Docetaxel for Metastatic Cancer and Its Role in Combination Therapies for Advanced Prostate Cancer

  • Ellen K. Wasan
  • Martin Gleave
  • Karen Fang
  • Kim Chi
  • Gwyn Bebb
  • Lincoln Edwards
  • Marcel B. Bally
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Although strides have been made in the diagnosis and treatment of cancer in the past few decades, advanced, metastatic cancer remains extremely difficult to treat. Obviously, a major hurdle in improving survival is the treatment or prevention of metastatic disease, either to eliminate it completely or to contain it like other chronic diseases. To reach the metastatic stage, the cancer cells undergo many and various changes in the usual regulatory mechanisms governing cellular proliferation and apoptosis, resulting in great heterogeneity. Therein lies the challenge in developing appropriate and effective combination therapies for metastatic disease that utilize multiple mechanisms to overcome resistance to cell death. In this chapter, the relatively new cytotoxic taxane docetaxel will be discussed in the context of its current role in treating metastatic cancer and its future role in combination with novel, molecularly targeted chemotherapeutic agents.


Prostate Cancer Vascular Endothelial Growth Factor Clin Oncol Metastatic Breast Cancer Prostate Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jewett MA, Khakpour G, Moore MJ. Supportive care is not the only option in prostate cancer patients resistant to hormone therapy: the argument against. Eur Urol 1996; 29(Suppl 2):45–48.PubMedGoogle Scholar
  2. 2.
    Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol 2002; 168(6):2439–2443.PubMedCrossRefGoogle Scholar
  3. 3.
    Oh WK, Halabi S, Kelly WK, Werner C, Godley PA, Vogelzang NJ, et al. Cancer and Leukemia Group B 99813. A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813. Cancer 2003; 98(12): 2592–2598.PubMedCrossRefGoogle Scholar
  4. 4.
    Petrylak DP, Macarthur R, O’Connor J, Shelton G, Weitzman A, Judge T, et al. Phase I/II studies of docetaxel (Taxotere) combined with estramustine in men with hormone-refractory prostate cancer. Semin Oncol 1999; 26(5 Suppl 17):28–33.PubMedGoogle Scholar
  5. 5.
    Herbst RS, Khuri FR. Mode of action of docetaxel-a basis for combination with novel anticancer agents. Cancer Treat Rev 2003; 29:407–415.PubMedCrossRefGoogle Scholar
  6. 6.
    Schimming, R, Mason KA, Hunter N, Weil M, Kishi K, Milas L. Lack of correlation between mitotic arrest or apoptosis and antitumor effect of docetaxel. Cancer Chemother Pharmacol 1999; 43(2):165–172.PubMedCrossRefGoogle Scholar
  7. 7.
    Lavelle F, Bissery MC, Combeau C, Riou JF, Vrignaud P, Andre S. Preclinical evaluation of docetaxel (Taxotere). Semin Oncol 1995; 22(2 Suppl 4):3–16.Google Scholar
  8. 8.
    Cory S. Regulation of lymphocyte survival by the Bcl-2 gene family. Ann Rev Immunol 1995; 13: 513–543.CrossRefGoogle Scholar
  9. 9.
    Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 1997; 3(6): 614–620.PubMedCrossRefGoogle Scholar
  10. 10.
    Reed JC. Bcl-2 and the regulation of programmed cell death. J Cell Biol 1994; 124:1–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Reed JC. Bcl-2 family proteins: strategies for overcoming chemoresistance in cancer. Adv Pharmacol 1997; 41:501–532.PubMedCrossRefGoogle Scholar
  12. 12.
    Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456–1462.PubMedCrossRefGoogle Scholar
  13. 13.
    Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the Bcl-2 family and cell death. Blood 1996; 88:386–401.PubMedGoogle Scholar
  14. 14.
    Vander Heiden MG, Thompson CB. Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis? Nat Cell Biol 1999;1:E209–E216.CrossRefGoogle Scholar
  15. 15.
    Hsu Y-T, Wolter KG, Youle RJ. Cytosol-to-membrane redistribution of Bax and Bcl-XL during apoptosis. Proc Nat Acad Sci USA 1997; 94:3668–3672.PubMedCrossRefGoogle Scholar
  16. 16.
    Wolter KG. Hsu Y-T, Smith CL, Nechushtan A, Xi X-G, Youle RJ Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 1997; 139:1281–1292.PubMedCrossRefGoogle Scholar
  17. 17.
    Gross A, Jockel J, Wei MC, Korsmeyer SJ. Enforced dimerization of Bax results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J 1998; 17:3878–3885.PubMedCrossRefGoogle Scholar
  18. 18.
    Nechushtan A, Smith CL, Hsu Y-T, Youle RJ Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 1999; 18:2330–2341.PubMedCrossRefGoogle Scholar
  19. 19.
    Manon S, Chaudhuri B, Guerin M. Release of cytochrome c and decrease of cytochrome c oxidase in Bax-expressing yeast cells and prevention of these effects by coexpression of Bcl-XL. FEBS Lett 1997; 415:29–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Antonsson B, Montessuit S, Sanchez B, Martinou JC. Bax is present as a high molecular weight oligomer-complex in the mitochondrial membrane of apoptotic cells. J Biol Chem 2001; 2765:11,615–11,623.CrossRefGoogle Scholar
  21. 21.
    Mikhailov V, Mikhailova M, Pulkrabek DJ, Dong Z, Venkatachalam MA, Saikumar P. Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem 2001; 276:18,361–18,374.PubMedCrossRefGoogle Scholar
  22. 22.
    Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Manzoor A, Emad S, et al. Cell Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91:479–489.PubMedCrossRefGoogle Scholar
  23. 23.
    Oltval ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74:609–619.CrossRefGoogle Scholar
  24. 24.
    Hou Q, Cymbalyuk E, Hsu S-C, Xu M, Hsu Y-T. Apoptosis modulatory activities of transiently expressed Bcl-2: Roles in cytochrome c release and Bax regulation. Apoptosis 2003; 8:617–629.PubMedCrossRefGoogle Scholar
  25. 25.
    Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 1995; 80:285–291.PubMedCrossRefGoogle Scholar
  26. 26.
    Shitashige M, Toi M, Yano T, Shibata M, Matsuo Y, Shibasaki F. Dissociation of Bax from a BCl-2/Bax heterodimer triggered by phosphorylation of serine 70 of Bcl-2. J Biochemistry (Tokyo) 2001; 130(6): 741–748.Google Scholar
  27. 27.
