Pharmacologic, Pre-clinical and Clinical Investigations of the Cisplatin/Taxol Combination

  • Eric K. Rowinsky
  • William P. McGuire
  • Dennis A. Noe
  • Mark R. Gilbert
  • Martin J. Citardi
  • Ross C. Donehower


Taxol, the prototype of a novel class of antimicrotubule agents that is derived from the bark of the Pacific yew Taxus brevifolia, induces excessive polymerization of tubulin and impairs the dynamic equilibrium between tubulin and microtubules interfering with normal cellular functions.1–4 Taxol (Figure 1) is the first compound with a taxene ring that has been demonstrated to possess antineoplastic activity,5 and it has become one of the most important lead anticancer agents to recently emerge from the screening of natural products.


Absolute Neutrophil Count Gynecologic Oncology Group Lower Dose Level L1210 Leukemia Cell Sequence Permutation 
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  1. 1.
    E. K. Rowinsky, L. A. Cazenave, and R.C. Donehower, Taxol: a novel investigational antineoplastic agent, J. Natl. Can. Inst. 82:1247 (1247).CrossRefGoogle Scholar
  2. 2.
    P. B. Schiff, J. Fant, and S. B. Horwitz, Promotion of microtubule assembly in vitro by taxol, Nature 22:665 (1979).CrossRefGoogle Scholar
  3. 3.
    P. B. Schiff, and S. B. Horwitz, Taxol stabilizes microtubules in mouse fibroblast cells, Proc. Natl. Acad. Sci. U.S.A. 77:1561 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    J. J. Manfredi, and S. B. Horwitz, Taxol: an antimitotic agent with a new mechanism of action. Pharmac. Ther. 25:83 (1984).CrossRefGoogle Scholar
  5. 5.
    M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggan, and A. T. McPhail, Plant antitumor agents VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from taxus brevifolia. Am. Chem. Soc. 93:2325 (1971).CrossRefGoogle Scholar
  6. 6.
    National Cancer Institute Clinical Brochure: Taxol (NSC 125973). Division of Cancer Treatment, NCI, Bethesda, MD, pp. 6-12, (1983).Google Scholar
  7. 7.
    R. C. Donehower, E. K. Rowinsky, L. B. Grochow LB, S. M. Longnecker, and D. S. Ettinger, Phase I trial of taxol in patients with advanced malignancies, Cancer Treat. Rep. 71:1171 (1987).PubMedGoogle Scholar
  8. 8.
    T. Ohnuma, A. S. Zimet, V. A. Coffey, J. F. Holland, and E. M. Greenspan, Phase I study of taxol in a 24-hr infusion schedule, Proc. Am. Assoc. Can. Res. 26:662 (1985).Google Scholar
  9. 9.
    M. G. Kris, J. P. O’Connell, R. J. Gralla, M. S. Wertheim, R. M. Parente, P. B. Schiff, and C. W. Young, Phase I trial of taxol given as a 3-hour infusion every 21 days. Cancer Treat. Rep. 70:605 (1986).PubMedGoogle Scholar
  10. 10.
    S. S. Legha, D. M. Tenney, and I. R. Krakoff, Phase I study of taxol using a 5-day intermittent schedule, J. Clin. Oncol. 4:762 (1986).PubMedGoogle Scholar
  11. 11.
    E. K. Rowinsky, P. J. Burke, J. E. Karp, R. W. Tucker, D. S. Ettinger, and R. C. Donehower, Phase I study of taxol in refractory adult acute leukemia, Cancer Res. 49:4640 (1989).PubMedGoogle Scholar
  12. 12.
    J. L. Grem, K. D. Tutsch, K. J. Simon, D. A. Alberti, J. K. Wilson, D. C. Tormey, S. Swaminathan, and D. L. Trump, Phase I study of taxol administered as a short iv infusion daily for 5 days, Cancer Treat, Rep, 71:1179–1184 (1987).Google Scholar
  13. 13.
    P. H. Wiernik, E. L. Schwartz, A. Einzig, J. J. Strauman, R. B. Lipton, and J. P. Dutcher, Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. J. Clin. Oncol. 5:1232 (1987).PubMedGoogle Scholar
