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Which dosing scheme is suitable for the taxanes? anin vitro model

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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.

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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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Carlson, R. W., Quality of life issues in the treatment of metastatic breast cancer.Oncology, 12, 27–31 (1998).

    PubMed  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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).

    Google Scholar 

  • Cortes, J. E. and Pazdur R., Docetaxel.J. Clin. Oncol., 13, 2643–2655 (1995).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  Google Scholar 

  • 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).

    Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Nabholtz, J. M., Docetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer.Semin. Oncol., 26, 7–13 (1999).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Perez, E.A., Current management of metastatic breast cancer.Semin. Oncol., 26, 1–10 (1999).

    PubMed  CAS  Google Scholar 

  • Rowinsky, E. K., The taxanes: dosing and scheduling considerations. Oncology, 11, 7–19 (1997).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Valero, V., Docetaxel as single-agent therapy in metastatic breast cancer: clinical efficacy.Semin. Oncol., 24, 13–18 (1997).

    CAS  Google Scholar 

  • Von Hoff, D. D., The taxoids: same roots, different drugs. Semin. Oncol., 24, 3–13 (1997).

    Google Scholar 

  • 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).

    Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

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Correspondence to Erdem Goker.

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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

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