Advertisement

Novel Therapies for Renal Cell Cancer

  • Mayer N. Fishman

Abstract

The discovery of diverse details of the genetics, cell biology, and pathology of disease and the extensive infrastructure for synthesis and testing of targeted drugs or immune strategies are a basis to be hopeful that innovative, effective, widely applicable therapies can be realized for metastatic kidney cancer. High-dose interleukin-2 had been the sole medical therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic renal cancer, and interferon-a, also in widespread use, has had approval in Europe. More than 100 published single-arm/single-drug kidney cancer trials, many based on sound preclinical hypotheses, would seem to be a basis for pessimism. Partial response and disease stabilization at high frequency led to the approval of sorafenib and sunitinib. Whereas progress in conventional cytotoxics has largely bypassed renal cancer, and immune therapies have had dramatic success limited to a minority of patients, some therapies may turn out to be broadly tolerated and efficacious. This is an era for optimism for the application of new technology to kidney cancer therapy.

Keywords

Renal Cell Carcinoma Clin Oncol Renal Cancer Renal Cell Cancer Kidney Cancer 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Amato RJ. Chemotherapy for renal cell carcinoma. Semin Oncol 2000;27(2):177–16.PubMedGoogle Scholar
  2. 2.
    Fishman M, Antonia S. Novel therapies for renal cell carcinoma—an update. Expert Opin Investig Drugs 2003;12(4):593–609.PubMedCrossRefGoogle Scholar
  3. 3.
    Rini BL, Vogezang NJ, Dumas MC, Wade JL, Taber DA, Stadlet WM. Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol 2000;18(12):2419–2426.PubMedGoogle Scholar
  4. 4.
    Ryan CW, Vogezang NJ, Stadler WM. A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma. Cancer 2002;94(10):2602–2609.PubMedCrossRefGoogle Scholar
  5. 5.
    Desai AA, Vogezang NJ, Rini B, et al. A phase II trial of weekly intravenous gemcitabine (G) with prolonged continuous infusion 5-fluorouracil (F) and oral thalidomide (T) in patients with metastatic renal cell cancer (mRCC). Proc Am Soc Clin Oncol 2001;(abstr 2448).Google Scholar
  6. 6.
    George CM, Vogezang NJ, Rini BI, et al. A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma. Ann Oncol 2002;13(1):116–120.PubMedCrossRefGoogle Scholar
  7. 7.
    Waters JS, Moss C, Hackett S, et al. A phase II trial of gemcitabine (GEM) plus capecitabine (CAPE) in patients with metastatic renal cell carcinoma (MRCC). Proc Am Soc Clin Oncol 2003;22:386 (abstr 1549).Google Scholar
  8. 8.
    Stadler WM, Halabi S, Ernstoff MS, et al. A phase II study of gemcitabine (G) and capecitabine (C) in patients with metastatic renal cell cancer (mRCC): a report of Cancer and Leukemia Group B #90008. Proc Am Soc Clin Oncol 2004;23:(abstr 4515).Google Scholar
  9. 9.
    Wenzel C, Locker GJ, Bartsch R, et al. Capecitabine monotherapy and in combination with immunotherapy in the treatment of metastatic renal cell carcinoma. Anticancer Drugs 2003;14(10):779–784.PubMedCrossRefGoogle Scholar
  10. 10.
    Chang DZ, Olencki T, Budd GT, et al. Phase I trial of capecitabine in combination with interferon alpha in patients with metastatic renal cancer: toxicity and pharmacokinetics. Cancer Chemother Pharmacol 2001;48(6):493–498.PubMedCrossRefGoogle Scholar
  11. 11.
    Wenzel C, Locker GJ, Schmidinger M, et al. Capecitabine in the treatment of metastatic renal cell carcinoma failing immunotherapy. Am J Kidney Dis 2002;39(1):48–54.PubMedGoogle Scholar
  12. 12.
    Cheville JC, Lohse CM, Zincke H, et al. Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol 2004;28(4):435–441.PubMedCrossRefGoogle Scholar
  13. 13.
    Townsley CA, Chi K, Ernst DS, et al. Phase II study of troxacitabine (BCH-4556) in patients with advanced and/or metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol 2003;21(8):1524–1529.PubMedCrossRefGoogle Scholar
  14. 14.
    Pyrhonen S, Salminen E, Ruutu M, et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 1999;17:2859–2867.PubMedGoogle Scholar
  15. 15.
    Mertens WC, Eisenhauer EA, Jolivet J, Ernst S, Moore M, Muldal A. Docetaxel in advanced renal carcinoma. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 1994;5(2):185–187.PubMedGoogle Scholar
