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Clinical Pharmacology and Use of Microtubule-Targeting Agents in Cancer Therapy

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Microtubule Protocols

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 137))

Abstract

The microtubule-targeting agents have made significant contributions to cancer therapy over the past 50 years. The vinca alkaloids and taxanes have been used to treat a broad range of malignancies, including leukemias and lymphomas and many types of solid tumors. The taxanes have been frequently used in the treatment of advanced ovarian, breast, lung, head and neck, and prostate cancer, and they are increasingly being used in early stage disease. This chapter reviews the pharmacology, clinical indications, and toxicities associated with the vinca alkaloids and taxanes.

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References

  1. Noble, R., Beer, C. T., and Cutts, J. H. (1958) Role of change observations in chemotherapy: Vinca rosea. Ann. N.Y. Acad. Sci. 76, 882ā€“894.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  2. Karon, M., Freireich, E. J., and Frei, E. I. (1962) A preliminary report on vincristine sulfate; a new active agent for the treatment of acute leukemia. Pediatrics 30, 791ā€“802.

    Google ScholarĀ 

  3. Costa, G., Hreshchyshyn, M. M., and Holland, J. F. (1962) Initial clinical studies with vincristine. Cancer Chemother. Rep. 24, 39ā€“44.

    CASĀ  PubMedĀ  Google ScholarĀ 

  4. Donoso, J. A., Haskins, K. M., and Himes, R. H. (1979) Effect of microtubule-associated proteins on the interaction of vincristine with microtubules and tubulin. Cancer Res. 39, 1604ā€“1610.

    CASĀ  PubMedĀ  Google ScholarĀ 

  5. George, P., Journey, L. J., and Goldstein, M. N. (1965) Effect of vincristine on the fine structure of HeLa cells during mitosis. J. Natl. Cancer Inst. 35, 355ā€“375.

    CASĀ  PubMedĀ  Google ScholarĀ 

  6. Himes, R. H., Kersey, R. N., Heller-Bettinger, I., and Samson, F. E. (1976) Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res. 36, 3798ā€“3802.

    CASĀ  PubMedĀ  Google ScholarĀ 

  7. Jordan, M. A., Thrower, D., and Wilson, L. (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res. 51, 2212ā€“2222.

    CASĀ  PubMedĀ  Google ScholarĀ 

  8. Owellen, R. J., Hartke, C. A., Dickerson, R. M., and Hains, F. O. (1976) Inhibition of tubulin-microtubule polymerization by drugs of the Vinca alkaloid class. Cancer Res. 36, 1499ā€“1502.

    CASĀ  PubMedĀ  Google ScholarĀ 

  9. Rahmani, R. and Zhou, X. J. (1993) Pharmacokinetics and metabolism of vinca alkaloids. Cancer Surv. 17, 269ā€“281.

    CASĀ  PubMedĀ  Google ScholarĀ 

  10. Owellen, R. J., Root, M. A., and Hains, F. O. (1977) Pharmacokinetics of vindesine and vincristine in humans. Cancer Res. 37, 2603ā€“2607.

    CASĀ  PubMedĀ  Google ScholarĀ 

  11. Sethi, V. S., Jackson, D. V., Jr., White, D. R., et al. (1981) Pharmacokinetics of vincristine sulfate in adult cancer patients. Cancer Res. 41, 3551ā€“3555.

    CASĀ  PubMedĀ  Google ScholarĀ 

  12. Sethi, V. S. and Kimball, J. C. (1981) Pharmacokinetics of vincristine sulfate in children. Cancer Chemother. Pharmacol. 6, 111ā€“115.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  13. Bender, R. A., Castle, M. C., Margileth, D. A., and Oliverio, V. T. (1977) The pharmacokinetics of [3H]-vincristine in man. Clin. Pharmacol. Ther. 22, 430ā€“435.

    CASĀ  PubMedĀ  Google ScholarĀ 

  14. Zhou-Pan, X. R., Seree, E., Zhou, X. J., et al. (1993) Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions. Cancer Res. 53, 5121ā€“5126.

    CASĀ  PubMedĀ  Google ScholarĀ 

  15. Zhou, X. J., Zhou-Pan, X. R., Gauthier, T., Placidi, M., Maurel, P., and Rahmani, R. (1993) Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem. Pharmacol. 45, 853ā€“861.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  16. El Dareer, S. M., White, V. M., Chen, F. P., Mellet, L. B., and Hill, D. L. (1977) Distribution and metabolism of vincristine in mice, rats, dogs, and monkeys. Cancer Treat. Rep. 61, 1269ā€“1277.