    Wang Q, Weider R. All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells. Oncogene 2004; 23(2):426–433.PubMedCrossRefGoogle Scholar
  28. 28.
    Schimming R, Mason KA, Hunter N, Weil M, Kishi K, Milas L. Lack of correlation between mitotic arrest or apoptosis and antitumor effect of docetaxel. Cancer Chemother Pharmacol 1999; 43(2):165–172.PubMedCrossRefGoogle Scholar
  29. 29.
    Hartley-Asp B, Kruse E. Nuclear protein matrix as a target for estramustine-induced cell death. Prostate 1986; 9:387–395.PubMedCrossRefGoogle Scholar
  30. 30.
    Pienta KJ, Lehr JE. Inhibition of prostate cancer growth by estramustine and etoposide: evidence for interaction at the nuclear matrix. J Urol 1993; 149:1622–1625.PubMedGoogle Scholar
  31. 31.
    Hartley-Asp, B. Estramustine-induced mitotic arrest in two human prostatic carcinoma cell lines DU-145 and PC-3. Prostate 1984; 5:93–100.PubMedCrossRefGoogle Scholar
  32. 32.
    Kraus LA, Samuel SK, Schmid SM, Dykes DJ, Waud WR, Bissery MC. The mechanism of action of docetaxel (Taxotere) in xenograft models is not limited to bcl-2 phosphorylation. Investigational New Drugs 2003; 21(3): 259–268.PubMedCrossRefGoogle Scholar
  33. 33.
    Maestre N, Bezombes C, Plo I, Levied T, Lavelle F, Laurent G, Jaffrezou JP. Phosphatidylcholine-derived phosphatidic acid and diacylglycerol are involved in the signaling pathways activated by docetaxel. J Exp Ther Oncol 2003; 3(1):36–46.PubMedCrossRefGoogle Scholar
  34. 34.
    Sweeney CJ, Miller KD, Sissons SE, Nozaki S, Heilman DK, Shen J, Sledge GW Jr. The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors. Cancer Res 2001; 61(8): 3369–3372.PubMedGoogle Scholar
  35. 35.
    Vacca A, Ribatti D, Iurlaro M, Merchionne F, Nico B, Ria R, Dammacco F. Docetaxel versus paclitaxel for antiangiogenesis. J Hematother Stem Cell Res 2002; 11(1):103–118.PubMedCrossRefGoogle Scholar
  36. 36.
    Avramis IA, Kwock R, Avramis VI. Taxotere and vincristine inhibit the secretion of the angiogenesis inducing vascular endothelial growth factor (VEGF) by wild-type and drug-resistant human leukemia T-cell lines. Anticancer Res 2001; 21(4A):2281–2286.PubMedGoogle Scholar
  37. 37.
    Guo XL, Lin GJ, Zhao H, Gao Y, Qian LP, Xu SR, et al. Inhibitory effects of docetaxel on expression of VEGF, bFGF and MMPs of LS174T cell. World J Gastroenterol 2003; 9(9):1995–1998.PubMedGoogle Scholar
  38. 38.
    Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, et al. Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 2003; 63(15):4342–4346.PubMedGoogle Scholar
  39. 39.
    Man S, Bocci G, Francia G, Green SK, Jothy S, Hanahan D, et al. Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 2002; 62(10):2731–2735.PubMedGoogle Scholar
  40. 40.
    Inoue K, Chikazawa M, Fukata S, Yoshikawa C, Shuin T. Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. Clin Cancer Res 2003; 9(2):886–899.PubMedGoogle Scholar
  41. 41.
    Koukourakis MI, Simopoulos C, Polychronidis A, Perente S, Botaitis S, Giatromanolaki A, et al. The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status? Anticancer Res 2003; 23(2C):1673–1680.PubMedGoogle Scholar
  42. 42.
    Salimichokami M. Combining angiogenesis inhibitors with cytotoxic chemotherapy enhances PSA response in hormone refractory prostate cancer (HRPC), a randomized study of weekly docetaxel alone or in combination with thalidomide. Proc Am Soc Clin Oncol 2003; 22:429 (abstract no. 1725).Google Scholar
  43. 43.
    Dai J, Kitagawa Y, Zhang J, Yao Z, Mizokami A, Cheng S, et al. Vascular endothelial growth factor contributes to the prostate cancer-induced osteoblast differentiation mediated by bone morphogenetic protein. Cancer Res 2004; 64(3):994–999.PubMedCrossRefGoogle Scholar
  44. 44.
    Cassidy PB, Moos PJ Kelly RC, Fitzpatrick FA. Cyclooxygenase-2 induction by paclitaxel, docetaxel and taxane analogues in human monocytes and murine macrophages: structure-activity relationships and their implications. Clinical Cancer Res 2002; 8(3):846–855.Google Scholar
  45. 45.
    Tsavaris N, Kosmas C, Vadiaka M, Kanelopoulos, Boulamatsis D. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer 2002; 87(1):21–27.PubMedCrossRefGoogle Scholar
  46. 46.
    Tong AW, Seamour B, Lawson JM, Ordonez G, Vukelja S, Hyman W, et al. Cellular immune profile of patients with advanced cancer before and after taxane treatment. Am J Clin Oncol 2000; 23(5):463–472.PubMedGoogle Scholar
  47. 47.
    Chan OT, Yang LX. The immunological effects of taxanes. Cancer Immunol Immunother 2000; 49(4-5):181–185.PubMedCrossRefGoogle Scholar
  48. 48.
    Rosing H, Lustig V, van Warmerdam LJ, Huizing MT, ten Bokkel Huinink WW, Schellens JH, et al. Pharmacokinetics and metabolism of docetaxel administered as a 1-h intravenous infusion. Cancer Chemother Pharmacol 2000; 45(3):213–218.PubMedCrossRefGoogle Scholar
  49. 49.
    Bruno R, Riva D, Hille A, Lebecq A, Thomas L. Pharmacokinetic and pharmacodynamic properties of docetaxel: Results of phase I and phase II trials. Am J Health-Syst Pharm 54 1997; (Suppl. 2):S16–S19.Google Scholar
  50. 50.
    Bruno R, Mille D, Riva A, Vivier N, ten Bokkel Huinink WW, van Oosterom AT, et al. Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 1998; 16:187–196.PubMedGoogle Scholar
  51. 51.
    Hirth J, Watkins PB, Strawderman M, et al. The effect of an individual’s cytochrome CYP3A4 activity on docetaxel clearance. Clin Cancer Res 2000; 6(4):1255–1258.PubMedGoogle Scholar
  52. 52.
    Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH. Preclinical pharmacokinetics of paclitaxel and docetaxel. Anticancer Drugs 1998; 9(1):1–17.PubMedCrossRefGoogle Scholar
  53. 53.
    Aventis Pharmaceuticals, Inc. Taxotere® package insert. 2003.Google Scholar
  54. 54.
    Ramos M, Gonzalez-Ageitos A, Amenedo M, Gonzalez-Quintas A, Gamazo JL, Togores P, et al. Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment. J Chemother 2003; 15(2):192–197.PubMedGoogle Scholar
  55. 55.
    Mey U, Gorschluter M, Ziske C, Kleinschmidt R, Glasmacher A, Schmidt-Wolf IG. Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial. Anticancer Drugs 2003; 14(3):233–238.PubMedCrossRefGoogle Scholar
  56. 56.
    Masters GA, Brockstein BE, Mani S, Ratain MJ. Phase 1 dose escalation study of docetaxel with filgrastim support in patients with advanced solid tumors. Med Oncol 2003; 20(1):7–12.PubMedCrossRefGoogle Scholar
  57. 57.
    Kuroi K, Shimozuma K. Neurotoxicity of taxanes: symptoms and quality of life assessment. Breast Cancer 2004; 11(1):92–99.PubMedCrossRefGoogle Scholar
  58. 58.
    Pronk LC, Hilkens PH, van den Bent MJ, van Putten WL, Stoter G, Verweij J. Corticosteroid comedication does not reduce the incidence and severity of neurotoxicity induced by docetaxel. Anticancer Drugs 1998; 9(9):759–764.PubMedCrossRefGoogle Scholar
  59. 59.
    Wasner G, Hilpert F, Schattschneider J, Binder A, Pfisterer J, Baron R. Docetaxel-induced nail changes—a neurogenic mechanism: a case report. J Neurooncol 2002; 58(2):167–174.PubMedCrossRefGoogle Scholar
  60. 60.
    Peccart, M. The role of taxanes in the adjuvant treatment of early stage breast cancer. Breast Cancer Res Treat 2003; 79(Suppl 1):S25–34.CrossRefGoogle Scholar
  61. 61.
    Hutcheon AW, Heys SD, Sarkar TK, Aberdeen Breast Group. Neoadjuvant docetaxel in locally advanced breast cancer. Breast Cancer Res Treat 2003; 79(Suppl 1):S19–24.PubMedCrossRefGoogle Scholar
  62. 62.
    Fumoleau, P. Efficacy and safety of docetaxel in clinical trials. Am J Health-Syst Pharm 1997; 54(Suppl 2):S19–24.PubMedGoogle Scholar
  63. 63.
    Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol 2003; 21(6):968–975.PubMedCrossRefGoogle Scholar
  64. 64.
    Chan S, Friedrichs K, Noel D, Pinter T, Van Belle S, Vorobiof D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17(8): 2341–2354.PubMedGoogle Scholar
  65. 65.
    Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschenes L, Douma J, et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 1999; 17(5):1413–1424.PubMedGoogle Scholar
  66. 66.
    Sjöström J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson-Lönn S, Bengtsson NO, et al. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 1999; 35(8):1194–1201.PubMedCrossRefGoogle Scholar
  67. 67.
    Bonneterre J, Roche H, Monnier A, Guastalla JP, Namer M, Fargeot P, et al. Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure. Br J Cancer 2002; 87: 1210–1215.PubMedCrossRefGoogle Scholar
  68. 68.
    Mackey JR, Paterson A, Dirix LY, Dewar J, Chap L, Miguel M, et al. Final results of the phase III randomized trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) to FAC as first line chemotherapy (CT) to patients (pts) with metastatic breast cancer (MBC). American Society of Clinical Oncology Annual Meeting, 2002 (abstract 137).Google Scholar
  69. 69.
    O’Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002; 20(12):2812–2823.PubMedCrossRefGoogle Scholar
  70. 70.
    Nabholtz JM. Docetaxel-anthracycline combinations in metastatic breast cancer. Breast Cancer Res Treat 2003; 79(Suppl 1):S3–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Goble S, Bear HD. Emerging role of taxanes in adjuvant and neoadjuvant therapy for breast cancer: the potential and the questions. Surg Clin North Am 2003; 83(4):943–971.PubMedCrossRefGoogle Scholar
  72. 72.
    Perotti A, Cresta S, Grasselli G, Capri G, Minotti G, Gianni L. Cardiotoxic effects of anthracyclinetaxane combinations. Expert Opin Drug Saf 2003; 2(1):59–71.PubMedGoogle Scholar
  73. 73.
    Fumoleau P. Gemcitabine combined with docetaxel in metastatic breast cancer. Semin Oncol 2003; 30(2 Suppl 3):15–18.PubMedGoogle Scholar
  74. 74.
    Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients form 52 randomised clinical trials. BMJ 1995; 311:899–909.Google Scholar
  75. 75.
    Rapp E, Pater JL, Willan A, et al. Chemotherapy can prolong survival in patients with advanced non-small cell lung cancer-report of a Canadian multicenter randomized trial. J Clin Oncol 1988; 6:633–641.PubMedGoogle Scholar
  76. 76.
    ASCO Special Article. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. J Clin Oncol 1997; 15:2996–3018.Google Scholar
  77. 77.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346(2):92–98.PubMedCrossRefGoogle Scholar
  78. 78.
    Belani CP. Chemotherapy regimens in advanced non small-cell lung cancer: recent randomized trials. Clin Lung Cancer 2000; 2(Suppl 1):S7–S10.PubMedGoogle Scholar
  79. 79.
    Manegold C, Pilz L, Koschel G, Schott K, Hruska D, Mezger J. Single agent gemcitabine and docetaxel given sequentially in various doses and schedules are effective in advanced NSCLC: survival data from two randomized phase II studies. American Society of Clinical Oncology Annual Meeting, 2001; 337a, abstract 1346.Google Scholar
  80. 80.
    Simon GR, Bunn PA Jr. Taxanes in the treatment of advanced (stage III and IV) non-small cell lung cancer (NSCLC): recent developments. Cancer Invest 2003; 21(1):87–104.PubMedCrossRefGoogle Scholar
  81. 81.
    Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol 2004; 22(2):254–261.PubMedCrossRefGoogle Scholar
  82. 82.