  16. 16.
    Bruntsch U, Heinrich B, Kaye SB, et al. Docetaxel (Taxotere) in advanced renal cell cancer. A phase II trial of the EORTC Early Clinical Trials Group. Eur J Cancer 1994;30A(8):1064–1067.PubMedCrossRefGoogle Scholar
  17. 17.
    Sternberg J, Berry M, Gregurich M, Boxer M, Anthony S. Phase-II trial of single-agent, weekly docetaxel in advanced or metastatic renal cell carcinoma (MRCC). Proc Am Soc Clin Oncol 2001;(abstr 2379).Google Scholar
  18. 18.
    Ojima I, Chakravarty S, Inoue T, et al. A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc Natl Acad Sci USA 1999;96(8):4256–4261.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhuang SH, Menefee M, Kotz H, et al. A phase II clinical trial of BMS-247550 (ixabepilone), a microtubule-stabilizing agent in renal cell cancer. Proc Am Soc Clin Oncol 2004;(abstr 4550).Google Scholar
  20. 20.
    Brauch H, Weirich G, Brieger J, et al. VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Cancer Res 2000;60(7):1942–1948.PubMedGoogle Scholar
  21. 21.
    Tan C, Roecker AJ, Noronha R, et al. Identification of a small molecule inhibitor of hypoxia-inducible factor (HIF) pathway. American Association for Cancer Research, (AACR) 2004;(abstr 2047).Google Scholar
  22. 22.
    Kline ER, Feng Y, Pribluda V, Lavallee T, Giannakakou P. Translational inhibition of HIF-1a by 2ME2. AACR 2004;(abstr 5428).Google Scholar
  23. 23.
    Drucker B, Bacik J, Ginsberg M, et al. Phase II trial of ZD1839 (IRESSA) in patients with advanced renal cell carcinoma. Invest New Drugs 2003;21(3):341–345.PubMedCrossRefGoogle Scholar
  24. 24.
    Dawson NA, Guo C, Zak R, et al. A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma. Proc Am Soc Clin Oncol 2003;22:404(abstr 1623).Google Scholar
  25. 25.
    Hainsworth JD, Sosman JA, Spigel DR, et al. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol 2005;23:7889–7896.PubMedCrossRefGoogle Scholar
  26. 26.
    Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:16–24.PubMedCrossRefGoogle Scholar
  27. 27.
    Davis NB, Taber DA, Ansari RH, et al. Phase II trial of PS-341 in patients with renal cell cancer: a University of Chicago Phase II Consortium Study. J Clin Oncol 2004;1:115–119.Google Scholar
  28. 28.
    Drucker BJ, Schwartz L, Bacik J, Mazumdar M, Marion S, Motzer RJ. Phase II trial of PS-341 shows response in patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol 2003;22:386(abstr 1550).Google Scholar
  29. 29.
    Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004;22(5):909–918.PubMedCrossRefGoogle Scholar
  30. 30.
    Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prog-nostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17(8):2530.PubMedGoogle Scholar
  31. 31.
    Smith JW, Ko Y-J, Dutcher J, et al. Update of a phase 1 study of intravenous CCI-779 given in combination with interferon to patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol 2004;(abstr 385).Google Scholar
  32. 32.
    Ratain MJ, Flaherty KT, Stadler WM, et al. Preliminary antitumor activity of BAY 43-9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trial (RDT). Proc Am Soc Clin Oncol 2004;(abstr 382).Google Scholar
  33. 33.
    Beeram M, Patnaik A, Rowinsky EK. Raf: A strategic target for therapeutic development against cancer. J Clin Oncol 2005;23:6771–6790.PubMedCrossRefGoogle Scholar
  34. 34.
    Escudier B. Randomized phase III trial of the multi-kinase inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma. Abstract # 794. 11/3/2005. ECCO XIII conference (Paris).Google Scholar
  35. 35.
    Wigginton JM, Komschlies KL, Back TC. Administration of interleukin 12 with pulse interleukin 2 and the rapid and complete eradication of murine renal carcinoma. J Natl Cancer Inst 1996;88:38–43.PubMedCrossRefGoogle Scholar
  36. 36.
    Alatrash G, Hutson TE, Molto L, et al. Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J Clin Oncol 2004;22(14):2891–2900.PubMedCrossRefGoogle Scholar
  37. 37.
    Kwon ED, Foster BA, Hurwitz AA, et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc Natl Acad Sci USA 1999;96(26):15074–15079.PubMedCrossRefGoogle Scholar
  38. 38.
    Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996;271(5256):1734–1736.PubMedCrossRefGoogle Scholar
  39. 39.
    Hodi FS, Mihm MC, Soiffer RJ, et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA 2003;100(8):4712–4717.PubMedCrossRefGoogle Scholar
  40. 40.
    Escudier B, Lassau N, Couanet D, et al. Phase II trial of thalidomide in renal-cell carcinoma. Ann Oncol 2002;13(7):1029–1035.PubMedCrossRefGoogle Scholar
  41. 41.
    Motzer RJ, Berg W, Ginsberg M, et al. Phase II trial of thalidomide for patients with advanced renal cell carcinoma. J Clin Oncol 2002;20(1):302–306.PubMedCrossRefGoogle Scholar
  42. 42.
    Stebbing J, Benson C, Eisen T, et al. The treatment of advanced renal cell cancer with high-dose oral thalidomide. Br J Cancer 2001;85(7):953–958.PubMedCrossRefGoogle Scholar
  43. 43.
    Eisen T, Boshoff C, Mak I, et al. Continuous low dose thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 2000;82(4):812–817.PubMedCrossRefGoogle Scholar
  44. 44.
    Daliani DD, Papandreou CN, Thall PF, et al. A pilot study of thalidomide in patients with progressive metastatic renal cell carcinoma. Cancer 2002;95(4):758–765.PubMedCrossRefGoogle Scholar
  45. 45.
    Amato R, Breheny S, Tracy E. Phase I/II study of thalidomide + interleukin II (IL-2) for patients with metastatic renal cell carcinoma. Proc Am Soc Clin Oncol 2002;(abstr 759).Google Scholar
  46. 46.
    Rawat A, Amato RJ. Phase II Study of thalidomide, interleukin-2 (IL-2), and granulocyte macrophage-colony stimulating factor (GMCSF) in patients with metastatic renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 2004;(abstr 431).Google Scholar
  47. 47.
    Olencki T, Dreicer R, Elson P, Wood L, Bukowski R. Phase I trial of thalidomide and interleukin-2 (IL-2) in patients (pts) with metastatic renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 2002;(abstr 2430).Google Scholar
  48. 48.
    Chapa P, Rawat A, Amato RJ. Phase II study of CC-5013 in patients (pts) with renal cell cancer (RCC). Proc Am Soc Clin Oncol 2004;(abstr 4761).Google Scholar
  49. 49.
    Gordon MS, Manola J, Fairclough D, et al. Low dose interferon-a2b (IFN) + thalidomide (T) in patients (pts) with previously untreated renal cell cancer (RCC). Improvement in progression-free survival (PFS) but not quality of life (QoL) or overall survival (OS). A phase III study of the Eastern Cooperative Oncology Group (E2898). Proc Am Soc Clin Oncol 2004;(abstr 4516).Google Scholar
  50. 50.
    Prescribing information, Pegasys package insert.Google Scholar
  51. 51.
    Prescribing information, Pegintron package insert.Google Scholar
  52. 52.
    Motzer RJ, Rakhit A, Thompson J, et al. II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma. Ann Oncol 2002;13(11):1799–1805.PubMedCrossRefGoogle Scholar
  53. 53.
    Motzer RJ, Rakhit A, Ginsberg M, et al. Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. J Clin Oncol 2001;19(5):1312–1319.PubMedGoogle Scholar
  54. 54.
    Bukowski R, Ernstoff MS, Gore ME, et al. Pegylated interferon alfa-2b treatment for patients with solid tumors: a phase I/II study. J Clin Oncol 2002;20(18):3841–3849.PubMedCrossRefGoogle Scholar
  55. 55.
    Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 1993;85(8):622–632.PubMedCrossRefGoogle Scholar
  56. 56.
    Law TM, Motzer RJ, Mazumdar M, et al. Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer 1995;76(5):824–832.PubMedCrossRefGoogle Scholar
  57. 57.
    Figlin RA, Thompson JA, Bukowski RM, et al. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol 1999;17(8):2521–2529.PubMedGoogle Scholar
  58. 58.
    http://www.nci.nih.gov/search/clinical_trials/ (Search kidney cancer: STLMC-BRM-9401, NCI-V94-0514; John Hanson, P.I.).Google Scholar
  59. 59.
    Su Z, Dannull J, Heiser A, et al. Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 2003;63(9):2127–2133.PubMedGoogle Scholar
  60. 60.
    Hirschowitz EA, Foody T, Kryscio R, Dickson L, Sturgill J, Yannelli J. Autologous dendritic cell vaccines for non-small-cell lung cancer. J Clin Oncol 2004;22(14):2808–2815.PubMedCrossRefGoogle Scholar
  61. 61.
    Avigan D, Vasir B, Gong J, et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res 2004;10(14):4699–4708.PubMedCrossRefGoogle Scholar