    PubMedĀ  Google ScholarĀ 

  17. Jackson, D. V., Jr., Castle, M. C., and Bender, R. A. (1978) Biliary excretion of vincristine. Clin. Pharmacol. Ther. 24, 101ā€“107.

    PubMedĀ  Google ScholarĀ 

  18. Rosenthal, S. and Kaufman, S. (1974) Vincristine neurotoxicity. Ann. Intern. Med. 80, 733ā€“737.

    CASĀ  PubMedĀ  Google ScholarĀ 

  19. Sandler, S. G., Tobin, W., and Henderson, E. S. (1969) Vincristine-induced neuropathy. A clinical study of fifty leukemic patients. Neurology 19, 367ā€“374.

    CASĀ  PubMedĀ  Google ScholarĀ 

  20. Van den Berg, H. W., Desai, Z. R., Wilson, R., Kennedy, G., Bridges, J. M., and Shanks, R. G. (1982) The pharmacokinetics of vincristine in man: reduced drug clearance associated with raised serum alkaline phosphatase and dose-limited elimination. Cancer Chemother. Pharmacol. 8, 215ā€“219.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  21. Owellen, R. J. and Hartke, C. A. (1975) The pharmacokinetics of 4-acetyl tritium vinblastine in two patients. Cancer Res. 35, 975ā€“980.

    CASĀ  PubMedĀ  Google ScholarĀ 

  22. Owellen, R. J., Hartke, C. A., and Hains, F. O. (1977) Pharmacokinetics and metabolism of vinblastine in humans. Cancer Res. 37, 2597ā€“2602.

    CASĀ  PubMedĀ  Google ScholarĀ 

  23. Marquet, P., Lachatre, G., Debord, J., Eichler, B., Bonnaud, F., and Nicot, G. (1992) Pharmacokinetics of vinorelbine in man. Eur. J. Clin. Pharmacol. 42, 545ā€“547.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  24. Leveque, D., Jehl, F., Quoix, E., and Breillout, F. (1992) Clinical pharmacokinetics of vinorelbine alone and combined with cisplatin. J. Clin. Pharmacol. 32, 1096ā€“1098.

    CASĀ  PubMedĀ  Google ScholarĀ 

  25. Bore, P., Rahmani, R., van Cantfort, J., Focan, C., and Cano, J. P. (1989) Pharmacokinetics of a new anticancer drug, navelbine, in patients. Comparative study of radioimmunologic and radioactive determination methods. Cancer Chemother. Pharmacol. 23, 247ā€“251.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  26. Mathe, G. and Reizenstein, P. (1985) Phase I pharmacologic study of a new Vinca alkaloid: navelbine. Cancer Lett. 27, 285ā€“293.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  27. Khayat, D., Rixe, O., Brunet, R., et al. (2004) Pharmacokinetic linearity of i.v. vinorelbine from an intra-patient dose escalation study design. Cancer Chemother. Pharmacol. 54, 193ā€“205.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  28. Gidding, C. E., Kellie, S. J., Kamps, W. A., and de Graaf, S. S. (1999) Vincristine revisited. Crit. Rev. Oncol. Hematol. 29, 267ā€“287.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  29. Rowinsky, E. K. and Donehower, R. C. (1991) The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol. Ther. 52, 35ā€“84.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  30. Lampert, F. and Henze, G. (1997) Acute lymphoblastic leukaemia, in Pediatric Oncology: Clinical Practice and Controversies, (Pinkerton, C. and Plowman, P. N., ed.), Chapman & Hall Medical, London, UK, pp. 258ā€“278.

    Google ScholarĀ 

  31. Patte, C. (1997) Childhood non-Hodgkinā€™s lymphoma, in Pediatric Oncology: Clinical Practice and Controversies, (Pinkerton, C. and Plowman, P. N., ed.), Chapman & Hall Medical, London, UK, pp. 278ā€“291.

    Google ScholarĀ 

  32. Oberlin, O. and McDowell, H. P. (1997) Hodgkinā€™s disease, in Pediatric Oncology: Clinical Practice and Controversies, (Pinkerton, C. and Plowman, P. N., ed.), Chapman & Hall Medical, London, UK, pp. 296ā€“316.

    Google ScholarĀ 

  33. Dā€™Angio, G. J., Evans, A. E., Breslow, N., et al. (1976) The treatment of Wilmsā€™ tumor: Results of the national Wilmsā€™ tumor study. Cancer 38, 633ā€“646.