    Fossella F. Docetaxel + Cisplatin (DC) and Docetaxel + Carboplatin (DCCb) vs Vinorelbine + Cisplatin (VC) in chemotherapy-naïve patients with advanced and metastatic non-small cell lung cancer (NSCLC): results of a multicenter, randomized phase III study. Eur J Cancer 2001; 37(Suppl.6):154.CrossRefGoogle Scholar
  83. 83.
    Gralla RJ. Docetaxel trials in non-small-cell carcinoma of the lung, In: Johnson DH, Klastersky J, eds. Taxanes in Lung Cancer Therapy. New York: Marcel Dekker, 1998:103–116.Google Scholar
  84. 84.
    Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, et al. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer 2000; 27(3): 145–57.PubMedCrossRefGoogle Scholar
  85. 85.
    Hainsworth JD, Burris HA 3rd, Greco FA. Weekly docetaxel as a single agent and in combination with gemcitabine in elderly and poor performance status patients with advanced non-small cell lung cancer. Semin Oncol 2001; 28(3 Suppl 9):21–25.PubMedCrossRefGoogle Scholar
  86. 86.
    Murren JR, Davies M. Irinotecan and taxane combinations for non small-cell lung cancer. Clin Lung Cancer 2001; 2(Suppl 2):S20–25.PubMedGoogle Scholar
  87. 87.
    Miller VA. Trials of vinorelbine and docetaxel in the treatment of advanced non small-cell lung cancer. Clin Lung Cancer 2000; 1(Suppl 1):S24–26.PubMedCrossRefGoogle Scholar
  88. 88.
    Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O’Rourke M, et al. 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 2000; 18(10):2095–2103.PubMedGoogle Scholar
  89. 89.
    Lynch TJ Jr. Review of two phase II randomized trials of single-agent docetaxel in previously treated advanced non-small cell lung cancer. Semin Oncol 2001; 28(3 Suppl 9):5–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000; 18(12):2354–2362.PubMedGoogle Scholar
  91. 91.
    Hanna NH, Shepherd FA, Rosell JR, Pereira F, et al. A phase III study of permetrexed vs. docetraxel in patients with recurrent non-small cell lung cancer (NSCLC) who were previously treated with chemotherapy. Proc Am Soc Clin Oncol 2003; 22:622.Google Scholar
  92. 92.
    Fossella, FV. Pemetrexed for treatment of advanced non-small cell lung cancer. Semin Oncol 2004; 31(1 Suppl 1):100–105.PubMedCrossRefGoogle Scholar
  93. 93.
    Johnson DH. Gefitinib (Iressa) trials in non-small cell lung cancer. Lung Cancer 2003; 41(Suppl 1):S23–28.PubMedCrossRefGoogle Scholar
  94. 94.
    Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 2. J Clin Oncol 2004; 22(5):785–794.PubMedCrossRefGoogle Scholar
  95. 95.
    Lara PN Jr, Laptalo L, Longmate J, Lau DH, Gandour-Edwards R, Gumerlock PH, et al. Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a California Cancer Consortium screening and phase II trial. Clin Lung Cancer 2004; 5(4):231–236.PubMedGoogle Scholar
  96. 96.
    Au NHC, Cheang M, Huntsman DG, Yorida E, Coldman A, Elliott WM, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. Br J Pathol 2004; in press.Google Scholar
  97. 97.
    Rudin CM, Otterson GA, Mauer AM, Villalona-Calero MA, Tomek R, Prange B, et al. A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell lung cancer. Ann Oncol 2002; 13(4):539–545.PubMedCrossRefGoogle Scholar
  98. 98.
    Gandara DR, Lara PN Jr, Goldberg Z, Lau DH. Integration of new chemotherapeutic agents into chemoradiotherapy for stage III non-small cell lung cancer: focus on docetaxel. Semin Oncol 2001; 28(3 Suppl 9):26–32.PubMedCrossRefGoogle Scholar
  99. 99.
    Camps C, Massuti A, Jimenez AM, Maestu I, Almenar D, Garcia R, et al. Second-line docetaxel administrated every 3 weeks versus weekly in advanced non-small-cell lung cancer (NSCLC): a Spanish Lung Cancer Group (SLCG) phase III trial. Proc of Am Soc Clin Oncol 2003; 22:625, (abstract no. 2514).Google Scholar
  100. 100.
    Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, et al. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet 2001; 357(9267):1478–1484.PubMedCrossRefGoogle Scholar
  101. 101.
    Kakolyris X, Tsiafaki A, Agelidou J, Arapis J, Boukovinas N, Samaras P, et al. Preliminary results of a multicenter randomized phase III trial of docetaxel plus gemcitabine (DG) versus vinorelbine plus cisplatin (VC) in patients with advanced non-small cell lung cancer. American Society of Clinical Oncology Annual Meeting, 2002 (abstract 1182).Google Scholar
  102. 102.
    Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003; 21(16):3016–3024.PubMedCrossRefGoogle Scholar
  103. 103.
    Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer 1994;30A(8):1058–1060.PubMedCrossRefGoogle Scholar
  104. 104.
    Seibel NL, Blaney SM, O’Brien M, Krailo M, Hutchinson R, Mosher RB, et al. Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children’s Cancer Group trial. Clin Cancer Res 1999; 5(4): 733–737.PubMedGoogle Scholar
  105. 105.
    Blaney SM, Seibel NL, O’Brien M, Reaman GH, Berg SL, Adamson PC, et al. Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children’s Cancer Group trial. J Clin Oncol 1997; 15(4):1538–1543.PubMedGoogle Scholar
  106. 106.
    Kavanagh JJ. Docetaxel in the treatment of ovarian cancer. Oncology 2002; 16(6 Suppl): 73–82.PubMedGoogle Scholar
  107. 107.
    Schull B, Kornek GV, Schmid K, Raderer M, Hejna M, Lenauer A, et al. Effective combination chemotherapy with bimonthly docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer. Oncology 2003; 65(3):211–217.PubMedCrossRefGoogle Scholar
  108. 108.
    Haller DG, Misset JL. Docetaxel in advanced gastric cancer. Anticancer Drugs 2002; 13(5): 451–460.PubMedCrossRefGoogle Scholar
  109. 109.
    Einzig AI, Schuchter LM, Recio A, Coatsworth S, Rodriquez R, Wiernik PH. Phase II trial of docetaxel (Taxotere) in patients with metastatic melanoma previously untreated with cytotoxic chemotherapy. Med Oncol 1996; 13(2):111–117.PubMedGoogle Scholar
  110. 110.
    McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol 1997; 15(5): 1853–1857.PubMedGoogle Scholar
  111. 111.
    de Wit R, Kruit WH, Stoter G, de Boer M, Kerger J, Verweij J. Docetaxel (Taxotere): an active agent in metastatic urothelial cancer; results of a phase II study in non-chemotherapy-pretreated patients. Br J Cancer 1998; 78(10):1342–1345.PubMedGoogle Scholar
  112. 112.
    Dimopoulos MA, Deliveliotis C, Moulopoulos LA, Papadimitriou C, Mitropoulos D, Anagnostopoulos A, et al. Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel. Urology 1998; 52(1):56–60.PubMedCrossRefGoogle Scholar
  113. 113.
    Pectasides D, Visvikis A, Aspropotamitis A, et al. Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cell urothelial cancer. Phase II trial. Eur J Cancer 2000; 36(1):74–79.PubMedCrossRefGoogle Scholar
  114. 114.
    Sengelov L, Kamby C, Lund B, Engelholm SA. Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study. J Clin Oncol 1998; 16(10):3392–3397.PubMedGoogle Scholar
  115. 115.
    Dimopoulos MA, Bakoyannis C, Georgoulias V, et al. Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: a multicenter phase II study of the Hellenic Cooperative Oncology Group. Ann Oncol 1999; 10(11):1385–1388.PubMedCrossRefGoogle Scholar
  116. 116.
    De Muro XG, Marcuello E, Climent MA, Paz-Ares L, Parra S, Guma J, et al. Phase II study of docetaxel and cisplatin in advanced urothelial cancer: preliminary results. Proceedings of American Society of Clinical Oncology, 1999 (abstract no. 1306).Google Scholar
  117. 117.
    Couteau C, Chouaki N, Leyvraz S, et al. A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck. Br J Cancer 1999; 81(3):457–462.PubMedCrossRefGoogle Scholar
  118. 118.
    Kaye SB, Piccart M, Aapro M, et al. Phase II trials of docetaxel (Taxotere) in advanced ovarian cancer—an updated overview. Eur J Cancer 1997; 33(13):2167–2170.PubMedCrossRefGoogle Scholar
  119. 119.
    Vorobiof DA, Chasen MR, Abratt RP, et al. Phase II trial of single agent taxotere (T) in malignant pleural mesothelioma (MPM) (meeting abstract). Proc Am Soc Clin Oncol 2000; 19:578a.Google Scholar
  120. 120.
    Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. Cancer J Clin 2003; 53(1):5–26.Google Scholar
  121. 121.
    D’amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280(11): 969–974.CrossRefGoogle Scholar
  122. 122.
    Tannock IF, Osobad D, Stockler MR, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996; 14(6):1756–1764.PubMedGoogle Scholar
  123. 123.
    Kantoff PW, Halabi S, Conaway M, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol 1999; 17(8):2506–2513.PubMedGoogle Scholar
  124. 124.
    Beer TM, Pierce WC, Lowe BA, et al. Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol 2001; 12(9):1273–1279.PubMedCrossRefGoogle Scholar
  125. 125.
    Picus J, Schultz M. Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol 1999; 26(5 Suppl 17):14–18.PubMedGoogle Scholar
  126. 126.
    Friedland D, Cohen J, Miller R Jr, Voloshin M, Gluckman R, Lembersky B, et al. A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2. Semin Oncol 1999; 26(5 Suppl 17):19–23.PubMedGoogle Scholar
  127. 127.
    Berry W, Dakhil S, Gregurich MA, Asmar L. Phase II trial of single-agent weekly docetaxel in hormone-refractory, symptomatic, metastatic carcinoma of the prostate. Semin Oncol 2001; 28(4 Suppl 15): 8–15.PubMedCrossRefGoogle Scholar
  128. 128.
    Savarese DM, Halabi S, Hars V, Akerley WL, Taplin ME, Godley PA, et al. Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B. J Clin Oncol 2001; 19(9):2509–2516PubMedGoogle Scholar
  129. 129.
    Petrylak DP, Macarthur R, O’Connor J, Shelton G, Weitzman A, Judge T, et al. Phase I/II studies of docetaxel (Taxotere) combined with estramustine in men with hormone-refractory prostate cancer. Semin Oncol 1999; 26(5 Suppl 17):28–33.PubMedGoogle Scholar
  130. 130.
    Natale R, Zarestsky S. Phase I/II trial of estramustine (E) and taxotere (T) in patients with metastatic hormone-refractory prostate cancer (HRPC). (Meeting abstract). American Society of Clinical Oncology Annual Meeting, 1999 (abstract no. 1343).Google Scholar
  131. 131.
    Kosty MP, Ferreira A, Bryntesen A. Weekly docetaxel and low-dose estramustine phosphate in hormone refractory prostate cancer: a phase II study. Amercan Society of Clinical Oncology Annual Meeting, 2001 (abstract no. 2360).Google Scholar
  132. 132.
    Scholz MC, Guess B, Barrios F, Strum S, Leibowitz R. Low-dose single-agent weekly docetaxel (taxotere) is effective and well tolerated in elderly men with prostate cancer. American Society of Clinical Oncology Annual Meeting, 2001 (abstract no. 2441).Google Scholar
  133. 133.
    Gulley J, Dahut W. Novel clinical trials in androgen-independent prostate cancer. Clin Prostate Cancer 2002; 1(1):51–57.PubMedGoogle Scholar
  134. 134.
    Yonou H, Yokose T, Kamijo T, Kanomata N, Hasebe T, Nagai K, et al. Establishment of a novel species-and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone. Cancer Res 2001; 61(5):2177–2182.PubMedGoogle Scholar
  135. 135.
    Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, et al. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 1994; 54(10): 2577–2581.PubMedGoogle Scholar
  136. 136.
    Soos G, Jones RF, Haas GP, Wang CY. Comparative intraosseal growth of human prostate cancer cell lines LNCaP and PC-3 in the nude mouse. Anticancer Res 1997; 17(6D):4253–4258.PubMedGoogle Scholar
  137. 137.
    Gleave ME, Hsieh JT, Gao C, von Eschenbach AC, Chung LWK. Acceleration of human prostate carcinoma growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res 1991; 51:375–3761.Google Scholar
  138. 138.
    Gleave ME, Hsieh JT, von Eschenbach AC, Chung LWK. Prostate and bone fibroblasts induce human prostate cancer growth in vivo: Implications for bidirectional stromal-epithelial interaction in prostate carcinoma growth and metastasis. J Urol 1992; 147:1151–1159.PubMedGoogle Scholar
  139. 139.