  62. 62.
    Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 2000;343(11):750–758.PubMedCrossRefGoogle Scholar
  63. 63.
    Ueno NT, Cheng YC, Rondon G, et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. Blood 2003;102(10):3829–3836.PubMedCrossRefGoogle Scholar
  64. 64.
    Blaise D, Bay JO, Faucher C, et al. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 2004;103(2):435–441.PubMedCrossRefGoogle Scholar
  65. 65.
    Rini BI, Zimmerman TM, Gajewski TF, Stadler WM, Vogelzang NJ. Allogeneic peripheral blood stem cell transplantation for metastatic renal cell carcinoma. J Urol 2001;165(4):1208–1209.PubMedCrossRefGoogle Scholar
  66. 66.
    Dai J, Liu B, Caudill MM, et al. Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumor-specific T cell memory. Cancer Immunol 2003;3:1.Google Scholar
  67. 67.
    Graner MW, Zeng Y, Feng H, Katsanis E. Tumor-derived chaperonerich cell lysates are effective therapeutic vaccines against a variety of cancers. Cancer Immunol Immunother 2003;52(4):226–234.PubMedGoogle Scholar
  68. 68.
    Mazzaferro V, Coppa J, Carrabba MG, et al. Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res 2003;9(9):3235–3245.PubMedGoogle Scholar
  69. 69.
    http://www.antigenics.com/products/cancer/oncophage/ and http://www.antigenics.com/.Google Scholar
  70. 70.
    Antonia SJ, Seigne J, Diaz J, et al. Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma. J Urol 2002;167(5):1995–2000.PubMedCrossRefGoogle Scholar
  71. 71.
    Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Hum Gene Ther 1999;10(12):1983–1991.PubMedCrossRefGoogle Scholar
  72. 72.
    http://www.gvax.com/home.shtml.Google Scholar
  73. 73.
    Jocham D, Richter A, Hoffmann L, et al. Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet 2004;363(9409):594–599.PubMedCrossRefGoogle Scholar
  74. 74.
    Fishman M, Antonia S. Specific antitumour vaccine for renal cancer. Lancet 2004;363(9409):583–584.PubMedCrossRefGoogle Scholar
  75. 75.
    Folkman J, Kalluri R. Cancer without disease. Nature 2004;427(6977):787.PubMedCrossRefGoogle Scholar
  76. 76.
    Folkman J. Angiogenesis inhibitors: a new class of drugs. Cancer Biol Ther 2003;2(4 suppl 1):S127–133.PubMedGoogle Scholar
  77. 77.
    Nakamura M, Abe Y, Tokunaga T. Pathological significance of vascular endothelial growth factor A isoform expression in human cancer. Pathol Int 2002;52(5–6):331–339.PubMedCrossRefGoogle Scholar
  78. 78.
    Clauss M. Molecular biology of the VEGF and the VEGF receptor family. Semin Thromb Hemost 2000;26(5):561–569.PubMedCrossRefGoogle Scholar
  79. 79.
    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335–2342.PubMedCrossRefGoogle Scholar
  80. 80.
    Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002;99(17):11393–11398.PubMedCrossRefGoogle Scholar
  81. 81.
    Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349(5):427–434.PubMedCrossRefGoogle Scholar
  82. 82.
    Rini BI, Halabi S, Taylor J, Small EJ, Schilsky RL. Cancer and Leukemia Group B 90206: a randomized phase III trial of interferonalpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin Cancer Res 2004;10(8):2584–2586.PubMedCrossRefGoogle Scholar
  83. 83.
    www.oxigene.com.Google Scholar
  84. 84.
    Stevenson JP, Rosen M, Sun W, et al. Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J Clin Oncol 2003;21(23):4428–4438.PubMedCrossRefGoogle Scholar
  85. 85.
    Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004;10(2):415–427.PubMedCrossRefGoogle Scholar
  86. 86.
    Gingras D, Renaud A, Mousseau N, Beaulieu E, Kachra Z, Beliveau R. Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound. Anticancer Res 2001;21(1A):145–155.PubMedGoogle Scholar
  87. 87.
    Beliveau R, Gingras D, Kruger EA, et al. The antiangiogenic agent neovastat (AE-941) inhibits vascular endothelial growth factormediated biological effects. Clin Cancer Res 2002;8(4):1242–1250.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2007

Authors and Affiliations

  • Mayer N. Fishman
    • 1
  1. 1.Genitourinary Oncology & Experimental Therapeutics Department of Interdisciplinary Oncology H. Lee Mofitt Cancer Center and Research InstituteUniversity of South FloridaTampaUSA

Personalised recommendations