Management of Metastatic Renal Cancer

The purpose of this article is to review the systemic management options for patients with metastatic renal cancer. We reviewed the literature regarding systemic management of metastatic renal cancer. Treatment options of chemotherapy agents, immunotherapy, molecularly targeted agents, allogeneic stem cell transplantation, vaccines, and other manipulations of the immune system are discussed. No chemotherapy agent used alone or in combination has consistently produced responses to substantiate its routine use. Interleukin-2 (IL-2) and interferon-α (IFN-α) have shown response rates ranging from 10% to 20%. Some studies have shown that retinoids may enhance the antitumor activity of IFN-α. Molecularly targeted agents and angiogenic agents are being actively pursued and several studies are showing response rates above 30%. Although nonmyeloablative allogeneic stem cell transplantation shows some promising results, they also have limitations to its use. Therapy strategies that incorporate vaccines as part of comprehensive immune manipulations are also being studied. The systemic treatment of patients with advanced renal cell cancer continues to be a significant challenge. Immunotherapy treatment has shown response in up to 20% of patients. Unfortunately, most do not respond. The current technologies are promising and may be the key step for introduction of better treatments for renal cancer care.

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Correspondence: Mayer Fishman, MD, PhD, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer and Research Institute, MCC-4035, 12902 Magnolia Drive, Tampa, FL 33612.E-mail: FishmaMN@moffitt.usf.edu
  • 1

    JemalATiwariRC. Cancer statistics, 2004. CA Cancer J Clin2004;54:829.

  • 2

    FishmanMSeigneJ. Immunotherapy of metastatic renal cell cancer. Review. Cancer Control2002;9:293304.

  • 3

    MotzerRJBanderNHNanusDM. Renal-cell carcinoma. N Engl J Med1996;335:865875.

  • 4

    MotzerRJMazumdarMBacikJ. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol1999;17:25302540.

    • Search Google Scholar
    • Export Citation
  • 5

    ZismanAmnonPantuckAllan J.DoreyFredrick. Mathematical model to predict individual survival for patients with renal cell carcinoma. J Clin Oncol2002;20:13681374.

    • Search Google Scholar
    • Export Citation
  • 6

    FlaniganRCMickischGSylvesterR. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol2004;171:10711076.

    • Search Google Scholar
    • Export Citation
  • 7

    MotzerRJRussoP. Systemic therapy for renal cell carcinoma. J Urol2000;163:408417.

  • 8

    RiniBLVogelzangNJDumasMC. Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol2000;18:24192426.

    • Search Google Scholar
    • Export Citation
  • 9

    RyanCWVogelzangNJStadlerW. A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and intereferon-alpha in patients with metastatic renal cell carcinoma. Cancer2002;94:26022609.

    • Search Google Scholar
    • Export Citation
  • 10

    HrusheskyWJvon RoemelingRLanningRM. Cicardian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. J Clin Oncol1990;8:15041513.

    • Search Google Scholar
    • Export Citation
  • 11

    ConroyTGeoffroisLGuilleminF. Simplified chronomodulated continuous infusion of floxuridine in patients with metastatic renal cell carcinoma. Cancer1993;72:21902197.

    • Search Google Scholar
    • Export Citation
  • 12

    BjarnasonGAHrusheskyWJDiasioR. Flat versus cicardian modified 14 day infusion of FUDR for advanced renal cell cancer (RCC): A phase III study(abstract). Proc Am Soc Clin Oncol1994;13:233.

    • Search Google Scholar
    • Export Citation
  • 13

    WenzelCLockerGJBartschR. Capecitabine monotherapy and in combination with immunotherapy in the treatment of metastatic renal cell carcinoma. Anticancer Drugs2003;14:779784.

    • Search Google Scholar
    • Export Citation
  • 14

    ChangDZOlenckiTBuddGT el al. Phase I trial of capecitabine in combination with interferon alpha in patients with metastatic renal cancer: toxicity and pharmacokinetics. Cancer Chemother Pharmacol2001;48:493498.

    • Search Google Scholar
    • Export Citation
  • 15

    WenzelCLockerGJSchmidingerM. Capecitabine in the treatment of metastatic renal cell carcinoma failing immunotherapy. Am J Kidney Dis2002;39:4854.

    • Search Google Scholar
    • Export Citation
  • 16

    WaterJSMossCHackettM. A phase II trial of gemcitabine (GEM) plus capecitabine (CAPE) in patients with metastatic renal cell carcinoma (MRCC)(Abstr #1549). Proc Am Soc Clin Oncol2003;22:386.

    • Search Google Scholar
    • Export Citation
  • 17

    StadlerWMHalabiSErnstoffR. 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(Abstr #4515). Proc Am Soc Clin Oncol23:2004.

