Evolution of Taxanes in the Treatment of Metastatic Breast Cancer

Sandra Binder

metastasis, breast cancer, breast cancer treatment
CJON 2013, 17(1), 9-14. DOI: 10.1188/13.CJON.S1.9-14

Taxanes have become effective therapies for patients with metastatic breast cancer (MBC); however, understanding the differences among them is important. Each of the taxanes currently approved for treating MBC has a unique formulation, which translates to differences in toxicity profiles and administration considerations. In this article, the rationale for the development of the taxanes paclitaxel, docetaxel, and nab-paclitaxel is reviewed from a historical perspective. The mechanisms of action, formulations, and indications of taxanes also are discussed. The impact of their formulations on clinical practice and patient care, particularly solvent-based versus novel solvent-free formulations, will be reviewed from the nursing perspective.

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    Adams, J.D., Flora, K.P., Goldspeil, B.R., Wilson, J.W., & Arbuck, S.G.I. (1993). Taxol: A history of pharmaceutical development and current pharmaceutical concerns. Journal of the National Cancer Institute. Monographs, 15, 141-147.
    Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular biology of the cell (4th ed.). Retrieved from
    American Society of Health-System Pharmacists. (2013). Drug shortage bulletin: Paclitaxel injection. Retrieved from
    Authier, N., Gillet, J.P., Fialip, J., Eschalier, A., & Coudore, F. (2000). Description of a short-term Taxol-induced nociceptive neuropathy in rats. Brain Research, 887, 239-249. doi:10.1016/S0006-8993(00)02910-3
    Bettelheim, F.A., Brown, W.H., Campbell, M.K., & Farrell, S.O. (2010). Introduction to organic and biochemistry (7th ed.). Belmont, CA: Brooks/Cole, Cengage Learning.
    Bristol-Myers Squibb. (2011). Taxol® (paclitaxel) [Prescribing information]. Retrieved from
    Celgene Corporation. (2012). Abraxane® (nab-paclitaxel) [Prescribing information]. Retrieved from
    Coors, E.A., Seybold, H., Merk, H.F., & Mahler, V. (2005). Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Annals of Allergy, Asthma, and Immunology, 95, 593-599. doi:10.1016/S1081-1206(10)61024-1
    Cortazar, P., Justice, R., Johnson, J., Sridhara, R., Keegan, P., & Pazdur, R. (2012). U.S. Food and Drug Administration approval overview in MBC. Journal of Clinical Oncology, 30, 1705-1711. doi:10.1200/JCO.2011.39.2613
    Cortes, J., & Saura, C. (2010). Nanoparticle albumin-bound (nab)-paclitaxel: Improving efficacy and tolerability by targeted drug delivery in MBC. European Journal of Cancer Supplements, 8, 10. doi:10.1016/S1359-6349(10)70002-1
    de Groen, P.C., Aksamit, A.J., Rakela, J., Forbes, G.S., & Krom, R.A. (1987). Central nervous system toxicity after liver transplantation. The role of cyclosporine and cholesterol. New England Journal of Medicine, 317, 861-866. doi:10.1056/NEJM198710013171404
    Desai, N., Trieu, V., Yao, Z., Louie, L., Ci, S., Yang, A., … Soon-Shiong, P. (2006). Increased antitumor activity, intratumoral paclitaxel concentrations, and endothelial cell transport of Cremophor-free, albumin-bound paclitaxel, ABI-007, compared with Cremophor-based paclitaxel. Clinical Cancer Research, 12, 1317-1324. doi:10.1158/1078-0432.CCR-05-1634
    Force, R.W., Pugmire, B.A., & Culbertson, V.L. (2010). Comparing medical cost of care for patients with MBC receiving taxane therapy: Claims analysis. American Health and Drug Benefits, 3, 276-284.
