Mackey JR, Smylie M, Paterson A, Noel DR, Al-Tweigeri T, et al. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol. 2001. 19:314–321.
28. Mackey J, Paterson A, Dirix L. Final results of the phase III randomized trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) to FAC as first line chemotherapy for patients with metastatic breast cancer. Proc Am Soc Clin Oncol. 2002. 21:25a. abstract #137.
29. Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003. 21:968–975.
30. Bontenbal M, Braun JJ, Creemers GJ, de Boer AC. Phase III study comparing AT (Doxorubicin, Docetaxel) to FAC (Fluorouracil, Doxorubicin, Cyclophosphamide) as first-line chemotherapy (CT) in patients with metastatic breast cancer (MBC). Proceedings from the European Conference on Clinical Oncology 2003. abstract #671.
31. Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, et al. TAC improves disease free survival and overall survival over FAC in node positive early breast cancer patients, BCIRG 001: 55 months follow-up. Breast Cancer Research and Treatment. 2003. 82:Supplement 1. abstract #43.
32. Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla J, Weaver C, et al. Docetaxel-based regimen (TAC) improves DFS and OS over FAC in node positive early breast cancer patients: Efficacy, safety and quality of life at 55 month follow-up. In : Proc European Breast Cancer Conference 2004; abstract #50.
33. Berry DA, Cirrincione C, Henderson IC, Citron ML, DR B, Goldstein LJ, et al. Effects of improvements in chemotherapy on disease-free and overall survival of estrogen-receptor negative, node-positive breast cancer: 20-year experience of the CALGB & U.S. Breast Intergroup. Breast Cancer Res. 2200. 88:Supplement 1. abstract #29.
XML Download