    • Search Google Scholar
    • Export Citation
  • 18

    PortaCZimatoreMImarisioI. Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy-resistant advanced renal cell carcinoma: final results of a single-institution Phase II study. Cancer2004;100:21322138.

    • Search Google Scholar
    • Export Citation
  • 19

    LeeYVassilakosAFengN. GTI-2040, an antisense agent targeting the small subunit component (R2) of human ribonucleotide reductase, shows potent antitumor activity against a variety of tumors. Cancer Res2003;63:28022811.

    • Search Google Scholar
    • Export Citation
  • 20

    TownsleyCAChiKErnstDS. 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 Oncol2003;21:15241529.

    • Search Google Scholar
    • Export Citation
  • 21

    OjimaIChakravartySInoueT. A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc Natl Acad Sci U S A1999;96:42564261.

    • Search Google Scholar
    • Export Citation
  • 22

    ZhuangSHMenefeeHKotzM. A phase II clinical trial of BMS-247550 (ixabepilone), a mictobule-stabilizing agent in renal cell cancer(Abstr #4550). Proc Am Soc Clin Oncol2004;22:394A.

    • Search Google Scholar
    • Export Citation
  • 23

    PeyromaureMThiounnNScotteF. Collecting duct carcinoma of the kidney: A clinicopathological study of 9 cases. J Urol2003;170:11381140.

    • Search Google Scholar
    • Export Citation
  • 24

    EscudierBDrozJPRollandF. for the Genitourinary Group of the French Federation of Cancer Centers. Doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma: a phase II study of the Genitourinary Group of the French Federation of Cancer Centers. J Urol2002;168:959961.

    • Search Google Scholar
    • Export Citation
  • 25

    RosenbergSALotzeMRMuulLM. 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 Med1987;316: 889897.

    • Search Google Scholar
    • Export Citation
  • 26

    BergWJBukowskiRThompsonJA. A randomized phase II trial of recombinant human interleukin-12 (IL-12) versus interferon alpha-2a (IFN) in advanced renal cell carcinoma. Proc Am Soc Clin Oncol1998; 17:318(abstract #1226).

    • Search Google Scholar
    • Export Citation
  • 27

    FisherRIRosenbergSAFyfeG. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am2000;6(suppl 1):S55S57.

    • Search Google Scholar
    • Export Citation
  • 28

    YangJCSherryRMSteinbergSM. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol2003;21:31273132.

    • Search Google Scholar
    • Export Citation
  • 29

    WirthMP. Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am1993;20:283295.

  • 30

    MinasianLMMotzerRJGluckL. Interferon alfa-2a in advanced renal cell carcinoma: Treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol1993;11:13681375.

    • Search Google Scholar
    • Export Citation
  • 31

    NeidhartJAAndersonSAHarrisJE. Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases. J Clin Oncol1991;9:832836.

    • Search Google Scholar
    • Export Citation
  • 32

    PyrohenSSalminenERuutuM. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol1999;17:28592867.

    • Search Google Scholar
    • Export Citation
  • 33

    BerlinJKingACTutschK. A phase II study of vinblastine in combination with acrivastin in patients with advanced renal cell carcinoma. Invest New Drugs1994;12:137141.

    • Search Google Scholar
    • Export Citation
  • 34

    MurphyBRRynardSMPenningtonKL. A phase II trial of vinblastine and dipyridamole in advanced renal cell carcinoma: A Hoosier Oncology Group Study. Am J Clin Oncol1994;17:1013.

    • Search Google Scholar
    • Export Citation
  • 35

    BukowskiRErnstoffMSGoreME. Pegylated interferon alfa-2b treatment for patients with solid tumors: A phase I/II study. J Clin Oncol2002;20:38413849.

    • Search Google Scholar
    • Export Citation
  • 36

    MotzerRJRakhitAGinsbergM. Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. J Clin Oncol2001;19:13121319.

    • Search Google Scholar
    • Export Citation
  • 37

    EliasLBlumensteinBAKishJ. A phase II trial of interferon-alpha and 5-fluorouracil in patients with advanced renal cell carcinoma: A Southwest Oncology Group study. Cancer1996;78:10851088.

    • Search Google Scholar
    • Export Citation
  • 38

    AtkinsMBDutcherJWeissG. Kidney Cancer: the Cytokine Working Group experience (1986-2001): Part I. IL-2 based clinical trials. Review. Med Oncol2001;18:197207.

    • Search Google Scholar
    • Export Citation
  • 39

    AtzpodienJKirchnerHJonasU. Interleukin-2 and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: A prospectively randomized trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol2004;22:11881194. Epub.

    • Search Google Scholar
    • Export Citation
  • 40

    Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: A cytokine working group randomized trial. J Clin Oncol2003;21:31333140.

