Kidney Cancer pp 227-238 | Cite as

Novel Therapies for Renal Cell Carcinoma

  • Samira Syed
  • Anthony W. Tolcher
Part of the Cancer Treatment and Research book series (CTAR, volume 116)

Abstract

The treatment of advanced renal cell carcinoma presents a daunting challenge to medical, surgical and radiation oncologists. Although patients with localized renal cell carcinoma can be effectively treated by surgery with a 5 year survival of up to 88%, the treatment options are limited for patients with advanced disease with the 5 year survival rate under 10%.12Furthermore, systemic chemotherapeutic agents have had little impact on the natural history of this disease. A comprehensive review by Yagodaet at 3 encompassed 4542 patients enrolled in 83 clinical trials published from 1983 through 1993. Among the 4093 evaluable patients, a 6% overall response rate was determined which was comprised of 53 (1.3%) complete responses and 192 (4.7%) partial responses. This dismal level of antitumor activity is comparable to the reported rate of spontaneous objective responses observed for placebo treated patients entered in a randomized study.4

Keywords

Placebo Toxicity Oncol Interferon Doxorubicin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. 1.
    DeVita VT, Hellman S, Rosenberg SA (2001) Cancer Principles and Practice of Oncology, 6thEdition. pp 1362–1394.Google Scholar
  2. 2.
    Cancer Facts and Figures2002: Surveillance, Epidemiology and End Results Program (1973–1998). Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda.Google Scholar
  3. 3.
    Yagoda A, Abi-Bached B, Petrylak D (1995) Chemotherapy for advanced renal cell carcinoma: 1983–1993. Semin Oncol 22: 42.PubMedGoogle Scholar
  4. 4.
    Gleave ME, Elhilali M, Fradet Y, et al (1998) Interferon Gamma-1 b compared with placebo in metastatic renal cell carcinoma. N Engl J Med 338: 1265–1271.PubMedCrossRefGoogle Scholar
  5. 5.
    Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186.PubMedCrossRefGoogle Scholar
  6. 6.
    Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Nat Cancer Inst 82: 4–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Ellis LM (2002) Angiogenesis. Horizons in cancer therapeutics. 3: 4–22.Google Scholar
  8. 8.
    Gerber HP, Dixit V, Ferrara N (1998) Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and Al in vascular endothelial cells. J Biol Chem 273: 13313–13316.PubMedCrossRefGoogle Scholar
  9. 9.
    Gerber HP, McMurtrey A, Kowalski J, et al (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. J Biol Chem 273: 30336–30343.PubMedCrossRefGoogle Scholar
  10. 10.
    Eliceiri BP, Cheresh DA (1999) The role of alpha v integrins during angiogenesis: insights into potential mechanisms of action and clinical development. JClin Invest 103: 1227–1230.CrossRefGoogle Scholar
  11. 11.
    Scatena M, Ahneida M, Chaisson ML, et al (1998) NF-Kappa B mediates alpha v beta 3 integrininduced endothelial cell survival. J Cell Biol 141: 1083–1093.PubMedCrossRefGoogle Scholar
  12. 12.
    Zbar B (1995) Von Hippel-Lindau disease and sporadic renal cell carcinoma. Cancer Surveys 25: 219–232.PubMedGoogle Scholar
  13. 13.
    Clifford SC, Astuti D, Hooper L, et al (2001) The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx 1 and HIF-1 alpha in renal cell carcinoma. Oncogene 20: 5067–5074.PubMedCrossRefGoogle Scholar
  14. 14.
    Takahashi A, Sasaki H, Kim SJ, et al (1994) Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 54: 4233–4237.PubMedGoogle Scholar
  15. 15.
    Baccala AA, Zhong H, Clift SM, et al (1998) Serum vascular endothelial growth factor is a candidate biomarker of metastatic tumor response to ex vivo gene therapy of renal cell cancer. Urology 51: 327–332.PubMedCrossRefGoogle Scholar
  16. 16.
    Bigelow KR, Spiotto MT, Stadler WM (2001) Anti-angiogenic Agents and Strategies in Renal Cell Carcinoma. Current Clin Oncol pg 381–395.Google Scholar
  17. 17.
    Blay JY, Pallardy M, Ravaud A, et al (1999) Serum VEGF is an independent prognostic factor in patients with metastatic renal carcinoma treated with IL-2 and/or interferon:Analysis of the CRECY trial. Proc Am Soc Clin Oncol. 18: 433a; A1669.Google Scholar