    ArticleĀ  CASĀ  Google ScholarĀ 

  34. Ninane, J. and Pearson, A. D. J. (1997) Neuroblastoma, in Pediatric Oncology: Clinical Practice and Controversies, (Pinkerton, C. and Plowman, P. N., ed.), Chapman & Hall Medical, London, UK, pp. 443ā€“446.

    Google ScholarĀ 

  35. Wexler, L. and Helman, L. J. (1997) Rhabdomyosarcoma and the undifferentiated sarcomas, in Principles and Practice of Pediatric Oncology, (Pizzo, P. and Poplack, D. G., ed.), Lippincott-Raven, Philadelphia, PA, pp. 799ā€“830.

    Google ScholarĀ 

  36. Horowitz, M., Malawer, M. M., and Woo, S. Y. (1997) Hicks JM Ewingā€™s sarcoma family of tumors: Ewingā€™s neuroectodermal tumors, in Principles and Practice of Pediatric Oncology, (Pizzo, P. and Poplack, D. G., ed.), Lippincott-Raven, Philadelphia, PA, pp. 831ā€“863.

    Google ScholarĀ 

  37. Armitage, J., Mauch, P. M., Harris, N. L., and Bierman, P. (2001) Non-Hodgkinā€™s lymphomas, in Cancer: Principles and Practice of Oncology, (DeVita, Jr, V. T., Hellman, S., and Rosenberg, S. A., ed.), Lippincott Williams & Wilkins, Philadelphia, PA, pp. 2256ā€“2315.

    Google ScholarĀ 

  38. Diehl, V., Mauch, P. M., and Harris, N. L. (2001) Hodgkinā€™s Disease, in Cancer: Principles and Practice of Oncology, (DeVita, Jr, V. T., Hellman, S., and Rosenberg, S. A., ed.), Lippincott Williams & Wilkins, Philadelphia, PA, pp. 2339ā€“2388.

    Google ScholarĀ 

  39. DeVita, V., Serpick, A. A., and Carbone, P. P. (1970) Combination chemotherapy in the treatment of advanced Hodgkinā€™s disease. Ann. Intern. Med. 73, 891ā€“895.

    Google ScholarĀ 

  40. Longo, D. L., Young, R. C., Wesley, M., et al. (1986) Twenty years of MOPP therapy for Hodgkinā€™s disease. J. Clin. Oncol. 4, 1295ā€“1306.

    CASĀ  PubMedĀ  Google ScholarĀ 

  41. Horning, S. J., Hoppe, R. T., Breslin, S., Bartlett, N. L., Brown, B. W., and Rosenberg, S. A. (2002) Stanford V and radiotherapy for locally extensive and advanced Hodgkinā€™s disease: mature results of a prospective clinical trial. J. Clin. Oncol. 20, 630ā€“637.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  42. Kantarjian, H. M., Oā€™Brien, S., Smith, T. L., et al. (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J. Clin. Oncol. 18, 547ā€“561.

    CASĀ  PubMedĀ  Google ScholarĀ 

  43. Samson, D., Gaminara, E., Newland, A., et al. (1989) Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet 2, 882ā€“885.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  44. Kaplan, L., Abrams, D., and Volberding, P. (1986) Treatment of Kaposiā€™s sarcoma in acquired immunodeficiency syndrome with an alternating vincristine-vinblastine regimen. Cancer Treat. Rep. 70, 1121ā€“1122.

    CASĀ  PubMedĀ  Google ScholarĀ 

  45. Gill, P., Rarick, M., Bernstein-Singer, M., et al. (1990) Treatment of advanced Kaposiā€™s sarcoma using a combination of bleomycin and vincristine. Am. J. Clin. Oncol. 13, 315ā€“319.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  46. Livingston, R. and Carter, S. K. (1970) Single Agents in Cancer Chemotherapy, IFI/Plenum, New York.

    Google ScholarĀ 

  47. Santoro, A. and Bonadonna, G. (1979) Prolonged disease-free survival in MOPP-resistant Hodgkinā€™s disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother. Pharmacol. 2, 101ā€“105.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  48. Papa, G., Mandelli, F., Anselmo, A. P., et al. (1982) Treatment of MOPP-resistant Hodgkinā€™s disease with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Eur. J. Cancer Clin. Oncol. 18, 803ā€“806.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  49. Carbone, P. P., Spurr, C., Schneiderman, M., Scotto, J., Holland, J. F., and Shnider, B. (1968) Management of patients with malignant lymphoma: a comparative study with cyclophosphamide and vinca alkaloids. Cancer Res. 28, 811ā€“822.