    Pettaway CA, Pathak S, Greene G, Ramirez E, Wilson MR, Killion JJ, et al. Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res 1996; 2(9):1627–1636.PubMedGoogle Scholar
  140. 140.
    Chung LWK. Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implications. Cancer 2003; 97(Suppl. 3):772–778.PubMedCrossRefGoogle Scholar
  141. 141.
    Nelson JB, Carducci MA. The role of endothelin-1 and endothelin receptor antiagonists in prostate cancer. BJU Int. 2000; 85(Suppl 2):45–48.PubMedCrossRefGoogle Scholar
  142. 142.
    Hobisch A, Eder IE, Putz T, Horninger W, Bartsch G, Klocker H, et al. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 1998; 58:4640–4645.PubMedGoogle Scholar
  143. 143.
    Blaszczyk N, Masri BA, Mawji NR, Ueda T, McAlinden G, Duncan CP, et al. Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. Clin Cancer Res 2004; 10(5):1860–1869.PubMedCrossRefGoogle Scholar
  144. 144.
    Leaf AN, Propert K, Corcoran C, Catalano PJ, Trump DL, Harris JE, et al. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. Med Oncol 2003; 20(2):137–146.PubMedCrossRefGoogle Scholar
  145. 145.
    Small EJ, Bok R, Reese DM, Sudilovsky D, Frohlich M. Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer. Semin Oncol 2001; 28(4 Suppl 15):71–76.PubMedCrossRefGoogle Scholar
  146. 146.
    Hudes G, Einhorn L, Ross E, Balsham A, Loehrer P, Ramsey H, et al. Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: a Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol 1999; 17(10):3160–3166.PubMedGoogle Scholar
  147. 147.
    Saxman S, Ansarai R, Drasga R, et al. Phase III trial of cyclophosphamide versus cyclophosphamide, doxorubicin, and methotrexate in hormone-refractory prostatic cancer. A Hoosier Oncology Group study. Cancer 1992; 70: 2488–2492.PubMedCrossRefGoogle Scholar
  148. 148.
    Hussain M, Petrylak D, Fisher E, Tangen C, Crawford D. Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Semin Oncol 1999; 26(5 Suppl 17):55–60.PubMedGoogle Scholar
  149. 149.
    Chi KN, Murray RN, Gleave ME, Kuhn J, Izbicka E, Berg K, et al. A phase II study of oblimersen sodium (G3139) and docetaxel (D) in patients (pts) with metastatic hormone-refractory prostate cancer (HRPC). Proc Am Soc Clin Oncol 2001; 22:393 (abstract no. 1580).Google Scholar
  150. 150.
    Beer TM, Hough KM, Garzotto M, Pierce WC, Lowe BA, Henner D. Treatment of Androgen-Independent Prostate Cancer with Weekly High-Dose Calcitriol and Docetaxel. Proc Am Soc Clin Oncol 2001 (abstract no. 2369).Google Scholar
  151. 151.
    Gleave M, Nelson C, Chi K. Antisense targets to enhance hormone and cytotoxic therapies in advanced prostate cancer. Curr Drug Targets 2003; 4(3):209–221.PubMedCrossRefGoogle Scholar
  152. 152.
    Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, et al. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1expression in prostate cancers. Am J Pathol 1996; 148(5):1567–1576.PubMedGoogle Scholar
  153. 153.
    Bubendorf L, Sauter G, Moch H, Jordan P, Blochlinger A, Gasser TC, et al. Am J Pathol 1996; 148(5):1557–1565.PubMedGoogle Scholar
  154. 154.
    Raffo AJ, Perlman H, Chen MW, Day ML, Steitman JS, Buttyan R. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 1995; 55(19):4438–4445.PubMedGoogle Scholar
  155. 155.
    Stattin P, Damber JE, Karlberg L, Nordgren H, Bergh A. Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival. Urol Res 1996; 24(5):257–264.PubMedCrossRefGoogle Scholar
  156. 156.
    McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsiesh JT, et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992; 52(24):6940–6944.PubMedGoogle Scholar
  157. 157.
    Colombel M, Symmans F, Gil S, O’Toole KM, Chopin D, Benson M, et al. Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. Am J Pathol 1993; 143(2):390–400.PubMedGoogle Scholar
  158. 158.
    Rosser CJ, Reyes A O, Vakar-Lopez F, Levy LB, Kuban DA, Hoover DC, et al. Bcl-2 is significantly overexpressed in localized radio-recurrent prostate carcinoma, compared with localized radio-naïve prostate carcinoma. Int J Radiation Oncol Biol Phys 2003; 56(1):1–6.CrossRefGoogle Scholar
  159. 159.
    Pollack A, Cowen D, Troncoso P, Zagars GK, von Eschenbach AC, Meistrich ML, et al. Molecular markers of outcome after radiotherapy in patients with prostate carcinoma: Ki-67, bcl-2, bax, and bcl-x. Cancer 2003; 97(1):1630–1638.PubMedCrossRefGoogle Scholar
  160. 160.
    Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Srivastava S, Moul JW. Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol 1996; 156(4):1511–1516.PubMedCrossRefGoogle Scholar
  161. 161.
    Gleave M, Tolcher A, Miyake H, Nelson C, Brown B, Beraldi E, Goldie J. Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model. Clin Cancer Res 1999; 5(10): 2891–2898.PubMedGoogle Scholar
  162. 162.
    Miayake H, Tolcher A, Gleave ME. Chemosensitization and delayed androgen-independent recurrence of prostate cancer with the use of antisense Bcl-2 oligodeoxynucleotides. J Natl Cancer Inst 2000; 92(1):34–41.PubMedCrossRefGoogle Scholar
  163. 163.
    Tolcher AW. Preliminary phase I results of G3139 (bcl-2 antisense oligonucleotide) therapy in combination with docetaxel in hormone-refractory prostate cancer. Semin Oncol 2001; 28(4 Suppl 15):67–70.PubMedCrossRefGoogle Scholar
  164. 164.
    Chi KN, Gleave ME, Klasa R, Murray N, Bryce C, Lopes de Menezes, DE, et al. A phase I dosefinding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer. Clin Cancer Res 2001; 7(12):3920–3927.PubMedGoogle Scholar
  165. 165.
