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Chemotherapy, Targeted Therapies, and Biological Therapies for Renal Cell Carcinoma

  • Farshid Dayyani
  • Eric Jonasch
Reference work entry

Abstract

The last 5 years have seen a major shift in the treatment of patients with advanced renal cell carcinoma. Since 2005, a total of six new agents were approved for use in advanced RCC, including four antiangiogenic agents and two mammalian targets of rapamycin (mTOR) inhibitors. This chapter reviews currently used agents, describes the integration of surgical management and systemic therapy, and summarizes future directions in the systemic management of patients with advanced RCC.

Keywords

Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Advanced Renal Cell Carcinoma Interferon Alfa Cytokine Therapy 
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.

References

  1. 1.
    Motzer RJ, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004;22(3):454–63.CrossRefPubMedGoogle Scholar
  2. 2.
    Mekhail TM, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol. 2005;23(4):832–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Jonasch E, et al. Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(25):4076–81.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cowey CL, et al. Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol. 2010;28(9):1502–7.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rini BI. Metastatic renal cell carcinoma: many treatment options, one patient. J Clin Oncol. 2009;27(19):3225–34.CrossRefPubMedGoogle Scholar
  6. 6.
    Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009;373(9669):1119–32.CrossRefPubMedGoogle Scholar
  7. 7.
    Motzer RJ, et al. Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-α) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). In: ASCO. 2006.Google Scholar
  8. 8.
    Motzer RJ, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–90.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rini BI, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2007;99(1):81–3.CrossRefPubMedGoogle Scholar
  10. 10.
    Rixe O, Billemont B, Izzedine H. Hypertension as a predictive factor of sunitinib activity. Ann Oncol. 2007;18(6):1117.CrossRefPubMedGoogle Scholar
  11. 11.
    Ratain MJ, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24(16):2505–12.CrossRefPubMedGoogle Scholar
  12. 12.
    Escudier B, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Escudier B, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Escudier B, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(8):1280–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Sonpavde G, Hutson TE, Sternberg CN. Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs. 2008;17(2):253–61.CrossRefPubMedGoogle Scholar
  16. 16.
    Sternber CN, Lee E, Salman PV, Mardiak J, Davis D. A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). In ASCO 2009. Orlando; 2009.Google Scholar
  17. 17.
    Rixe O, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007;8(11):975–84.CrossRefPubMedGoogle Scholar
  18. 18.
    Escudier B, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103–11.CrossRefPubMedGoogle Scholar
  19. 19.
    Rini B, Rosenberg J, Stadler WM, Vaena DA, Atkins N, Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: results of overall survival for CALGB 90206. In: ASCO 2009. Orlando; 2009.Google Scholar
  20. 20.
    Escudier BJ, Bracarda S, Melichar B, Delva R, Sevin E, Negrier S. Efficacy and safety of first-line bevacizumab (BEV) plus interferon-α2a (IFN) in subgroups of patients (pts) with metastatic renal cell carcinoma (mRCC). In: ASCO 2009. Orlando; 2009.Google Scholar
  21. 21.
    Hainsworth JD, et al. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol. 2005;23(31):7889–96.CrossRefPubMedGoogle Scholar
  22. 22.
    Bukowski RM, et al. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007;25(29):4536–41.CrossRefPubMedGoogle Scholar
  23. 23.
    Hudes G, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271–81.CrossRefPubMedGoogle Scholar
  24. 24.
    Motzer RJ, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372(9637):449–56.CrossRefPubMedGoogle Scholar
  25. 25.
    Harris DT. Hormonal therapy and chemotherapy of renal-cell carcinoma. Semin Oncol. 1983;10(4):422–30.PubMedGoogle Scholar
  26. 26.
    Yagoda A, Petrylak D, Thompson S. Cytotoxic chemotherapy for advanced renal cell carcinoma. Urol Clin North Am. 1993;20(2):303–21.PubMedGoogle Scholar
  27. 27.
    Casali M, et al. Gemcitabine in pre-treated advanced renal carcinoma: a feasibility study. J Exp Clin Cancer Res. 2001;20(2):195–8.PubMedGoogle Scholar
  28. 28.