    CASĀ  PubMedĀ  Google ScholarĀ 

  50. Stutzman, L., Ezdinli, E. Z., and Stutzman, M. A. (1966) Vinblastine sulfate vs cyclophosphamide in the therapy for lymphoma. JAMA 195, 173ā€“178.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  51. Jackson, D. V., Jr., Spurr, C. L., Caponera, M. E., et al. (1987) Vinblastine infusion in non-Hodgkinā€™s lymphomas: lack of total cross-resistance with vincristine. Cancer Invest. 5, 535ā€“539.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  52. Sternberg, C. N., Yagoda, A., Scher, H. I., et al. (1989) Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer 64, 2448ā€“2458.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  53. Sternberg, C. N., Yagoda, A., Scher, H. I., et al. (1988) M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium. J. Urol. 139, 461ā€“469.

    CASĀ  PubMedĀ  Google ScholarĀ 

  54. Grossman, H. B., Natale, R. B., Tangen, C. M., et al. (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N. Engl. J. Med. 349, 859ā€“866.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  55. Epstein, J. B. and Scully, C. (1989) Intralesional vinblastine for oral Kaposi sarcoma in HIV infection. Lancet 2, 1100ā€“1101.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  56. Gill, P. S., Akil, B., Colletti, P., et al. (1989) Pulmonary Kaposiā€™s sarcoma: clinical findings and results of therapy. Am. J. Med. 87, 57ā€“61.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  57. Gregory, R. K. and Smith, I. E. (2000) Vinorelbine: a clinical review. Br. J. Cancer 82, 1907ā€“1913.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  58. The Elderly Lung Cancer Vinorelbine Italian Study Group. (1999) Effects of vinorelbine on quality of life and survival of elderly patients with advanced nonsmall-cell lung cancer. J. Natl. Cancer Inst. 91, 66ā€“72.

    ArticleĀ  Google ScholarĀ 

  59. Wozniak, A. J., Crowley, J. J., Balcerzak, S. P., et al. (1998) Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J. Clin. Oncol. 16, 2459ā€“2465.

    CASĀ  PubMedĀ  Google ScholarĀ 

  60. Arriagada, R., Bergman, B., Dunant, A., Le Chevalier, T., Pignon, J. P., and Vansteenkiste, J. (2004) Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N. Engl. J. Med. 350, 351ā€“360.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  61. Fumoleau, P., Delgado, F. M., Delozier, T., et al. (1993) Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J. Clin. Oncol. 11, 1245ā€“1252.

    CASĀ  PubMedĀ  Google ScholarĀ 

  62. Burstein, H. J., Harris, L. N., Marcom, P. K., et al. (2003) Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. J. Clin. Oncol. 21, 2889ā€“2895.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  63. Casey, E. B., Jellife, A. M., Le Quesne, P. M., and Millett, Y. L. (1973) Vincristine neuropathy. Clinical and electrophysiological observations. Brain 96, 69ā€“86.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  64. Bradley, W. G., Lassman, L. P., Pearce, G. W., and Walton, J. N. (1970) The neuromyopathy of vincristine in man. Clinical, electrophysiological and pathological studies. J. Neurol. Sci. 10, 107ā€“131.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  65. Weiss, H. D., Walker, M. D., and Wiernik, P. H. (1974) Neurotoxicity of commonly used antineoplastic agents (first of two parts). N. Engl. J. Med. 291, 75ā€“81.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  66. Slyter, H., Liwnicz, B., Herrick, M. K., and Mason, R. (1980) Fatal myeloencephalopathy caused by intrathecal vincristine. Neurology 30, 867ā€“871.

    CASĀ  PubMedĀ  Google ScholarĀ 

  67. Steurer, G., Kuzmits, R., Pavelka, M., Sinzinger, H., Fritz, E., and Ludwig, H. (1989) Early-onset thrombocytopenia during combination chemotherapy in testicular cancer is induced by vinblastine. Cancer 63, 51ā€“58.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  68. Gottlieb, R. J. and Cuttner, J. (1971) Vincristine-induced bladder atony. Cancer 28, 674ā€“675.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  69. Hansen, S. W. (1990) Autonomic neuropathy after treatment with cisplatin, vinblastine, and bleomycin for germ cell cancer. BMJ 300, 511ā€“512.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  70. Bostrom, B. (1988) Severe ileus from cisplatin and vinblastine infusion in neuroblastoma. J. Clin. Oncol. 6, 1356.

