Renal cell carcinoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farima Kahe M.D. [2]

Overview

The medical therapies of renal cell carcinoma include chemotherapy, hormone treatment, immunotherapy, and targeted therapy.

Medical Therapy

Medical therapy is generally reserved for patients with metastatic disease when surgical management is not feasible. The goal of medical therapy is to achieve an appropriate overall quality of life and to control tumor burden. Most patients who require systemic medical therapy continue treatment chronically.

In summary, the following table shows the response rate of various treatment options for renal cell carcinoma:

Summary of Medical Therapy for Metastatic Renal Cell Carcinoma[1]
Objective Response Rate
Hormone Treatment[2] 2%
Chemotherapy[3][4] 5-6&
Aldesleukin (IL2)[5][6] 21-23% at high dose
10% at low dose
Interferon alfa[2][7][8] 10-15%
Sunitinib[9][10][11] 30-45%
Sorafenib[12][13] 30-45%
Bevacizumab[14][15][16] 30-45%
Temsirolimus[17][18] 30-45%
Adapted from Rini BI, Campbell SC, and Escudier B. Renal cell carcinoma.Lancet.2009; 373(9669):1119-32.

Immunotherapy

Immunotherapy is considered the first line therapy for patients with metastatic renal cell carcinoma.[19][20][21][5][6][22]

Targeted therapy

VEGF Neutralizing Antibody

Sunitinib Malate
Sorafenib Tosylate
  • Sorafenib tosylate is a kinase inhibitor of VEGF receptor, often regarded as a weaker inhibitor than sunitinib.
  • Sorafenib has shown approximately a significant additional 3 month progression free survival and similarly, a significant additional median overall survival of approximately 3.4 months.[12]
  • Associated toxicity includes those of sunitinib but at a lesser rate.

Bevacizumab

  • Monoclonal antibody against VEGF considered first line therapy in Europe.[27][1]
  • Response rate and progression free survival are both increased with combination with inferferon.[14]
  • Toxicity includes fatigue, anorexia, hypertension, and proteinuria.[1]
EGFR-Neutralizing Antibody

Epidermal growth factor receptor (EGFR) inhibitors are used less frequently than VEGF inhibitors. Examples of EGFR inhibitors are listed below[28]:

mTOR Inhibitors

Temsirolimus

Chemotherapy

  • Vinblastine
    • Vinblastine has shown to be ineffective in metastatic renal cell carcinoma.[33]
    • Combination with other agents has not shown added benefit either.[34]

Hormone Therapy

Medroxyprogesterone

  • Large randomized trials did not yield high responses as anti-tumor effects when used alone or when used with other medications.[33][34]
  • Their role is reserved for palliative care.[2][3][4]