    Gardner, E.R., Dahut, W.L., Scripture, C.D., Jones, J., Aragon-Ching, J.B., Desai, N., & Figg, W.D. (2008). Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clinical Cancer Research, 14, 4200-4205. doi:10.1158/1078-0432.CCR-07-4592
    Gelderblom, H., Mross, K., ten Tije, A. J., Behringer, D., Mielke, S., van Zomeren, D. M., … Sparreboom, A. (2002). Comparative pharmacokinetics of unbound paclitaxel during 1- and 3-hour infusions. Journal of Clinical Oncology, 20, 574-581.
    Gianni, L., Kearns, C.M., Giani, A., Capri, G., Vigano, L., Locatelli, A., … Egorin, M.J. (1995). Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. Journal of Clinical Oncology, 13, 180-190.
    Gradishar, W.J., Krasnojon, D., Cheporov, S.V., Makhson, A.N., Manikhas, G.M., Clawson, A., & Iglesias, J. (2012). A phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: Final analysis of overall survival. Clinical Breast Cancer, 12, 313-321. doi:10.1016/j.clbc.2012.05.001
    Gradishar, W.J., Tjulandin, S., Davidson, N., Shaw, H., Desai, N., Bhar, P., … O'Shaughnessy, J. (2005). Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Journal of Clinical Oncology, 23, 7794-7803. doi:10.1200/JCO.2005.04.937
    Howlader, N., Noone, A.M., Krapcho, M., Neyman, N., Aminou, R., Altekruse, S.F., … Cronin, K.A. (Eds.). (2012). SEER cancer statistics review, 1975-2009. Retrieved from
    Huttel, M.S., Olesen, A.S., & Stoffersen, E. (1980). Complement-mediated reactions to diazepam with Cremophor as solvent (steroid MR). British Journal of Anasthesiology, 52, 77-79.
    John, T.A., Vogel, S.M., Tiruppathi, C., Malik, A.B., & Minshall, R.D. (2003). Quantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. American Journal of Physiology: Lung Cellular and Molecular Physiology, 284, L187-L196. doi:10.1152/ajplung.00152.2002
    Jones, S.E., Erban, J., Overmoyer, B., Budd, G.T., Hutchins, L., Lower, E., & Ravdin, P.M. (2005). Randomized phase III study of docetaxel compared with paclitaxel in MBC. Journal of Clinical Oncology, 23, 5542-5551. doi:10.1200/JCO.2005.02.027
    Jordan, M.A., & Wilson, L. (2004) Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4, 253-265.
    Kearns, C.M. (1997). Pharmacokinetics of the taxanes. Pharmacotherapy, 17(5, Pt. 2), 105S-109S.
    Kingston, D.G. (2007). The shape of things to come: Structural and synthetic studies of taxol and related compounds. Phytochemistry, 68, 1844-1854. doi:10.1016/j.phytochem.2006.11.009
    Kongshaug, M., Cheng, L.S., Moan, J., & Rimington, C. (1991). Intreraction of Cremophor-EL with human plasma. International Journal of Biochemistry, 23, 473-478.
    Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., & Darnell, J. (2000). Microtubule dynamics and associated proteins. Retrieved from
    Maeda, H., Wu, J., Sawa, T., Matsumura, Y., & Hori, K. (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. Journal of Controlled Release, 65, 271-284. doi:10.1016/S0168-3659(99)00248-5
    Malik, S., Cusido, R.M., Mirjalili, M.H., Moyano, E., Palazon, J., & Bonfill, M. (2011). Production of the anticancer drug Taxol in Taxus baccata suspension cultures: A review. Process Biochemistry, 46, 23-34. doi:10.1016/j.procbio.2010.09.004
    Matsumura, Y., & Maeda, H. (1986). A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent Smancs. Cancer Research, 46, 6387-6392.
    McLeod, H.L., Kearns, C.M., Kuhn, J.G., & Bruno, R. (1998). Evaluation of the linearity of docetaxel pharmacokinetics. Cancer Chemotherapy and Pharmacology, 42, 155-159.