    Steinberg J, Oyasu R, Lang S, Sintich S, Rademaker A, Lee C, et al. Intracellular levels of SGP-2 (clusterin) correlate with tumor grade in prostate cancer. Clin Cancer Res 1997; 3:1807–1811Google Scholar
  166. 166.
    Gleave ME, Zellweger T, Chi K, Miyake H, Kiyama S, July L, et al. Targeting anti-apoptotic genes upregulated by androgen withdrawal using antisense oligonucleotides to enhance androgen-and chemo-sensitivity in prostate cancer. Invest New Drugs 2002; 20(2):145–158.PubMedCrossRefGoogle Scholar
  167. 167.
    Gleave M, Miyake H, Zangemeister-Wittke U, Jansen B. Antisense therapy: current status in prostate cancer and other malignancies. Cancer Metastasis Rev 2002; 21(1):79–92.PubMedCrossRefGoogle Scholar
  168. 168.
    Jenne DE, Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci 1992; 17(4):154–159.PubMedCrossRefGoogle Scholar
  169. 169.
    Sensibar JA, Sutkowski DM, Raffo A, Buttyan R, Griswold MD, Sylvester SR, et al. Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res 1995; 55:2431–2437.PubMedGoogle Scholar
  170. 170.
    Zhou W, Janulis L, Park II, Lee C. A novel anti-proliferative property of clusterin in prostate cancer cells. Life Sci 2002; 72(1):11–21.PubMedCrossRefGoogle Scholar
  171. 171.
    Bettuzzi S, Hiipakka RA, Gilna P, Liao ST. Identification of an androgen-repressed mRNA ventral prostate as coding for mulphated glycoprotein 2 by cDNA cloning and sequence analysis. Biochem J 1989; 257: 293–296.PubMedGoogle Scholar
  172. 172.
    Scaltriti M, Brausi M, Amorosi A, Caporali A, D’Arca D, Astancolle S, et al. Clusterin (SGP-2, ApoJ) expression is downregulated in low-and high-grade human prostate cancer. Int J Cancer 2004; 108: 23–30.PubMedCrossRefGoogle Scholar
  173. 173.
    Miyake H, Nelson C. Rennie PS, Gleave ME. Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen-independence in prostate cancer. Cancer Res 2000; 60(1): 170–176.PubMedGoogle Scholar
  174. 174.
    Gleave ME, Miyake H, Zellweger T, Chi K, July L, Nelson C, et al. Use of antisense oligonucleotides targeting the antiapoptotic gene, clusterin/testosterone-repressed prostate message 2, to enhance androgen sensitivity and chemosensitivity in prostate cancer. Urology 2001; 58(2 Suppl 1):39–49.PubMedCrossRefGoogle Scholar
  175. 175.
    Miyake H, Nelson C, Rennie PS, Gleave ME. Acquisition of chemoresistant phenotype by overexpression of the antiapoptotic gene testosterone-repressed prostate message-2 in prostate cancer xenograft models. Cancer Res 2000; 60(9):2547–2554.PubMedGoogle Scholar
  176. 176.
    Zellweger T, Miyake H, July LV, Akbari M, Kiyama S, Gleave ME. Chemosensitization of human renal cell cancer using antisense oligonucleotides targeting the antiapoptotic gene clusterin. Neoplasia 2001; 3(4): 360–367.PubMedCrossRefGoogle Scholar
  177. 177.
    Zellweger T, Kiyama S, Chi K, Miyake H, Adomat H, Skov K, et al. Overexpression of the cytoprotective protein clusterin decreases radiosensitivity in the human LNCaP prostate tumour model. BJU Int 2003; 92(4):463–469.PubMedCrossRefGoogle Scholar
  178. 178.
    July LV, Beraldi E, So AI, Evans K, English J, Fazli L, Gleave ME. Nucleotide-based therapies targeting clusterin chemosensitizes human lung adenocarcinoma cells both in vitro and in vivo. Molec Cancer Ther 2004; 3:223–232.Google Scholar
  179. 179.
    Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 2002; 63(4):317–332.PubMedCrossRefGoogle Scholar
  180. 180.
    Moore MG, Wetterau LA, Francis MJ, Peehl DM, Cohen P. Novel stimulatory role for insulin-like growth factor binding protein-2 in prostate cancer cells. Int J Cancer 2003; 105(1):14–19.PubMedCrossRefGoogle Scholar
  181. 181.
    Kiyama S, Morrison K, Zellweger T, Akbari M, Cox M, Yu D, et al. Castration-induced increases in insulinlike growth factor-binding protein-2 promotes proliferation of androgen-independent human prostate LNCaP tumors. Cancer Res 2003; 63:3575–3584.PubMedGoogle Scholar
  182. 182.
    Yu H, Nicar MR, Shi R, Berkel HJ, Nam R, Trachtenberg J, et al. Levels of insulin-like growth factor (IGF-1) and IGF binding proteins 2 and 3 in serial postoperative serum samples and riskof prostate cancer recurrence. Urology 2001; 57(3):471–475.PubMedCrossRefGoogle Scholar
  183. 183.
    Mita K, Nakahara M, Usui T. Expression of the insulin-like growth factor system and cancer progression in hormone-treated prostate cancer patients. Int J Urology 2000; 7(9):321–329.CrossRefGoogle Scholar
  184. 184.
    Shariat SF, Lamb DJ, Kattan MW, Nguyen C, Kim J, Beck J, et al. Association of preoperative plasma levels of insulin-like growth factor I and insulin-like growth factor binding proteins-2 and-3 with prostate cancer invasion, progression, and metastasis. J Clin Oncol 2002; 20(3):833–841.PubMedCrossRefGoogle Scholar
  185. 185.
    Gleave M, Jansen B. Clusterin and IGFBPs as antisense targets in prostate cancer. Ann NY Acad Sci 2003; 1002:95–104.PubMedCrossRefGoogle Scholar
  186. 186.
    Sweeney P, Karashima T, Kim SJ, Kedar D, Mian B, Huang S, et al. Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9 production. Clin Cancer Res 2002; 8:2714–2724.PubMedGoogle Scholar
  187. 187.
    Woelfle U, Cloos J, Sauter G, Riethdorf L, Janicke F, van Diest P, et al. Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res 2003; 63(18):5679–5684.PubMedGoogle Scholar
  188. 188.
    Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003; 3(6):537–549.PubMedCrossRefGoogle Scholar
  189. 189.
    Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP. Molecular Mechanisms of Cancer Pain. Nature Rev Cancer 2002; 2:201–209.CrossRefGoogle Scholar
  190. 190.