    • Search Google Scholar
    • Export Citation
  • 41

    FiglinRGitlitzBFranklinJ. Interleukin-2 based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients. Cancer J Sci Am1997;3(suppl 1):S92S97.

    • Search Google Scholar
    • Export Citation
  • 42

    FossaSDMickischGHDe MulderPH. Interferon-alpha-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma. Cancer2004;101:533540.

    • Search Google Scholar
    • Export Citation
  • 43

    MotzerRJMurphyBABacikJ. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol2000;18:29722980.

    • Search Google Scholar
    • Export Citation
  • 44

    SiemannDWChaplinDJHorsmanMR. Vascular-targeting therapies for treatment of malignant disease. Cancer2004;100:24912499.

  • 45

    DruckerBJSchwartzLMarionS. Phase II trial of ZD1839 (Iressa), an EGF receptor inhibitor, in patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol2002;21:720A.

    • Search Google Scholar
    • Export Citation
  • 46

    DawsonNAGuoCZakR. A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma(Abstr #4500). Proc Am Soc Clin Oncol2003;22:404.

    • Search Google Scholar
    • Export Citation
  • 47

    YangJCHaworthLSherryRM. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med2003;349:427434.

    • Search Google Scholar
    • Export Citation
  • 48

    RiniBIHalabiSTaylorJ. Cancer and Leukemia Group B90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin Cancer Res2004;10:25842586.

    • Search Google Scholar
    • Export Citation
  • 49

    MotzerRJRiniBIMichaelsonBG. SU011248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: Results of a phase 2 trial(Abstr #4500). Proc Am Soc Clin Oncol2004;22:145.

    • Search Google Scholar
    • Export Citation
  • 50

    AtkinsMBHidalgoMStadlerWM. 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 Oncol2004;22:909918.

    • Search Google Scholar
    • Export Citation
  • 51

    HidalgoMAtkinsMBStadlerWM. A randomized double-blind phase II study o f intravenous CCI-779 administered weekly to patients with advanced renal cell carcinoma-prognostic factor analysis(Abstr). Proc Am Soc Clin Oncol2003;22:201a.

    • Search Google Scholar
    • Export Citation
  • 52

    RatainMJFlahertyKTStadlerWM. 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). ASCO Meeting Abstracts2004:382.

    • Search Google Scholar
    • Export Citation
  • 53

    EscudierBLassauNCouanetD. Phase II trial of thalidomide in renal-cell carcinoma. Ann Oncol2002;13:10291035.

  • 54

    AmatoRJSchellJThompsonN. Phase II study of thalidomide + interleukin-2 in patients with metastatic renal cell carcinoma(Abstr). Proc Am Soc Clin Oncol2003;22:387a.

    • Search Google Scholar
    • Export Citation
  • 55

    OlenckiTDreicerRElsonP. Phase I trial of thalidomide and interleukin-2 (IL-2) in patients (pts) with metastatic renal cell carcinoma (RCC)(Abstr #2430). Proc Am Soc Clin Onc2002.

    • Search Google Scholar
    • Export Citation
  • 56

    GordonMSManolaJFaircloughD. Low dose interferon-α2b (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). J Clin Oncol2004;22(Suppl):4516.

    • Search Google Scholar
    • Export Citation
  • 57

    ThorpePE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res2004;10:415427.

  • 58

    BregniMDoderoAPeccatoriJ. Nonmyeoloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood2002;99:42344236.

    • Search Google Scholar
    • Export Citation
  • 59

    ChildsRChernoffAContentinN. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med2000;343:750758.

    • Search Google Scholar
    • Export Citation
  • 60

    UenoNTChengYCRondonG. 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;102:38293836. Epub.

    • Search Google Scholar
    • Export Citation
  • 61

    BlaiseDBayJOFaucherC. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood2004;103:435441.

    • Search Google Scholar
    • Export Citation
  • 62

    NakagawaTKamiMHoriA. Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: Single institution experience with a minimum 1-year follow-up. Exp Hematol2004;32: 599606.

    • Search Google Scholar
    • Export Citation
  • 63

    JochamDRichterAHoffmannL. 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;363:594599.

    • Search Google Scholar
    • Export Citation
  • 64

    FishmanMAntoniaS. Specific antitumour vaccine for renal cancerLancet.2004;363:583584594599.

  • 65

    RosenbergSAYangJCRestifoNP. Cancer immunotherapy: moving beyond current vaccines. Nat Med2004;10:909915.

  • 66

    WirthMP: Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am1993;20:283295.

  • 67

    RosenbergSAYangJCTopalianSL. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA1994;271:907913.

    • Search Google Scholar
    • Export Citation
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