    CASĀ  PubMedĀ  Google ScholarĀ 

  71. Cvitkovic, E. and Izzo, J. (1992) The current and future place of vinorelbine in cancer therapy. Drugs 44, 36ā€“45.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  72. Lapeyre-Mestre, M., Gregoire, N., Bugat, R., and Montastruc, J. L. (2004) Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials. Fundam Clin. Pharmacol. 18, 97ā€“105.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  73. Besenval, M., Delgado, M., Demarez, J. P., and Krikorian, A. (1989) Safety and tolerance of Navelbine in phase Iā€“II clinical studies. Semin. Oncol. 16, 37ā€“40.

    CASĀ  PubMedĀ  Google ScholarĀ 

  74. Rowinsky, E. K., Onetto, N., Canetta, R. M., and Arbuck, S. G. (1992) Taxol: the first of the taxanes, an important new class of antitumor agents. Semin. Oncol. 19, 646ā€“662.

    CASĀ  PubMedĀ  Google ScholarĀ 

  75. Bissery, M. C., Nohynek, G., Sanderink, G. J., and Lavelle, F. (1995) Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience. Anticancer Drugs 6, 339ā€“368.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  76. Schiff, P. B., Fant, J., and Horwitz, S. B. (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277, 665ā€“667.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  77. Kumar, N. (1981) Taxol-induced polymerization of purified tubulin. Mechanism of action. J. Biol. Chem. 256, 10,435ā€“10,441.

    CASĀ  PubMedĀ  Google ScholarĀ 

  78. Manfredi, J. J. and Horwitz, S. B. (1984) Taxol: an antimitotic agent with a new mechanism of action. Pharmacol. Ther. 25, 83ā€“125.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  79. Jordan, M. A., Wendell, K., Gardiner, S., Derry, W. B., Copp, H., and Wilson, L. (1996) Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res. 56, 816ā€“825.

    CASĀ  PubMedĀ  Google ScholarĀ 

  80. Horwitz, S. B., Cohen, D., Rao, S., Ringel, I., Shen, H. J., and Yang, C. P. (1993) Taxol: mechanisms of action and resistance. J. Natl. Cancer Inst. Monogr. 55ā€“61.

    Google ScholarĀ 

  81. Dumontet, C., Duran, G. E., Steger, K. A., Beketic-Oreskovic, L., and Sikic, B. I. (1996) Resistance mechanisms in human sarcoma mutants derived by single-step exposure to paclitaxel (Taxol). Cancer Res. 56, 1091ā€“1097.

    CASĀ  PubMedĀ  Google ScholarĀ 

  82. Rowinsky, E. K., Donehower, R. C., Jones, R. J., and Tucker, R. W. (1988) Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res. 48, 4093ā€“4100.

    CASĀ  PubMedĀ  Google ScholarĀ 

  83. Giannakakou, P., Sackett, D. L., Kang, Y. K., et al. (1997) Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J. Biol. Chem. 272, 17,118ā€“17,125.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  84. Rowinsky, E. K., Burke, P. J., Karp, J. E., Tucker, R. W., Ettinger, D. S., and Donehower, R. C. (1989) Phase I and pharmacodynamic study of taxol in refractory acute leukemias. Cancer Res. 49, 4640ā€“4647.

    CASĀ  PubMedĀ  Google ScholarĀ 

  85. Wiernik, P. H., Schwartz, E. L., Strauman, J. J., Dutcher, J. P., Lipton, R. B., and Paietta, E. (1987) Phase I clinical and pharmacokinetic study of taxol. Cancer Res. 47, 2486ā€“2493.

    CASĀ  PubMedĀ  Google ScholarĀ 

  86. Wiernik, P. H., Schwartz, E. L., Einzig, A., Strauman, J. J., Lipton, R. B., and Dutcher, J. P. (1987) Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. J. Clin. Oncol. 5, 1232ā€“1239.

    CASĀ  PubMedĀ  Google ScholarĀ 

  87. Grem, J. L., Tutsch, K. D., Simon, K. J., et al. (1987) Phase I study of taxol administered as a short i.v. infusion daily for 5 days. Cancer Treat. Rep. 71, 1179ā€“1184.

    CASĀ  PubMedĀ  Google ScholarĀ 

  88. Donehower, R. C., Rowinsky, E. K., Grochow, L. B., Longnecker, S. M., and Ettinger, D. S. (1987) Phase I trial of taxol in patients with advanced cancer. Cancer Treat. Rep. 71, 1171ā€“1177.

