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Vol. 86, No. 1, 2011
Issue release date: February 2011
Urol Int 2011;86:53–59

The Effect of Sunitinib on Immune Subsets in Metastatic Clear Cell Renal Cancer

Powles T. · Chowdhury S. · Bower M. · Saunders N. · Lim L. · Shamash J. · Sarwar N. · Sadev A. · Peters J. · Green J. · Boleti K. · Augwal S.
aSt Bartholomew Hospital, bGuys’ and St. Thomas Hospital, cRoyal Free Hospital and dWhipps Cross University Hospital, London, UK

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Background: Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is associated with leucopenia; however, its effects on specific immune cell subsets are unclear. Alterations in immune cell subsets may contribute to tumour progression. Methods: Lymphocyte subsets (CD3, 4, 8, 19 and 56) were measured in 43 untreated MCRC patients who received sunitinib. The protocol included a structured treatment interruption of 5 weeks. Cell populations were measured at specific time points during sunitinib treatment and the treatment break. Results: Sunitinib was associated with significant declines in total leucocyte (–48%), neutrophil (–62%), CD3 total T cell (–31%) and CD4 counts (32%; p < 0.05). There was no significant change in CD19 B lymphocyte, CD8 or CD56 natural killer cells. During the sunitinib-free interval, all parameters recovered to baseline. No patients developed opportunistic infections or neutropenic sepsis. The level of specific immune subsets at presentation or occurrence of a fall in specific counts had an effect on progression-free survival (p > 0.05). Conclusions: Sunitinib is associated with reversible inhibition of specific lymphocyte subsets which has implications for the immunological control of MCRC and its use in combination with other agents. Despite suppressive effects, there was no evidence of predisposition to immune suppressive-related infection.

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  1. McDermott DF: Immunotherapy of metastatic renal cell carcinoma. Cancer 2009;115(suppl 10):2298–2305.

    External Resources

  2. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115–124.
  3. Chung EK, Stadler WM: Vascular endothelial growth factor pathway-targeted therapy as initial systemic treatment of patients with renal cancer. Clin Genitourin Cancer 2008;6(suppl 1):S22–S28.
  4. Atkins MB: Treatment selection for patients with metastatic renal cell carcinoma: identification of features favoring upfront IL-2-based immunotherapy. Med Oncol 2009;26(suppl 1):18–22.
  5. Motzer RJ, Hudes G, Wilding G, Schwartz LH, Hariharan S, Kempin S, Fayyad R, Figlin RA: Phase I trial of sunitinib malate plus interferon-alpha for patients with metastatic renal cell carcinoma. Clin Genitourin Cancer 2009;7:28–33.
  6. Kroog GS, Feldman DR, Kondagunta GV, Ginsberg PM, Fischer MJ, Trinos S, Patil NM, Ishill NM, Motzer RJ: Phase I trial of RAD001 (everolimus) plus sunitinib in patients with metastatic renal cell carcinoma (abstract 5037). J Clin Oncol 2009;27(suppl):15s.
  7. Reck MN, Frickhofen U, Gatzemeier H, Fuhr S, Lanzalone MJ, Lechuga E, Wang R, Chao E, Felip R: A phase I dose escalation study of sunitinib in combination with gemcitabine + cisplatin for advanced non-small cell lung cancer (NSCLC). 2007 ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007;25(suppl):18057.
  8. Zhu AX, Duda DG, Sahani DV, Jain RK: Development of sunitinib in hepatocellular carcinoma: rationale, early clinical experience, and correlative studies. Cancer J 2009;15:263–268.
  9. Kao J, Packer S, Vu HL, Schwartz ME, Sung MW, Stock RG, Lo YC, Huang D, Chen SH, Cesaretti JA: Phase 1 study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response. Cancer 2009;115:3571–3580.
  10. Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, Mazumdar M: Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 2004;22:454–463.
  11. Powles T, Imami N, Nelson M, Gazzard BG, Bower M: Effects of combination chemotherapy and highly active antiretroviral therapy on immune parameters in HIV-1 associated lymphoma. AIDS 2002;16:531–536.
  12. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 2009;15:2148–2157.
  13. Finke JH, Rini B, Ireland J, Rayman P, Richmond A, Golshayan A, Wood L, Elson P, Garcia J, Dreicer R, Bukowski R: Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 2008;14:6674–6682.
  14. Rini BI, Michaelson MD, Rosenberg JE, Bukowski RM, Sosman JA, Stadler WM, Hutson TE, Margolin K, Harmon CS, DePrimo SE, Kim ST, Chen I, George DJ: Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J Clin Oncol 2008;26:3743–3748.
  15. Norden-Zfoni A, Desai J, Manola J, Beaudry P, Force J, Maki R, Folkman J, Bello C, Baum C, DePrimo SE, Shalinsky DR, Demetri GD, Heymach JV: Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res 20071;13:2643–2650.

    External Resources

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