    De Mulder PH, et al. Gemcitabine: a phase II study in patients with advanced renal cancer. Cancer Chemother Pharmacol. 1996;37(5):491–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Mertens WC, et al. Gemcitabine in advanced renal cell carcinoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 1993;4(4):331–2.CrossRefPubMedGoogle Scholar
  30. 30.
    Rini BI, et al. Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol. 2000;18(12):2419–26.CrossRefPubMedGoogle Scholar
  31. 31.
    Stadler WM, et al. A phase II study of gemcitabine and capecitabine in metastatic renal cancer: a report of Cancer and Leukemia Group B protocol 90008. Cancer. 2006;107(6):1273–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Tannir NM, et al. A phase II trial of gemcitabine plus capecitabine for metastatic renal cell cancer previously treated with immunotherapy and targeted agents. J Urol. 2008;180(3):867–72. discussion 872.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Gollob JA, et al. Long-term remission in a patient with metastatic collecting duct carcinoma treated with taxol/carboplatin and surgery. Urology. 2001;58(6):1058.CrossRefPubMedGoogle Scholar
  34. 34.
    Nanus DM, et al. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer. 2004;101(7):1545–51.CrossRefPubMedGoogle Scholar
  35. 35.
    Mazumder A, Rosenberg SA. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J Exp Med. 1984;159(2):495–507.CrossRefPubMedGoogle Scholar
  36. 36.
    Fyfe G, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688–96.CrossRefPubMedGoogle Scholar
  37. 37.
    Rosenberg SA, 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):622–32.CrossRefPubMedGoogle Scholar
  38. 38.
    Fisher RI, et al. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med. 1988;108(4):518–23.CrossRefPubMedGoogle Scholar
  39. 39.
    Rosenberg SA, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987;316(15):889–97.CrossRefPubMedGoogle Scholar
  40. 40.
    Fisher RI, et al. High-dose aldesleukin in renal cell carcinoma: long-term survival update. Cancer J Sci Am. 1997;3(Suppl 1):S70–2.PubMedGoogle Scholar
  41. 41.
    Dillman RO, et al. Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial. J Clin Oncol. 1991;9(7):1233–40.CrossRefPubMedGoogle Scholar
  42. 42.
    Weiss GR, et al. A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J Clin Oncol. 1992;10(2):275–81.CrossRefPubMedGoogle Scholar
  43. 43.
    Gold PJ, et al. Metastatic renal cell carcinoma: long-term survival after therapy with high-dose continuous-infusion interleukin-2. Cancer J Sci Am. 1997;3(Suppl 1):S85–91.PubMedGoogle Scholar
  44. 44.
    Sosman JA, et al. Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin. J Natl Cancer Inst. 1988;80(18):1451–61.CrossRefPubMedGoogle Scholar
  45. 45.
    Atkins MB, et al. Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol. 1993;11(4):661–70.CrossRefPubMedGoogle Scholar
  46. 46.
    Dutcher JP, et al. Interleukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group experience, 1989–1997. Cancer J Sci Am. 1997;3(Suppl 1):S73–8.PubMedGoogle Scholar
  47. 47.
    Dutcher JP, et al. Outpatient subcutaneous interleukin-2 and interferon-alpha for metastatic renal cell cancer: five-year follow-up of the Cytokine Working Group Study. Cancer J Sci Am. 1997;3(3):157–62.PubMedGoogle Scholar
  48. 48.
    Rosenberg SA, et al. Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol. 1989;7(12):1863–74.CrossRefPubMedGoogle Scholar
  49. 49.
    Figlin RA, et al. Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2A: an active outpatient regimen in metastatic renal cell carcinoma. J Clin Oncol. 1992;10(3):414–21.CrossRefPubMedGoogle Scholar
  50. 50.
    Atzpodien J, et al. Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol. 1995;13(2):497–501.CrossRefPubMedGoogle Scholar
  51. 51.
    Negrier S, et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d’Immunotherapie. N Engl J Med. 1998;338(18):1272–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Yang JC, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003;21(16):3127–32.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Ko JS, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15(6):2148–57.CrossRefPubMedGoogle Scholar
  54. 54.
    Ko JS, et al. Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res. 2010;70(9):3526–36.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Finke JH, et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res. 2008;14(20):6674–82.CrossRefPubMedGoogle Scholar
  56. 56.
    Gu Y, et al. Sunitinib impairs the proliferation and function of human peripheral T cell and prevents T-cell-mediated immune response in mice. Clin Immunol. 2011;135(1):55–62.CrossRefGoogle Scholar
  57. 57.
