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

    Jemal A, Tiwari RC. Cancer statistics, 2004. CA Cancer J Clin 2004;54:829.

  • 2

    Fishman M, Seigne J. Immunotherapy of metastatic renal cell cancer. Review. Cancer Control 2002;9:293304.

  • 3

    Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996;335:865875.

  • 4

    Motzer RJ, Mazumdar M, Bacik J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:25302540.

    • Search Google Scholar
    • Export Citation
  • 5

    Zisman Amnon, Pantuck Allan J., Dorey Fredrick. Mathematical model to predict individual survival for patients with renal cell carcinoma. J Clin Oncol 2002;20:13681374.

    • Search Google Scholar
    • Export Citation
  • 6

    Flanigan RC, Mickisch G, Sylvester R. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004;171:10711076.

    • Search Google Scholar
    • Export Citation
  • 7

    Motzer RJ, Russo P. Systemic therapy for renal cell carcinoma. J Urol 2000;163:408417.

  • 8

    Rini BL, Vogelzang NJ, Dumas MC. Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol 2000;18:24192426.

    • Search Google Scholar
    • Export Citation
  • 9

    Ryan CW, Vogelzang NJ, Stadler W. A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and intereferon-alpha in patients with metastatic renal cell carcinoma. Cancer 2002;94:26022609.

    • Search Google Scholar
    • Export Citation
  • 10

    Hrushesky WJ, von Roemeling R, Lanning RM. Cicardian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. J Clin Oncol 1990;8:15041513.

    • Search Google Scholar
    • Export Citation
  • 11

    Conroy T, Geoffrois L, Guillemin F. Simplified chronomodulated continuous infusion of floxuridine in patients with metastatic renal cell carcinoma. Cancer 1993;72:21902197.

    • Search Google Scholar
    • Export Citation
  • 12

    Bjarnason GA, Hrushesky WJ, Diasio R. Flat versus cicardian modified 14 day infusion of FUDR for advanced renal cell cancer (RCC): A phase III study (abstract). Proc Am Soc Clin Oncol 1994;13:233.

    • Search Google Scholar
    • Export Citation
  • 13

    Wenzel C, Locker GJ, Bartsch R. Capecitabine monotherapy and in combination with immunotherapy in the treatment of metastatic renal cell carcinoma. Anticancer Drugs 2003;14:779784.

    • Search Google Scholar
    • Export Citation
  • 14

    Chang DZ, Olencki T, Budd GT, el al. Phase I trial of capecitabine in combination with interferon alpha in patients with metastatic renal cancer: toxicity and pharmacokinetics. Cancer Chemother Pharmacol 2001;48:493498.

    • Search Google Scholar
    • Export Citation
  • 15

    Wenzel C, Locker GJ, Schmidinger M. Capecitabine in the treatment of metastatic renal cell carcinoma failing immunotherapy. Am J Kidney Dis 2002;39:4854.

    • Search Google Scholar
    • Export Citation
  • 16

    Water JS, Moss C, Hackett M. A phase II trial of gemcitabine (GEM) plus capecitabine (CAPE) in patients with metastatic renal cell carcinoma (MRCC) (Abstr #1549). Proc Am Soc Clin Oncol 2003;22:386.

    • Search Google Scholar
    • Export Citation
  • 17

    Stadler WM, Halabi S, Ernstoff R. 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 Oncol 23:2004.

    • Search Google Scholar
    • Export Citation
  • 18

    Porta C, Zimatore M, Imarisio I. Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy-resistant advanced renal cell carcinoma: final results of a single-institution Phase II study. Cancer 2004;100:21322138.

    • Search Google Scholar
    • Export Citation
  • 19

    Lee Y, Vassilakos A, Feng N. 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 Res 2003;63:28022811.

    • Search Google Scholar
    • Export Citation
  • 20

    Townsley CA, Chi K, Ernst DS. 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;21:15241529.

    • Search Google Scholar
    • Export Citation
  • 21

    Ojima I, Chakravarty S, Inoue T. A common pharmacophore for cytotoxic natural products that stabilize microtubules. Proc Natl Acad Sci U S A 1999;96:42564261.

    • Search Google Scholar
    • Export Citation
  • 22

    Zhuang SH, Menefee H, Kotz M. A phase II clinical trial of BMS-247550 (ixabepilone), a mictobule-stabilizing agent in renal cell cancer (Abstr #4550). Proc Am Soc Clin Oncol 2004;22:394A.

    • Search Google Scholar
    • Export Citation
  • 23

    Peyromaure M, Thiounn N, Scotte F. Collecting duct carcinoma of the kidney: A clinicopathological study of 9 cases. J Urol 2003;170:11381140.

    • Search Google Scholar
    • Export Citation
  • 24

    Escudier B, Droz JP, Rolland F., 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 Urol 2002;168:959961.

    • Search Google Scholar
    • Export Citation
  • 25

    Rosenberg SA, Lotze MR, Muul LM. 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: 889897.

    • Search Google Scholar
    • Export Citation
  • 26

    Berg WJ, Bukowski R, Thompson JA. 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 Oncol 1998; 17:318 (abstract #1226).

    • Search Google Scholar
    • Export Citation
  • 27

    Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 2000;6(suppl 1):S55S57.

    • Search Google Scholar
    • Export Citation
  • 28

    Yang JC, Sherry RM, Steinberg SM. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003;21:31273132.

    • Search Google Scholar
    • Export Citation
  • 29

    Wirth MP. Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am 1993;20:283295.

  • 30

    Minasian LM, Motzer RJ, Gluck L. Interferon alfa-2a in advanced renal cell carcinoma: Treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 1993;11:13681375.

    • Search Google Scholar
    • Export Citation
  • 31

    Neidhart JA, Anderson SA, Harris JE. Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases. J Clin Oncol 1991;9:832836.