  18. 18.
    Nanus DM, Schmitz-Drager BJ, Motzer RJ, et al (1993) Expression of basic fibroblast growth factor in primary human renal tumors: Correlation with poor survival. J Natl Cancer Inst 85: 1597–1599.PubMedCrossRefGoogle Scholar
  19. 19.
    Asano M, Yukita A, Matsumoto T, et al (1995) Inhibition of tumor growth and metastatses by an immuno-neutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor 121, Cancer Res. 55: 5296–5301.PubMedGoogle Scholar
  20. 20.
    Ferrara N, Houck K, Jakeman L, et al (1992) Molecular and biological properties of the vascular endothelial cell growth factor family of proteins. Endocrine Rev 13: 18–32.Google Scholar
  21. 21.
    Basche M, Sandler AB, Eckhardt SG, et al (2002) Angiozyme, an anti-VEGFRI ribozyme, carboplatin and paclitaxel: results of a phase I study. Proc Am Soc Clin Oncol 21: 112a abst 445.Google Scholar
  22. 22.
    Margolin K, Gordon MS, Holmgren E, et al (2001) Phase lb Trial for Intravenous Recombinant Humanized Monoclonal Antibody to Vascular Endothelial Growth Factor in Combination with Chemotherapy in Patients with Advanced Cancer: Pharmacologic and Long-Term Safety Data. J Clin Oncol 19: 851–856.PubMedGoogle Scholar
  23. 23.
    Gordon MS, Margolin K, Talpaz M, et al (2001) Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19: 843–850.PubMedGoogle Scholar
  24. 24.
    Kabbinavar FF, Wong JT, Ayala RE, et al (1995) The effect of antibody to vascular endothelial growth factor and cisplatin on the growth of lung tumors in nude mice. Proc Am Assoc Cancer Res 36: 488; abst 2906.Google Scholar
  25. 25.
    Borgstrom P, Gold DP, Hilan KJ, et al (1999) Importance of VEGF for breast cancer angiogenesis in vivo: Implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res 19: 4203–4214.PubMedGoogle Scholar
  26. 26.
    Yang JC, Haworth L, Steinberg SM, et al (2002) A randomized double-blind placebo-controlled trial of bevacizmab (anti-VEGF antibody) demonstrating a prolongation in time to progression in patients with metastatic renal cancer. Proc Am Soc Clin Oncol 21: 5a; A15.Google Scholar
  27. 27.
    Strawn LM, Mc Maho G, App H, et al (1996) Flk-1 as a target for tumor growth inhibition. Cancer Res 56: 3540–3545.PubMedGoogle Scholar
  28. 28.
    Fong TA, Shawver LK, Sun L, et al (1999) SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1 /KDR) that inhibits tyrosine kinase catalysis, tumor vascularization and growth of multiple tumor types, Cancer Res 59: 99–106.PubMedGoogle Scholar
  29. 29.
    Rosen L, Mulay M, Mayers A, et al (1999) Phase I dose-escalating trial of SU5416, a novel angiogenesis inhibitor in patients with advanced malignancies. Proc Am Soc Clin Oncol. 18: 161a; A618Google Scholar
  30. 30.
    Cropp G, Rosen L, Mulay M, et al (1999) Pharmacokinetics and pharmacodynamics of SU5416 in a phase I, dose escalating trial in patients with advanced malignancies. Proc Am Soc Cliin Oncol 18: 161a; A619.Google Scholar
  31. 31.
    Stopeck A. (2000) Results of a phase I dose-escalating study of the anti-angiogenic agent, SU5416, in patients with advanced malignancies. Proc Am Soc Clin Oncol 19: 206a; A802.Google Scholar
  32. 32.
    Tolcher A, Karp DD, O’leary DD, et al (2002) A phase I and biologic correlative study of an oral vascular endothelial growth factor receptor-2 (VEGF-2) tyrosine kinase inhibitor, CP 547,632 in patients with advanced malignancies. Proc Am Soc Clin Oncol 21: 84a; A334.Google Scholar
  33. 33.
    Hurwitz H, Holden SN, Eckhardt SG, et al (2002) Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling in patients with solid tumors. Proc Am Soc Clin Oncol 21: 82a; A325.Google Scholar
  34. 34.
    Drevs J, Schmidt-Gersbach IM, Mross K, et al (2002) Surrogate markers for the assessment of biologic activity of the VEGF-receptor inhibitor PTK787/ZK 222584 (PTK/ZK) in two clinical trials. Proc Am Soc Clin Oncol 21: 85a; A337.Google Scholar
  35. 35.
    D’Amato RJ, Loughnan MS, Flynn E, et al (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 91: 4082–4085.PubMedCrossRefGoogle Scholar
  36. 36.