    Nabholtz, J.M., Gelmon, K., Bontenbal, M., Spielmann, M., Catimel, G., Conte, P., … Winograd, B. (1996). Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. Journal of Clinical Oncology, 14, 1858-1867.
    Nabholtz, J.M., Senn, H.J., Bezwoda, W.R., Melnychuk, D., Deschenes, L., Douma, J., … Aapro, M. (1999). Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with MBC progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. Journal of Clinical Oncology, 17, 1413-1424.
    Prajapati, K.D., Sharma, S.S., & Roy, N. (2011). Current perspectives on potential role of albumin in neuroprotection. Reviews in the Neurosciences, 22, 355-363. doi:10.1515/RNS.2011.028
    Rowinsky, E.K., & Donehower, R.C. (1995). Paclitaxel (Taxol®). New England Journal of Medicine, 332, 1004-1014.
    sanofi-aventis. (2010). Taxotere® (docetaxel) [Prescribing information]. Retrieved from
    Schiff, P.B., Fant, J., & Horwitz, S.B. (1979). Promotion of microtubule assembly in vitro by Taxol. Nature, 277, 665-667.
    Seidman, A.D., Berry, D., Cirrincione, C., Harris, L., Muss, H., Marcom, P.K., … Hudis, C. (2008). Randomized phase III trial of weekly compared with every-three-weeks paclitaxel for MBC, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: Final results of Cancer and Leukemia Group B protocol 9840. Journal of Clinical Oncology, 26, 1642-1649. doi:10.1200/JCO.2007.11.6699
    Simionescu, M., Gafencu, A., & Antohe, F. (2002). Transcytosis of plasma macromolecules in endothelial cells: A cell biological survey. Microscopy Research and Technique, 57, 269-288.
    Sparano, J.A. (2000). Taxanes for breast cancer: An evidence-based review of randomized phase II and phase III trials. Clinical Breast Cancer, 1, 32-40.
    Sparano, J.A., Wang, M., Martino, S., Jones, V., Perez, E.A., Saphner, T., & Davidson, N.E. (2008). Weekly paclitaxel in the adjuvant treatment of breast cancer. New England Journal of Medicine, 358, 1663-1671. doi:10.1056/NEJMoa0707056
    Sparreboom, A., van Zuylen, L., Brouwer, E., Loos, W.J., de Bruijn, P., Gelderblom, H., & Verweij, J. (1999). Cremophor EL-mediated alteration of paclitaxel distribution in human blood: Clinical pharmacokinetic implications. Cancer Research, 59, 1454-1457.
    Stehle, G., Sinn, H., Wunder, A., Schrenk, H.H., Stewart, J.C.M., Gartung, G., … Heene, D.L. (1997). Plasma protein (albumin) catabolism by the tumor itself—Implications for tumor metabolism and the genesis of cachexia. Critical Reviews in Oncology Hematology, 26, 77-100.
    ten Tije, A.J., Verweij, J., Loos, W.J., & Sparreboom, A. (2003). Pharmacological effects of formulation vehicles: Implications for cancer chemotherapy. Clinical Pharmacokinetics, 42, 665-685.
    Watkins, J., Ward, A.M., & Appleyard, T.N. (1997). Adverse reactions in intravenous anasthetic induction agents. BMJ, 2, 1084-1085.
    Wilson, L., Creswell, K.M., & Chin, D. (1975). Mechanism of action of vinblastine. Binding of [acetyl-3H]-vinblastine to embryonic chick brain tubulin and tubulin from sea urchin sperm tail outer doublet microtubules. Biochemistry, 14, 5586-5592.
    Windebank, A.J., Blexrud, M.D., & de Groen, P.C. (1994). Potential neurotoxicity of the solvent vehicle for cyclosporine. Journal of Pharmacology and Experimental Therapeutics, 268, 1051-1056.
    Woodburn, K., & Kessel, D. (1994). The alteration of plasma-lipoproteins by Cremophor EL. Journal of Photochemistry and Photobiology B, 22, 197-201.