    • Search Google Scholar
    • Export Citation
  • 32

    Pyrohen S, Salminen E, Ruutu M. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 1999;17:28592867.

    • Search Google Scholar
    • Export Citation
  • 33

    Berlin J, King AC, Tutsch K. A phase II study of vinblastine in combination with acrivastin in patients with advanced renal cell carcinoma. Invest New Drugs 1994;12:137141.

    • Search Google Scholar
    • Export Citation
  • 34

    Murphy BR, Rynard SM, Pennington KL. A phase II trial of vinblastine and dipyridamole in advanced renal cell carcinoma: A Hoosier Oncology Group Study. Am J Clin Oncol 1994;17:1013.

    • Search Google Scholar
    • Export Citation
  • 35

    Bukowski R, Ernstoff MS, Gore ME. Pegylated interferon alfa-2b treatment for patients with solid tumors: A phase I/II study. J Clin Oncol 2002;20:38413849.

    • Search Google Scholar
    • Export Citation
  • 36

    Motzer RJ, Rakhit A, Ginsberg M. Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. J Clin Oncol 2001;19:13121319.

    • Search Google Scholar
    • Export Citation
  • 37

    Elias L, Blumenstein BA, Kish J. A phase II trial of interferon-alpha and 5-fluorouracil in patients with advanced renal cell carcinoma: A Southwest Oncology Group study. Cancer 1996;78:10851088.

    • Search Google Scholar
    • Export Citation
  • 38

    Atkins MB, Dutcher J, Weiss G. Kidney Cancer: the Cytokine Working Group experience (1986-2001): Part I. IL-2 based clinical trials. Review. Med Oncol 2001;18:197207.

    • Search Google Scholar
    • Export Citation
  • 39

    Atzpodien J, Kirchner H, Jonas U. 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 Oncol 2004;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 Oncol 2003;21:31333140.

    • Search Google Scholar
    • Export Citation
  • 41

    Figlin R, Gitlitz B, Franklin J. Interleukin-2 based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients. Cancer J Sci Am 1997;3(suppl 1):S92S97.

    • Search Google Scholar
    • Export Citation
  • 42

    Fossa SD, Mickisch GH, De Mulder PH. Interferon-alpha-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma. Cancer 2004;101:533540.

    • Search Google Scholar
    • Export Citation
  • 43

    Motzer RJ, Murphy BA, Bacik J. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol 2000;18:29722980.

    • Search Google Scholar
    • Export Citation
  • 44

    Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer 2004;100:24912499.

  • 45

    Drucker BJ, Schwartz L, Marion S. Phase II trial of ZD1839 (Iressa), an EGF receptor inhibitor, in patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol 2002;21:720A.

    • Search Google Scholar
    • Export Citation
  • 46

    Dawson NA, Guo C, Zak R. A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma (Abstr #4500). Proc Am Soc Clin Oncol 2003;22:404.

    • Search Google Scholar
    • Export Citation
  • 47

    Yang JC, Haworth L, Sherry RM. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427434.

    • Search Google Scholar
    • Export Citation
  • 48

    Rini BI, Halabi S, Taylor J. 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 Res 2004;10:25842586.

    • Search Google Scholar
    • Export Citation
  • 49

    Motzer RJ, Rini BI, Michaelson BG. 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 Oncol 2004;22:145.

    • Search Google Scholar
    • Export Citation
  • 50

    Atkins MB, Hidalgo M, Stadler WM. 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;22:909918.

    • Search Google Scholar
    • Export Citation
  • 51

    Hidalgo M, Atkins MB, Stadler WM. 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 Oncol 2003;22:201a.

    • Search Google Scholar
    • Export Citation
  • 52

    Ratain MJ, Flaherty KT, Stadler WM. 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 Abstracts 2004:382.

    • Search Google Scholar
    • Export Citation
  • 53

    Escudier B, Lassau N, Couanet D. Phase II trial of thalidomide in renal-cell carcinoma. Ann Oncol 2002;13:10291035.

  • 54

    Amato RJ, Schell J, Thompson N. Phase II study of thalidomide + interleukin-2 in patients with metastatic renal cell carcinoma (Abstr). Proc Am Soc Clin Oncol 2003;22:387a.

    • Search Google Scholar
    • Export Citation
  • 55

    Olencki T, Dreicer R, Elson P. 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 Onc 2002.

    • Search Google Scholar
    • Export Citation
  • 56

    Gordon MS, Manola J, Fairclough D. 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 Oncol 2004;22(Suppl):4516.

    • Search Google Scholar
    • Export Citation
  • 57

    Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004;10:415427.

  • 58

    Bregni M, Dodero A, Peccatori J. Nonmyeoloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 2002;99:42344236.

    • Search Google Scholar
    • Export Citation
  • 59

    Childs R, Chernoff A, Contentin N. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 2000;343:750758.

    • Search Google Scholar
    • Export Citation
  • 60

    Ueno NT, Cheng YC, Rondon G. 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

    Blaise D, Bay JO, Faucher C. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 2004;103:435441.

    • Search Google Scholar
    • Export Citation
  • 62

    Nakagawa T, Kami M, Hori A. 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 Hematol 2004;32: 599606.

    • Search Google Scholar
    • Export Citation
  • 63

    Jocham D, Richter A, Hoffmann L. 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

    Fishman M, Antonia S. Specific antitumour vaccine for renal cancer Lancet. 2004;363:583584, 594599.

  • 65

    Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004;10:909915.

  • 66

    Wirth MP: Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am 1993;20:283295.

  • 67

    Rosenberg SA, Yang JC, Topalian SL. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994;271:907913.

    • Search Google Scholar
    • Export Citation
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