    CASĀ  PubMedĀ  Google ScholarĀ 

  89. Rowinsky, E. K. (1995) Phamacology and metabolism, in Paclitaxel in Cancer Treatment, (McGuire, W. and Rowinsky, E. K., ed.), Dekker, New York, pp. 91ā€“120.

    Google ScholarĀ 

  90. Monsarrat, B., Mariel, E., Cros, S., et al. (1990) Taxol metabolism. Isolation and identification of three major metabolites of taxol in rat bile. Drug Metab. Dispos. 18, 895ā€“901.

    CASĀ  PubMedĀ  Google ScholarĀ 

  91. Rowinsky, E. K. and Donehower, R. C. (1995) Paclitaxel (taxol). N. Engl. J. Med. 332, 1004ā€“1014.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  92. Marre, F., Sanderink, G. J., de Sousa, G., Gaillard, C., Martinet, M., and Rahmani, R. (1996) Hepatic biotransformation of docetaxel (Taxotere) in vitro: involvement of the CYP3A subfamily in humans. Cancer Res. 56, 1296ā€“1302.

    CASĀ  PubMedĀ  Google ScholarĀ 

  93. Cortes, J. E. and Pazdur, R. (1995) Docetaxel. J. Clin. Oncol. 13, 2643ā€“2655.

    CASĀ  PubMedĀ  Google ScholarĀ 

  94. van Oosterom, A. T., Schrijvers, D., and Schriivers, D. (1995) Docetaxel (Taxotere), a review of preclinical and clinical experience. Part II: Clinical experience. Anticancer Drugs 6, 356ā€“368.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  95. Kohn, E. C., Sarosy, G., Bicher, A., et al. (1994) Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J. Natl. Cancer Inst. 86, 18ā€“24.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  96. Einzig, A. I., Wiernik, P. H., Sasloff, J., Runowicz, C. D., and Goldberg, G. L. (1992) Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma. J. Clin. Oncol. 10, 1748ā€“1753.

    CASĀ  PubMedĀ  Google ScholarĀ 

  97. Thigpen, J. T., Blessing, J. A., Ball, H., Hummel, S. J., and Barrett, R. J. (1994) Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study. J. Clin. Oncol. 12, 1748ā€“1753.

    CASĀ  PubMedĀ  Google ScholarĀ 

  98. Rowinsky, E. K., Gilbert, M. R., McGuire, W. P., et al. (1991) Sequences of taxol and cisplatin: a phase I and pharmacologic study. J. Clin. Oncol. 9, 1692ā€“1703.

    CASĀ  PubMedĀ  Google ScholarĀ 

  99. McGuire, W. P., Hoskins, W. J., Brady, M. F., et al. (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N. Engl. J. Med. 334, 1ā€“6.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  100. Eisenhauer, E. A., ten Bokkel Huinink, W. W., Swenerton, K. D., et al. (1994) European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J. Clin. Oncol. 12, 2654ā€“2666.

    CASĀ  PubMedĀ  Google ScholarĀ 

  101. Ozols, R. F., Bundy, B. N., Greer, B. E., et al. (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J. Clin. Oncol. 21, 3194ā€“3200.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  102. Neijt, J. P., Engelholm, S. A., Tuxen, M. K., et al. (2000) Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J. Clin. Oncol. 18, 3084ā€“3092.

    CASĀ  PubMedĀ  Google ScholarĀ 

  103. du Bois, A., Luck, H. J., Meier, W., et al. (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J. Natl. Cancer Inst. 95, 1320ā€“1329.

    PubMedĀ  Google ScholarĀ 

  104. Francis, P., Schneider, J., Hann, L., et al. (1994) Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer. J. Clin. Oncol. 12, 2301ā€“2308.

    CASĀ  PubMedĀ  Google ScholarĀ 

  105. Kaye, S. B., Piccart, M., Aapro, M., and Kavanagh, J. (1995) Docetaxel in advanced ovarian cancer: preliminary results from three phase II trials. EORTC Early Clinical Trials Group and Clinical Screening Group, and the MD Anderson Cancer Center. Eur. J. Cancer 31A, S14ā€“S17.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  106. Kavanagh, J. J., Kudelka, A. P., de Leon, C. G., et al. (1996) Phase II study of docetaxel in patients with epithelial ovarian carcinoma refractory to platinum. Clin. Cancer Res. 2, 837ā€“842.