    Krusch M, et al. The kinase inhibitors sunitinib and sorafenib differentially affect NK cell antitumor reactivity in vitro. J Immunol. 2009;183(12):8286–94.CrossRefPubMedGoogle Scholar
  58. 58.
    Zhao W, et al. Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK phosphorylation. Leukemia. 2008;22(6):1226–33.CrossRefPubMedGoogle Scholar
  59. 59.
    Molhoek KR, et al. Apoptosis of CD4(+)CD25(high) T cells in response to Sirolimus requires activation of T cell receptor and is modulated by IL-2. Cancer Immunol Immunother. 2009;58(6):867–76.CrossRefPubMedGoogle Scholar
  60. 60.
    Herman DC, Zhang YM, Miller RM. Rhamnolipid (biosurfactant) effects on cell aggregation and biodegradation of residual hexadecane under saturated flow conditions. Appl Environ Microbiol. 1997;63(9):3622–7.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Huo YY, et al. Marinobacterium nitratireducens sp. nov and Marinobacterium sediminicola sp. nov., isolated from marine sediment. Int J Syst Evol Microbiol. 2009;59:1173–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Fenwick RB, et al. Resonance assignments for the RLIP76 Ral binding domain in its free form and in complex with the small G protein RalB. Biomol NMR Assign. 2008;2(2):191–4.CrossRefPubMedGoogle Scholar
  63. 63.
    Koren-Morag N, Goldbourt U, Tanne D. Poor functional status based on the New York Heart Association classification exposes the coronary patient to an elevated risk of ischemic stroke. Am Heart J. 2008;155(3):515–20.CrossRefPubMedGoogle Scholar
  64. 64.
    Zerza G, Sassara A, Chergui M. Matrix isolation spectroscopy of C-70 – vibrational analysis and assignment of the lowest excited states. Synth Met. 1999;103(1–3):2386–7.CrossRefGoogle Scholar
  65. 65.
    Gollob JA, et al. Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol. 2007;25(22):3288–95.CrossRefPubMedGoogle Scholar
  66. 66.
    Ryan CW, et al. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol. 2007;25(22):3296–301.CrossRefPubMedGoogle Scholar
  67. 67.
    Mickisch GH, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001;358(9286):966–70.CrossRefPubMedGoogle Scholar
  68. 68.
    Flanigan RC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345(23):1655–9.CrossRefPubMedGoogle Scholar
  69. 69.
    McDermott D, et al. A randomized phase III trial of high-dose interleukin-2 (HD IL2) versus subcutaneous (SC) 112/interferon (IFN) in patients with metastatic renal cell carcinoma (RCC). Proc Am Soc Clin Oncol. 2001;20: abstr 685.Google Scholar
  70. 70.
    Pantuck AJ, Belldegrun AS, Figlin RA. Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. N Engl J Med. 2001;345(23):1711–2.CrossRefPubMedGoogle Scholar
  71. 71.
    Bennett RT, et al. Cytoreductive surgery for stage IV renal cell carcinoma. J Urol. 1995;154(1):32–4.CrossRefPubMedGoogle Scholar
  72. 72.
    Rackley R, et al. The impact of adjuvant nephrectomy on multimodality treatment of metastatic renal cell carcinoma. J Urol. 1994;152(5 Pt 1):1399–403.CrossRefPubMedGoogle Scholar
  73. 73.
    Taneja SS, et al. Immunotherapy for renal cell carcinoma: the era of interleukin-2-based treatment. Urology. 1995;45(6):911–24.CrossRefPubMedGoogle Scholar
  74. 74.
    Walther MM, et al. Cytoreductive surgery before high dose interleukin-2 based therapy in patients with metastatic renal cell carcinoma. J Urol. 1997;158(5):1675–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Fallick ML, et al. Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma. J Urol. 1997;158(5):1691–5.CrossRefPubMedGoogle Scholar
  76. 76.
    Dekernion JB, Ramming KP, Smith RB. The natural history of metastatic renal cell carcinoma: a computer analysis. J Urol. 1978;120(2):148–52.CrossRefPubMedGoogle Scholar
  77. 77.
    Belldegrun A, et al. Renal cell carcinoma: basic biology and current approaches to therapy. Semin Oncol. 1991;18(5 Suppl 7):96–101.PubMedGoogle Scholar
  78. 78.
    O’Dea MJ, et al. The treatment of renal cell carcinoma with solitary metastasis. J Urol. 1978;120(5):540–2.CrossRefPubMedGoogle Scholar
  79. 79.
    Tolia BM, Whitmore Jr WF. Solitary metastasis from renal cell carcinoma. J Urol. 1975;114(6):836–8.CrossRefPubMedGoogle Scholar
  80. 80.
    Kavolius JP, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998;16(6):2261–6.CrossRefPubMedGoogle Scholar
  81. 81.
    Dineen MK, et al. Results of surgical treatment of renal cell carcinoma with solitary metastasis. J Urol. 1988;140(2):277–9.CrossRefPubMedGoogle Scholar
  82. 82.
    Swanson DA. Surgery for metastases of renal cell carcinoma. Scand J Surg. 2004;93(2):150–5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Hematology-OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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