Abstract
The discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided IC50 concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose of IC50 concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.
Similar content being viewed by others
References
Burkhart, C. A., Berman, J. W., Swindell, C. S., and Horwitz, S. B., Relationship between the structure of taxol and other taxanes on induction of tumor necrosis factor-a gene expression and cytotoxicity.Cancer Res., 54, 5779–5782 (1994).
Burstein, H. J., Manola, J., Younger, J., Parker, L. M., Bunnell, C. A., Scheib R., Matulonis, U. A., Garber, J. E., Clarke, K. D., Shulman, L. N., and Winer, E. P. Docetaxel administered on a weekly basis for metastatic breast cancer.J. Clin. Oncol., 18, 1212–1219 (2000).
Carlson, R. W., Quality of life issues in the treatment of metastatic breast cancer.Oncology, 12, 27–31 (1998).
Carmichael, J., Jones, A., and Hutchinson, T., A phase II trial of epirubicin plus paclitaxel in metastatic breast cancer.Semin. Oncol., 24, 44–47 (1997).
Chang, A. Y., Boros, L., Asbury, R., Hui, L., and Rubins, J., Dose-escalation study of weekly 1-hour paclitaxel administration in patients with refractory cancer.Semin. Oncol., 24, 17–71 (1997).
Cortes, J. E. and Pazdur R., Docetaxel.J. Clin. Oncol., 13, 2643–2655 (1995).
Esteva, F. J., Valero, V., Pusztai, L., Boehnke, L.-M., Buzdar, A. U., and Hortobagyi, G. N., Chemotherapy of Metastatic Breast Cancer: What to Expect in 2001 and Beyond. The Oncologist, 6, 133–146 (2001).
Greenberg, P. A., Hortobagyi, G. N., Smith, T. L., Ziegler, L. D., Frye, D. K., and Buzdar, A. U., Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer.J. Clin. Oncol., 14, 2197–2205 (1996).
Hainsworth, J. D., Burris, H. A., Erland, J. B., Thomas, M., and Greco, F. A., Phase I trial of docetaxel administered by weekly infusion in patients with advanced refractory cancer.J. Clin. Oncol., 16, 2164–2168 (1998).
Hainsworth, J. D., Burris, H. A., and Greco, F. A., Weekly administration of docetaxel (Taxotere): summary of clinical data.Semin. Oncol., 26, 19–24 (1999).
Hansen, M. B., Nielsen, S. E., and Berg, K., Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill.J. Immunol. Methods, 119, 203–210 (1989).
Jassem, J., Pienkowski, T., Pluzanska, A., Jelic, S., Gorbunova, V., Mrsic, Z.-K., Berzins, J., Nagykalnai, T., Wigler, N., Renard, J., Munier, S., and Weil, C., Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial.J. Clin. Oncol., 19, 1707–1715 (2001).
Klaassen, U., Wilke, H., Strumberg, D., Eberhardt, W., Korn, M., and Seeber, S., Phase I study with a weekly 1 h infusion of paclitaxel in heavily pretreated patients with metastatic breast and ovarian cancer.Eur. J. Cancer, 32, 547–549 (1996).
Lembersky, B. C., Anderson, S., Smith, R., Brown, A., Nesbitt, L., Aikin, J., Fehrenbacher, L., Jochimsen, P., Thirlwell, M. P., and Mamounas, E.P., Phase II trial of doxorubicin and docetaxel for locally advanced and metastatic breast cancer: preliminary results from NSABP BP-57.Proc. Am. Soc. Clin. Oncol., 19, 403 (2000).
Mullins, D. W., Walker, T. M., Burger, C. J. and Elgert, K. D., Taxol-mediated changes in fibrosarcoma-induced immune cell function: modulation of antitumor activities.Cancer. Immunol. Immunother., 45, 20–28 (1997).
Nabholtz, J. M., Docetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer.Semin. Oncol., 26, 7–13 (1999).
Nabholtz, J. M., Tonkin, K., Smylie, M., Au, H. J., Lindsay, M. A., and Mackey, J., Chemotherapy of breast cancer: are the taxanes going to change the natural history of breast cancer?Exp. Opin. Pharmacother., 1, 187–206 (2000).
Paridaens, R., Biganzoli, L., Bruning, P., Klijn, J. G., Gamucci, T., Houston, S., Coleman, R., Schachter, J., Vreckem, A., Sylvester, R., Awada, A., Wildiers, J., and Piccart, M., Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer randomized study with cross-over.J. Clin. Oncol., 18, 724–733 (2000).
Pazdur, R., Kudelka, A.P., Kavanagh, J.J., Cohen, P.R., and Raber, M.N., The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere).Cancer. Treat. Rev., 19, 351–386 (1993).
Perez, E.A., Current management of metastatic breast cancer.Semin. Oncol., 26, 1–10 (1999).
Rowinsky, E. K., The taxanes: dosing and scheduling considerations. Oncology, 11, 7–19 (1997).
Seidman, A. D., Hudis, C. A., Albanel, J., Tong, W., Tepler, I., Currie, V., Moynahan, M. E., Theodoulou, M., Gollub, M., Baselga, J., and Norton, L., Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer.J. Clin. Oncol. 16, 3353–3361 (1998).
Stemmler, H. J., Gutschow, K., Sommer, H., Malekmohammadi, M., Kentenich, C. H., Forstpointner, R., Geuenich, S., Bischoff, J., Hiddemann, W., and Heinemann, V., Weekly docetaxel (Taxotereo) in patients with metastatic breast cancer.Ann. Oncol., 12, 1393–1398 (2001).
Valero, V., Docetaxel as single-agent therapy in metastatic breast cancer: clinical efficacy.Semin. Oncol., 24, 13–18 (1997).
Von Hoff, D. D., The taxoids: same roots, different drugs. Semin. Oncol., 24, 3–13 (1997).
Warburton, S., and James, R., Haemocytometer cell counts and viability studies.In: Doyle, A., Grifits, J. B., and Newell, D. G. (eds.), Cell and tissue culture laboratory procedures, Chichester, John Wiley, pp. 411–415 (1994).
White, C. M., Martin, B. K., Lee, L. R., Haskill, J. S., and Ting, J.P., Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells. Cancer.Immunol. Immunother., 46, 104–112 (1998).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sanli, U.A., Uslu, R., Karabulut, B. et al. Which dosing scheme is suitable for the taxanes? anin vitro model. Arch Pharm Res 25, 550–555 (2002). https://doi.org/10.1007/BF02976617
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976617