  14. 14.
    P. H. Wiernik, E. L. Schwartz, J. J. Strauman, J. P. Dutcher, R. B. Lipton, and E. Paietta, Phase I clinical and pharmacokinetic study of taxol, Cancer Res. 47:2486 (1987).PubMedGoogle Scholar
  15. 15.
    J. Koeller, T. Brown, T. K. Havlin, J. Kuhn, J. Craig, J. Rizzo, J. Philips, and D. Von Hoff, A phase I/pharmacokinetic study of taxol given by a prolonged infusion without premedication, Proc. Am. Soc. Clin. Oncol. 8:82 (1989).Google Scholar
  16. 16.
    S. M. Longnecker, R. C. Donehower, A. E. Cates, T-L Chen, R. B. Brundrett, L. B. Grochow, D. S. Ettinger, and M. C. Colvin, High performance liquid chromatographic assay for taxol (NSC 125973) in human plasma and urine pharmacokinetics in a phase I trial, Cancer Treat. Rep. 71:53 (1986).Google Scholar
  17. 17.
    E. K. Rowinsky, R. C. Donehower, R. J. Jones, and R. W. Tucker, Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res. 48:4093 (1988).PubMedGoogle Scholar
  18. 18.
    A. I. Einzig, E. Gorowski, J. Sasloff, and P. H. Wiernik, Phase II trial or taxol in patients with renal cell carcinoma. Proc. Am. Ass. Can. Res. 29:222 (1988).Google Scholar
  19. 19.
    A. I. Einzig, D. L. Trump DL, J. Sasloff, S. Garl, and K. A. Hanlan, Phase II pilot study of taxol in patients (pts) with malignant melanoma (mm). Proc. Am. Soc. Clin. Oncol. 7:249 (1988).Google Scholar
  20. 20.
    S. S. Legha, S. Ring, N. Papadopoulos, M. Raber, and R. Benjamin, Taxol: A phase II study in patients with metastatic melanoma. Cancer 65:2478 (1990).PubMedCrossRefGoogle Scholar
  21. 21.
    W. P. McGuire, E. K. Rowinsky, N. B. Rosenshein, F. C. Grumbine, D. S. Ettinger, D. K. Armstrong, and R. C. Donehower, Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann. Intern. Med. 111:273 (1989).PubMedCrossRefGoogle Scholar
  22. 22.
    A. I. Einzig, P. Wiernik, J. Sasloff, S. Garl, C. Runowicz, K. A. O’Hanlan, and G. Goldberg, Phase II study of taxol in patients with advanced ovarian cancer. Proc. Am. Assoc. Can. Res. 31:1114 (1989).Google Scholar
  23. 23.
    T. Thigpen, J. Blessing, H. Ball, H. Hummel, and S. Barret, Phase II trial of taxol as second-line therapy for ovarian carcinoma: a gynecologic oncology group study, Proc. Am. Soc. Clin. Oncol. 9:604 (1990).Google Scholar
  24. 24.
    R. Weiss, R. C. Donehower, P. H. Wiernik, T. Ohnuma, R. J. Gralla, D. L. Trump, J. R. Baker, D. A. Van Echo, D. D. Von Hoff, and B. Leyland-Jones, Hypersenstivity reactions from taxol, J. Clin. Oncol. 8:1263 (1990).PubMedGoogle Scholar
  25. 25.
    M. Weiss M, Model-independent assessment of accumulation kinetics based on moments of drug disposition curves. Eur. J. Clin. Pharmacol. 27:355 (1984).PubMedCrossRefGoogle Scholar
  26. 26.
    J. J. DiStefano, Concepts, properties, measurement, and computation of clearance rates of hormones and other substances in biological systems. Ann. Biomed. Eng. 4:302 (1976).CrossRefGoogle Scholar
  27. 27.
    J. Hilton, Deoxyribonucleic acid crosslinking by 4-hydroperoxycyclo-phosphamide in cyclophosphamide-sensitive and-resistant L1210 cells. Biochem. Pharmacol. 33:1867 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Eric K. Rowinsky
    • 1
  • William P. McGuire
    • 1
  • Dennis A. Noe
    • 1
  • Mark R. Gilbert
    • 1
  • Martin J. Citardi
    • 1
  • Ross C. Donehower
    • 1
  1. 1.The Johns Hopkins Oncology CenterBaltimoreUSA

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