References

  1. ↑ 1.0 1.1 1.2 Rini BI, Campbell SC, Escudier B (2009). "Renal cell carcinoma". Lancet. 373 (9669): 1119–32. doi:10.1016/S0140-6736(09)60229-4. PMID 19269025.
  2. ↑ 2.0 2.1 2.2 "Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators". Lancet. 353 (9146): 14–7. 1999. PMID 10023944.
  3. ↑ 3.0 3.1 Yagoda A, Abi-Rached B, Petrylak D (1995). "Chemotherapy for advanced renal-cell carcinoma: 1983-1993". Semin Oncol. 22 (1): 42–60. PMID 7855619.
  4. ↑ 4.0 4.1 Motzer RJ, Russo P (2000). "Systemic therapy for renal cell carcinoma". J Urol. 163 (2): 408–17. PMID 10647643.
  5. ↑ 5.0 5.1 McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF; et al. (2005). "Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma". J Clin Oncol. 23 (1): 133–41. doi:10.1200/JCO.2005.03.206. PMID 15625368.
  6. ↑ 6.0 6.1 Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P; et al. (2003). "Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer". J Clin Oncol. 21 (16): 3127–32. doi:10.1200/JCO.2003.02.122. PMC 2275327. PMID 12915604.
  7. ↑ Pyrhönen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T; et al. (1999). "Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer". J Clin Oncol. 17 (9): 2859–67. PMID 10561363.
  8. ↑ Miller AB, Hoogstraten B, Staquet M, Winkler A (1981). "Reporting results of cancer treatment". Cancer. 47 (1): 207–14. PMID 7459811.
  9. ↑ 9.0 9.1 Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA; et al. (2006). "Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma". J Clin Oncol. 24 (1): 16–24. doi:10.1200/JCO.2005.02.2574. PMID 16330672.
  10. ↑ 10.0 10.1 Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR; et al. (2006). "Sunitinib in patients with metastatic renal cell carcinoma". JAMA. 295 (21): 2516–24. doi:10.1001/jama.295.21.2516. PMID 16757724.
  11. ↑ 11.0 11.1 Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O; et al. (2007). "Sunitinib versus interferon alfa in metastatic renal-cell carcinoma". N Engl J Med. 356 (2): 115–24. doi:10.1056/NEJMoa065044. PMID 17215529.
  12. ↑ 12.0 12.1 Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M; et al. (2007). "Sorafenib in advanced clear-cell renal-cell carcinoma". N Engl J Med. 356 (2): 125–34. doi:10.1056/NEJMoa060655. PMID 17215530.
  13. ↑ Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F; et al. (2009). "Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma". J Clin Oncol. 27 (8): 1280–9. doi:10.1200/JCO.2008.19.3342. PMID 19171708.
  14. ↑ 14.0 14.1 Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C; et al. (2007). "Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial". Lancet. 370 (9605): 2103–11. doi:10.1016/S0140-6736(07)61904-7. PMID 18156031.
  15. ↑ Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS; et al. (2008). "Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206". J Clin Oncol. 26 (33): 5422–8. doi:10.1200/JCO.2008.16.9847. PMC 2651074. PMID 18936475.
  16. ↑ Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL; et al. (2003). "A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer". N Engl J Med. 349 (5): 427–34. doi:10.1056/NEJMoa021491. PMC 2275324. PMID 12890841.
  17. ↑ Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR; et al. (2004). "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. 22 (5): 909–18. doi:10.1200/JCO.2004.08.185. PMID 14990647.
  18. ↑ Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A; et al. (2007). "Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma". N Engl J Med. 356 (22): 2271–81. doi:10.1056/NEJMoa066838. PMID 17538086.
  19. ↑ Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A; et al. (2005). "Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer". Clin Cancer Res. 11 (10): 3714–21. doi:10.1158/1078-0432.CCR-04-2019. PMID 15897568.
  20. ↑ Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y; et al. (2003). "Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy". Clin Cancer Res. 9 (2): 802–11. PMID 12576453.
  21. ↑ Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB (2005). "Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy". J Immunother. 28 (5): 488–95. PMID 16113605.
  22. ↑ Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C; et al. (1998). "Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie". N Engl J Med. 338 (18): 1272–8. doi:10.1056/NEJM199804303381805. PMID 9562581.
  23. ↑ Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G; et al. (2003). "In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship". Clin Cancer Res. 9 (1): 327–37. PMID 12538485.
  24. ↑ Rini BI, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L; et al. (2007). "Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib". J Natl Cancer Inst. 99 (1): 81–3. doi:10.1093/jnci/djk008. PMID 17202116.
  25. ↑ Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L; et al. (2007). "Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib". Lancet. 370 (9604): 2011–9. doi:10.1016/S0140-6736(07)61865-0. PMC 2643085. PMID 18083403.
  26. ↑ Khakoo AY, Kassiotis CM, Tannir N, Plana JC, Halushka M, Bickford C; et al. (2008). "Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor". Cancer. 112 (11): 2500–8. doi:10.1002/cncr.23460. PMID 18386829.
  27. ↑ Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L; et al. (1997). "Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders". Cancer Res. 57 (20): 4593–9. PMID 9377574.
  28. ↑ Cohen HT, McGovern FJ (2005). "Renal-cell carcinoma". N Engl J Med. 353 (23): 2477–90. doi:10.1056/NEJMra043172. PMID 16339096.
  29. ↑ Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999). "Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma". J Clin Oncol. 17 (8): 2530–40. PMID 10561319.
  30. ↑ Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P; et al. (2005). "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. 23 (4): 832–41. doi:10.1200/JCO.2005.05.179. PMID 15681528.
  31. ↑ Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S; et al. (2008). "Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial". Lancet. 372 (9637): 449–56. doi:10.1016/S0140-6736(08)61039-9. PMID 18653228.
  32. ↑ Rini BI, Vogelzang NJ, Dumas MC, Wade JL, Taber DA, Stadler WM (2000). "Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer". J Clin Oncol. 18 (12): 2419–26. PMID 10856102.
  33. ↑ 33.0 33.1 Fosså SD, Droz JP, Pavone-Macaluso MM, Debruyne FJ, Vermeylen K, Sylvester R (1992). "Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group". Eur J Cancer. 28A (4–5): 878–80. PMID 1524914.
  34. ↑ 34.0 34.1 Neidhart JA, Anderson SA, Harris JE, Rinehart JJ, Laszlo J, Dexeus FH; et al. (1991). "Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases". J Clin Oncol. 9 (5): 832–6. PMID 2016626.
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