    Body JJ, Mancini I. Bisphosphonates for cancer patients: why, how, and when? Support Care Cancer 2002; 10(5):399–407.PubMedCrossRefGoogle Scholar
  191. 191.
    Saad F, Schulman CC. Role of bisphosphonates in prostate cancer. Eur Urol 2004; 45:26–34.PubMedCrossRefGoogle Scholar
  192. 192.
    Stepensky D, Kleinberg L, Hoffman A. Bone as an effect compartment: models for uptake and release of drugs. Clin Pharmacokinet 2003; 42(10):863–881.PubMedCrossRefGoogle Scholar
  193. 193.
    Tsushima N, Yabuki M, Harada H, Katsumata T, Kanamaru H, Nakatsuka I, et al. Tissue distribution and pharmacological potential of SM-16896, a novel oestrogen-bisphosphonate hybrid compound. J Pharm Pharmacol 2000; 52:27–37PubMedCrossRefGoogle Scholar
  194. 194.
    Hirabayashi H, Fujisaki J. Bone-specific drug delivery systems: approaches via chemical modification of bone-seeking agents. Clin Pharmacokinet 2003; 42:1319–1330.PubMedCrossRefGoogle Scholar
  195. 195.
    Wang Y, Metcalf CA 3rd, Shakespeare WC, Sundaramoorthi R, Keenan TP, Bohacek RS, et al. Bone-targeted 2,6,9-trisubstituted purines: novel inhibitors of Src tyrosine kinase for the treatment of bone diseases. Bioorg Med Chem Lett 2003; 13:3067–3070.PubMedCrossRefGoogle Scholar
  196. 196.
    Cooper CR, McLean L, Walsh M, Taylor J, Hayasaka S, Bhatia J, et al. Preferential adhesion of prostate cancer cells to bone is mediated by binding to bone marrow endothelial cells as compared to extracellular matrix components in vitro. Clin Cancer Res 2000; 6:4839–4847.PubMedGoogle Scholar
  197. 197.
    Nemeth JA, Roberts JW, Mullins CM, Cher ML. Persistence of human vascular endothelium in experimental human prostate cancer bone tumors. Clin Exp Metastasis 2000; 18:231–237.PubMedCrossRefGoogle Scholar
  198. 198.
    Illum L, Davis SS. Targeting of colloidal particles to the bone marrow. Life Sci 1987; 40: 1553–1560.PubMedCrossRefGoogle Scholar
  199. 199.
    Gibaud S, Andreux JP, Weingarten C, Renard M, Couvreur P. Increased bone marrow toxicity of doxorubicin bound to nanoparticles. Eur J Cancer 1994; 30A(6):820–826.PubMedCrossRefGoogle Scholar
  200. 200.
    Gibaud S, Demoy M, Andreux JP, Weingarten C, Gouritin B, Couvreur P. Cells involved in the capture of nanoparticles in hematopoietic organs. J Pharm Sci 1996; 85(9):944–950.PubMedCrossRefGoogle Scholar
  201. 201.
    Gibaud S, Weingarten C, Andreux JP, Couvreur P. Targeting bone marrow with the help of polyalkylcyanoacrylate nanoparticles. Ann Pharm Fr 1999; 57(4):324–231.PubMedGoogle Scholar
  202. 202.
    Bally MB, Nayar R, Masin D, Cullis PR, Mayer LD. Studies on the Myelosuppressive Activity of Doxorubicin Entrapped in Liposomes. Cancer Chemother Pharmacol 1990; 27:13–19.PubMedCrossRefGoogle Scholar
  203. 203.
    Gibaud S, Rousseau C, Weingarten C, Favier R, Douay L, Andreux JP, et al. Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF). J Control Release 1998; 52(1–2):131–139.PubMedCrossRefGoogle Scholar
  204. 204.
    Shadyro OI, Yurkova IL, Kisel MA. Radiation-induced peroxidation and fragmentation of lipids in a model membrane. Int J Radiat Biol 2002; 78(3):211–217.PubMedCrossRefGoogle Scholar
  205. 205.
    Marathe D, Mishra KP. Radiation-induced changes in permeability in unilamellar phospholipid liposomes. Radiat Res 2002; 157(6):685–692.PubMedCrossRefGoogle Scholar
  206. 206.
    Symon Z, Peyser A, Tzemach D, Lyass O, Sucher E, Shezen E, et al. Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes. Cancer 1999; 86(1):72–78.PubMedCrossRefGoogle Scholar
  207. 207.
    Guan WY, Yi WT, Zhi MY, Zhen SS. Experimental research on the use of an antineoplastic drug with a bone implant. Int Orthop 1990; 14(4):387–391.PubMedCrossRefGoogle Scholar
  208. 208.
    Katagiri H, Sato K, Takahashi M, Sugiura H, Yamamura S, Iwata H. Use of adriamycin-impregnated methylmethacrylate in the treatment of tumor metastases in the long bones. Arch Orthop Trauma Surg 1997; 116(6-7):329–333.PubMedGoogle Scholar
  209. 209.
    Lebugle A, Rodrigues A, Bonnevialle P, Voigt JJ, Canal P, Rodriguez F. Study of implantable calcium phosphate systems for the slow release of methotrexate. Biomaterials 2002; 23(16):3517–3522.PubMedCrossRefGoogle Scholar
  210. 210.
    Froschle G, Zieron JO, Carl UM, Beck-Bornholdt HP. Combined modality treatment of bone metastases: response of the rhabdomyosarcoma R1H of the rat to postoperative irradiation combined with local release of daunorubicin from acrylic cement. Radiother Oncol 1998; 46(3):317–320.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Ellen K. Wasan
    • 1
  • Martin Gleave
    • 2
  • Karen Fang
    • 3
  • Kim Chi
    • 4
  • Gwyn Bebb
    • 5
  • Lincoln Edwards
    • 3
  • Marcel B. Bally
    • 3
  1. 1.Department of Advanced TherapeuticsBritish Columbia Cancer Research CentreVancouverCanada
  2. 2.Vancouver General Hospital, Prostate CentreVancouverCanada
  3. 3.Department of Pathology and Laboratory MedicineUniversity of British Columbia and British Columbia Cancer Research CentreVancouverCanada
  4. 4.Department of Advanced Therapeutics and Systemic Therapy ProgramBritish Columbia Cancer AgencyCanada
  5. 5.Department of Medical Oncology and British Columbia Cancer Research CentreBritish Columbia Cancer AgencyVancouverCanada

Personalised recommendations