    Rowland TL, McHugh SM, Deighton J, et al (1998) Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology. 40: 11–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Koch HP (1985) Thalidomide and congeners as anti-inflammatory agents. Prog Med Chem. 22: 165–242.PubMedCrossRefGoogle Scholar
  38. 38.
    Stebbing J, Benson C, Eisen T, et al (2001) The treatment of advanced renal cell cancer with high-dose oral thalidomide Br J Cancer 85: 953–958.PubMedCrossRefGoogle Scholar
  39. 39.
    Motzer RJ, Berg W, Ginsberg M, et al (2002) Phase II trial of thalidomide for patients with advanced renal cell carcinoma. J Clin Oncol 20: 302–306.PubMedCrossRefGoogle Scholar
  40. 40.
    Singh RK, Gutman M, Bucvana CD, et al (1995) Interferon alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad Sci USA 92: 4562–4566.PubMedCrossRefGoogle Scholar
  41. 41.
    Berg WI Divgi CR, Nanus DM, et al (2000) Novel Investigative Approaches for Advanced Renal Cell Carcinoma. Semin Oncol 27: 234–239.Google Scholar
  42. 42.
    Ingber D, Fujita T, Kishimoto S, Sudo K, et al (1990) Synthetic analogues of fiunagillin that inhibit angiogenesis and suppress tumor growth. Nature 348: 555–557.PubMedCrossRefGoogle Scholar
  43. 43.
    Stadler WM, Kuzel T, Shapiro C, et al (1999) Multi-Institutional Study of the Angiogenesis Inhibitor TNP-470 in Metastatic Renal Carcinoma. J Clin Oncol 17: 2541–2545.PubMedGoogle Scholar
  44. 44.
    Yanase T, Tamura M, Fujita K, et al (1993) Inhibitory effect of angiogenesis inhibitor TNP-470 On tumor growth and metastases of human cell lines in vitro and in vivo. Cancer Res 53: 2566–2570.PubMedGoogle Scholar
  45. 45.
    Fujioka T, Hasegawa M, Ogiu K, et al (1996) Anti-tumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma. J Urol 155: 1775–1778.PubMedCrossRefGoogle Scholar
  46. 46.
    Morita T, Shinohara N, Tokue A. (1994) Anti-tumor effect of a synthetic analogue of fiunagillin on murine renal carcinoma. Br J Urol 74: 416–421.PubMedCrossRefGoogle Scholar
  47. 47.
    Kohn EC, Reed E, Sarosy G, et al (1996) Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers, Cancer Res 56: 569–573.PubMedGoogle Scholar
  48. 48.
    Kohn EC, Felder CC, Jacobs W, et al (1994) Structure-function analysts of signal and growth inhibition by carboxyamido-triazole, CAI Cancer Res 54: 935–942.Google Scholar
  49. 49.
    Kohn EC, Liotta LA. (1995) Molecular insights into cancer invasion: strategies for prevention and intervention, Cancer Res 55: 1856–1862.PubMedGoogle Scholar
  50. 50.
    Fan Z, Baselga J, Masui H, et al (1993) Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 53: 4637–4642.PubMedGoogle Scholar
  51. 51.
    Masui H, kawamoto T, Sato JD, et al (1984) Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 44: 1002–1007.PubMedGoogle Scholar
  52. 52.
    Prewett M, Rockwell P, Rockwell RF, et al (1996) The biologic effects of C225, a chimeric monoclonal antibody to the EGFR on human prostate carcinoma. j Immunother 19: 419–427.CrossRefGoogle Scholar
  53. 53.
    Kawamoto T, Sato JD, Le A, et al (1983) Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci USA 80: 1337–1341.PubMedCrossRefGoogle Scholar
  54. 54.
    Rowinsky EK (2001) Signal transduction inhibitors. Horizons in cancer therapeutics. 2: 3–35.Google Scholar
  55. 55.
    Mendelsohn J, (2000) Blockade of receptors for growth factors: an anticancer therapy: the fourth annual Joseph H. Burchenal American Association for Cancer Research Clinical Research Clinical Award Lecture. Clin Cancer Res 6: 747–752.PubMedGoogle Scholar
  56. 56.
    Huang SM, Bock JM, Harari PM. (1999) Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radio-sensitivity in squamous cell carcinoma of the head and neck. Cancer Res 59: 1935–1940.PubMedGoogle Scholar
  57. 57.
    Shin DM, Donato NJ, Perez-Soler R, et al (2001) Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 7: 1204–1213.PubMedGoogle Scholar
  58. 58.
    Baselga J, Pfister D, Cooper MR, et al (2000) Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 18: 904–914.PubMedGoogle Scholar
  59. 59.