    CASĀ  PubMedĀ  Google ScholarĀ 

  107. Piccart, M. J., Gore, M., Ten Bokkel Huinink, W., et al. (1995) Docetaxel: an active new drug for treatment of advanced epithelial ovarian cancer. J. Natl. Cancer Inst. 87, 676ā€“681.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  108. Vasey, P. A. (2003) Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. J. Clin. Oncol. 21, 136ā€“144.

    ArticleĀ  Google ScholarĀ 

  109. Niwa, Y., Nakanishi, T., Kuzuya, K., Nawa, A., and Mizutani, S. (2003) Salvage treatment with docetaxel for recurrent epithelial ovarian cancer. Int. J. Clin. Oncol. 8, 343ā€“347.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  110. Holmes, F. A., Walters, R. S., Theriault, R. L., et al. (1991) Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J. Natl. Cancer Inst. 83, 1797ā€“1805.

    CASĀ  PubMedĀ  Google ScholarĀ 

  111. Gianni, L., Munzone, E., Capri, G., et al. (1995) Paclitaxel in metastatic breast cancer: a trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines. J. Natl. Cancer Inst. 87, 1169ā€“1175.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  112. Bishop, J. F., Dewar, J., Toner, G. C., et al. (1999) Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J. Clin. Oncol. 17, 2355ā€“2364.

    CASĀ  PubMedĀ  Google ScholarĀ 

  113. Chevallier, B., Fumoleau, P., Kerbrat, P., et al. (1995) Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer. J. Clin. Oncol. 13, 314ā€“322.

    CASĀ  PubMedĀ  Google ScholarĀ 

  114. Dieras, V., Chevallier, B., Kerbrat, P., et al. (1996) A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC. European Organization for Research and Treatment of Cancer. Br. J. Cancer 74, 650ā€“656.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  115. Hudis, C. A., Seidman, A. D., Crown, J. P., et al. (1996) Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer. J. Clin. Oncol. 14, 58ā€“65.

    CASĀ  PubMedĀ  Google ScholarĀ 

  116. Trudeau, M. E., Eisenhauer, E. A., Higgins, B. P., et al. (1996) Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J. Clin. Oncol. 14, 422ā€“428.

    CASĀ  PubMedĀ  Google ScholarĀ 

  117. Seidman, A., Berry, D., Cirrincione, C., et al. (2004) American Society of Clinical Oncology. New Orleans, LA.

    Google ScholarĀ 

  118. Henderson, I. C., Berry, D. A., Demetri, G. D., et al. (2003) 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. 21, 976ā€“983.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  119. Martin, M., Pienkowski, T., Mackey, J., et al. (2005) Adjuvant docetaxel for node-positive breast cancer. N. Engl. J. Med. 352, 2302ā€“2313.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  120. Murphy, W. K., Fossella, F. V., Winn, R. J., et al. (1993) Phase II study of taxol in patients with untreated advanced non-small-cell lung cancer. J. Natl. Cancer Inst. 85, 384ā€“388.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  121. Fossella, F. V., Lee, J. S., Shin, D. M., et al. (1995) Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. J. Clin. Oncol. 13, 645ā€“651.

    CASĀ  PubMedĀ  Google ScholarĀ 

  122. Fossella, F. V., Lee, J. S., Murphy, W. K., et al. (1994) Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. J. Clin. Oncol. 12, 1238ā€“1244.

    CASĀ  PubMedĀ  Google ScholarĀ 

  123. Francis, P. A., Rigas, J. R., Kris, M. G., et al. (1994) Phase II trial of docetaxel in patients with stage III and IV non-small-cell lung cancer. J. Clin. Oncol. 12, 1232ā€“1237.

    CASĀ  PubMedĀ  Google ScholarĀ 

  124. Cerny, T., Kaplan, S., Pavlidis, N., et al. (1994) Docetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG). Br. J. Cancer 70, 384ā€“387.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  125. Kelly, K., Crowley, J., Bunn, P. A., Jr., et al. (2001) Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J. Clin. Oncol. 19, 3210ā€“3218.

    CASĀ  PubMedĀ  Google ScholarĀ 

  126. Shepherd, F. A., Dancey, J., Ramlau, R., et al. (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J. Clin. Oncol. 18, 2095ā€“2103.

    CASĀ  PubMedĀ  Google ScholarĀ 

  127. Belani, C. P., Choy, H., Bonomi, P., et al. (2005) Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J. Clin. Oncol. 23, 5883ā€“5891.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  128. Strauss, G., Herndon, J., Maddaus, M. A., et al. (2004) Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) protocol 9633 (abstract). Proc. Am. Soc. Clin. Oncol. 23, 621s.

    Google ScholarĀ 

  129. Smyth, J. F., Smith, I. E., Sessa, C., et al. (1994) Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur. J. Cancer 30A, 1058ā€“1060.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  130. Rowinsky, E. K. (1997) The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu. Rev. Med. 48, 353ā€“374.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  131. Tannock, I. F., de Wit, R., Berry, W. R., et al. (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl. J. Med. 351, 1502ā€“1512.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  132. Petrylak, D. P., Tangen, C. M., Hussain, M. H., et al. (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N. Engl. J. Med. 351, 1513ā€“1520.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  133. Motzer, R. J., Bajorin, D. F., Schwartz, L. H., et al. (1994) Phase II trial of paclitaxel shows antitumor activity in patients with previously treated germ cell tumors. J. Clin. Oncol. 12, 2277ā€“2283.

    CASĀ  PubMedĀ  Google ScholarĀ 

  134. Kondagunta, G. V., Bacik, J., Donadio, A., et al. (2005) Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J. Clin. Oncol. 23, 6549ā€“6555.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  135. Roth, B. J., Dreicer, R., Einhorn, L. H., et al. (1994) Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group. J. Clin. Oncol. 12, 2264ā€“2270.

    CASĀ  PubMedĀ  Google ScholarĀ 

  136. Dimopoulos, M. A., Papadimitriou, C. A., Georgoulias, V., et al. (2000) Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol. Oncol. 78, 52ā€“57.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  137. Hoskins, P. J., Swenerton, K. D., Pike, J. A., et al. (2001) Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J. Clin. Oncol. 19, 4048ā€“4053.

    CASĀ  PubMedĀ  Google ScholarĀ 

  138. Gill, P. S., Tulpule, A., Espina, B. M., et al. (1999) Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposiā€™s sarcoma. J. Clin. Oncol. 17, 1876ā€“1883.

    CASĀ  PubMedĀ  Google ScholarĀ 

  139. Hensley, M. L., Maki, R., Venkatraman, E., et al. (2002) Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J. Clin. Oncol. 20, 2824ā€“2831.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  140. Urba, S. G., Orringer, M. B., Ianettonni, M., Hayman, J. A., and Satoru, H. (2003) Concurrent cisplatin, paclitaxel, and radiotherapy as preoperative treatment for patients with locoregional esophageal carcinoma. Cancer 98, 2177ā€“2183.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  141. El-Rayes, B. F., Shields, A., Zalupski, M., et al. (2004) A phase II study of carboplatin and paclitaxel in esophageal cancer. Ann. Oncol. 15, 960ā€“965.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  142. Clark, J. I., Hofmeister, C., Choudhury, A., et al. (2001) Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma. Cancer 92, 2334ā€“2340.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  143. Fountzilas, G., Skarlos, D., Athanassiades, A., et al. (1997) Paclitaxel by threehour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group. Ann. Oncol. 8, 451ā€“455.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  144. Rowinsky, E. K., Eisenhauer, E. A., Chaudhry, V., Arbuck, S. G., and Donehower, R. C. (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin. Oncol. 20, 1ā€“15.

    CASĀ  PubMedĀ  Google ScholarĀ 

  145. Weiss, R. B., Donehower, R. C., Wiernik, P. H., et al. (1990) Hypersensitivity reactions from taxol. J. Clin. Oncol. 8, 1263ā€“1268.

    CASĀ  PubMedĀ  Google ScholarĀ 

  146. Rowinsky, E. K., Chaudhry, V., Cornblath, D. R., and Donehower, R. C. (1993) Neurotoxicity of Taxol. J. Natl. Cancer Inst. Monogr. 15, 107ā€“115.

    PubMedĀ  Google ScholarĀ 

  147. Rowinsky, E. K., McGuire, W. P., Guarnieri, T., Fisherman, J. S., Christian, M. C., and Donehower, R. C. (1991) Cardiac disturbances during the administration of taxol. J. Clin. Oncol. 9, 1704ā€“1712.

    CASĀ  PubMedĀ  Google ScholarĀ 

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Zelnak, A.B. (2007). Clinical Pharmacology and Use of Microtubule-Targeting Agents in Cancer Therapy. In: Zhou, J. (eds) Microtubule Protocols. Methods in Molecular Medicineā„¢, vol 137. Humana Press. https://doi.org/10.1007/978-1-59745-442-1_15

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