    Gunnett K, Motzer R, Amato R, et al (1999) Phase II study of anti-epidermal growth factor receptor antibody C225 alone in patients with metastatic renal cell carcinoma. Proc Am Soc Clin Oncol 18: 340a; A1309.Google Scholar
  60. 60.
    Yang XD, Jia XC, Corvalan JR, et al (1999) Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 59: 1236–1243.PubMedGoogle Scholar
  61. 61.
    Figlin RA, Belldegun A, Lohner ME (2001) ABX-EGF: A fully humanized anti-EGF receptor antibody in patients with advanced cancer. Proc Am Soc Clin Oncol 20: 276a; A1102.Google Scholar
  62. 62.
    Schwartz G, Dutcher JP, Vogelzang NJ, et al (2002) Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC) Proc Am Soc Clin Oncol 21: 24a; A91.Google Scholar
  63. 63.
    Woodburn J, Kendrew J, Fennel M (2000) ZD1839 (“Iressa”) a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI): inhibitor of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition. Proc Am Assoc Cancer Res 41: 402; A2552.Google Scholar
  64. 64.
    Ciardiello F, Caputo R, Bianco R, et al (2001) Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 7: 1459–1465.PubMedGoogle Scholar
  65. 65.
    Ranson M, Hammond L, Ferry D, et al (2002) ZD1839 a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid malignant tumors: results of a phase I trial. J Clin Oncol 20: 2240–2250.PubMedCrossRefGoogle Scholar
  66. 66.
    Baselga J, Herbst R, LoRusso P, et al (2000) Continuous administration of ZD1839 (Iressa), a novel oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected tumor types; evidence of activity and good tolerability. Proc Am Soc Clin Oncol 19: 177a; A686.Google Scholar
  67. 67.
    Goss GD, Hirte H, Lorimer I, et al (2001) Final results of the dose escalation phase of a phase I pharmacokinetics, pharmacodynamic and biological activity study of ZD1839: NCIC CTG IND, 122. Proc Am Soc Clin Oncol. 20: 85a; A335.Google Scholar
  68. 68.
    Hammond LA, Figueroa J, Schwartzberg L, et al (2001) Feasibility and pharmacokinetic trial of ZD1839 (Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor, in combination with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol. 20: 137a; A544.Google Scholar
  69. 69.
    Miller VA, Johnson D, Heelan RT, et al (2001) A pilot trial demonstrates the safety of ZD1839 (Iressa), an oral epidermal growth factor receptor tyrosine kinase inhibitor, in combination with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 20: 326a; A1301.Google Scholar
  70. 70.
    Hidalgo M, Siu LL, Nemunaitis J, et al (2001) Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor in patients with advanced solid malignancies. J Clin Oncol 19: 3267–3279.PubMedGoogle Scholar
  71. 71.
    Yamaguchi H, Paranawithana SR, Lee MW, et al (2002) Epothilone B Analogue (BMS-247550)- Mediated Cytotoxicity through Induction of Box Conformational Change in Human Breast Cancer Cells. Cancer Res 62: 466–471.PubMedGoogle Scholar
  72. 72.
    Lee FYF, Borzilleri R, Fairchild CR, et. Al. (2001) BMS-247550: A Novel Epothilone Analog with a Mode of Action Similar to Paclitaxel but Possessing Superior Anti-tumor Efficacy Clin Cancer Res 7: 1429–1437.Google Scholar
  73. 73.
    Hidalgo M, Rowinsky EK. (2000) The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 19: 6680–6686.PubMedCrossRefGoogle Scholar
  74. 74.
    Mills GB, Lu Y, Kohn EC (2001) Linking molecular therapeutics to molecular diagnostics: Inhibition of the FRAP/RAFT/TOR component of the P1 3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo. Proc Natl Acad Sci 98: 10031–10033.PubMedCrossRefGoogle Scholar
  75. 75.
    Atkins MB, Hidalgo M, Stadler W, et al (2002) A randomized double-blind phase 2 study of intravenous CCI-779 administered weekly to patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol. 21: 10a; A36.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Samira Syed
    • 1
  • Anthony W. Tolcher
    • 2
  1. 1.Division of Medical OncologyUniversity of Texas Health Science Center at San AntonioUSA
  2. 2.Associate Director Clinical Research, Institute for Drug Development, Cancer Therapy and Research Center and Associate Clinical Professor of MedicineUniversity of Texas Health Science Center at San AntonioUSA

Personalised recommendations