Targeted Therapy for Metastatic Renal Carcinoma: an Update
Main Article Content
Keywords
Kidney Cancer, RCC, targeted therapy
Abstract
Conventional chemotherapy is associated with poor outcomes in metastatic renal cell carcinoma (RCC). Advances in the understanding of tumor molecular biology and the implementation of new drugs that target these molecular pathways have increased the arsenal against advanced RCC and improved outcomes in these patients. Herein, we briefly describe the latest data on targeted therapies used in the treatment of advanced renal cell carcinoma. Search strategy was performed according to PRISMA guidelines. Abstracts of relevant studies published in PubMed between 2000 and 2014 were analyzed by two authors. Abstracts were selected if they were published in English, data reported was of phase II or III clinical trials, and outcomes followed FDA approval. If consensus between the two authors was achieved, they were included in the review. Key words used were “target therapy” and “metastatic renal cell carcinoma”. The results of the studies analyzed in this review support the benefits of targeted therapy in metastatic RCC. These include improved progression-free survival, overall survival, and quality of life as well as reduced toxicities compared to immunotherapy. The improvement in outcomes in metastatic RCC makes these drugs a preferred option as a primary treatment for these patients.
References
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12. Al-Marrawi MY, Rini B. Pazopanib for the treatment of renal cancer. Expert Opin Pharmacother. 2011;12(7):1171-89. Doi: http://dx.doi.org/10.1517/14656566.2011.571206
13. Vasudev NS, Larkin JM. Tyrosine kinase inhibitors in the treatment of advanced renal cell carcinoma: focus on pazopanib. Clin Med Insights Oncol. 2011;5:333-42. [Pubmed].
14. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061-8. Doi: http://dx.doi.org/10.1200/JCO.2009.23.9764
15. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722-31.
Doi: http://dx.doi.org/10.1056/NEJMoa1303989
16. Bukowski RM. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma. Front Oncol. 2012;2:13. Doi: http://dx.doi.org/10.3389/fonc.2012.00013
17. Keisner SV, Shah SR. Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011;71(4):443-54. [Pubmed]
18. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte 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. Doi: http://dx.doi.org/10.1016/S1470-2045(07)70285-1
19. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-9. Doi: http://dx.doi.org/10.1016/S0140-6736(11)61613-9
20. Carmichael C, Lau C, Josephson DY, Pal SK. Comprehensive overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma. Clin Adv Hematol Oncol. 2012;10(5):307-14. [Pubmed]
21. Sonpavde G, Hutson TE, Rini BI. Axitinib for renal cell carcinoma. Expert Opin Investig Drugs. 2008;17(5):741-8. Doi: http://dx.doi.org/10.1517/13543784.17.5.741
22. Sridhar SS, Mackenzie MJ, Hotte SJ, Mukherjee SD, Tannock IF, Murray N, et al. A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium. Invest New Drugs. 2013;31(4):1008-15. Doi: http://dx.doi.org/10.1007/s10637-013-9931-1
23. Mulders P, Hawkins R, Nathan P, de Jong I, Osanto S, Porfiri E, et al. Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised phase II study. Eur J Cancer. 2012;48(4):527-37. Doi: http://dx.doi.org/10.1016/j.ejca.2011.12.022
24. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144-50. Doi: http://dx.doi.org/10.1200/JCO.2009.26.7849
25. Trump DL. Commentary on "comparative effectiveness of axitinib vs. sorafenib in advanced renal cell carcinoma (AXIS): a randomized phase 3 trial." B.I. Rini, B. Escudier, P. Tomczak, A. Kaprin, C. Szczylik, T.E. Hutson, M.D. Michaelson, V.A. Gorbunova, M.E. Gore, I.G. Rusakov, S. Negrier, Y.C. Ou, D. Castellano, H.Y. Lim, H. Uemura, J. Tarazi, D. Cella, C. Chen, B. Rosbrook, S. Kim, R.J. Motzer: Lancet 2011;378:1931-9 [Epub;2011, November 4]. Urol Oncol. 2012;30(5):748. Doi: http://dx.doi.org/10.1016/j.urolonc.2012.06.009
26. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422-8. Doi: http://dx.doi.org/10.1200/JCO.2008.16.9847
27. Tang PA, Tsao MS, Moore MJ. A review of erlotinib and its clinical use. Expert Opin Pharmacother. 2006;7(2):177-93. Doi: http://dx.doi.org/10.1517/14656566.7.2.177
28. Hainsworth JD, Sosman JA, Spigel DR, Edwards DL, Baughman C, Greco A. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol. 2005;23(31):7889-96. Doi: http://dx.doi.org/10.1200/JCO.2005.01.8234
29. Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, 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. Doi: http://dx.doi.org/10.1200/JCO.2007.11.5154
30. Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, et al. Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib. Br J Cancer. 2010;103(6):796-801. Doi: http://dx.doi.org/10.1038/sj.bjc.6605868
31. Sonpavde G, Choueiri TK. Biomarkers: the next therapeutic hurdle in metastatic renal cell carcinoma. Br J Cancer. 2012;107(7):1009-16. Doi: http://dx.doi.org/10.1038/bjc.2012.399
32. Cho DC, Atkins MB. Future directions in renal cell carcinoma: 2011 and beyond. Hematol Oncol Clin North Am. 2011;25(4):917-35. Doi: http://dx.doi.org/10.1016/j.hoc.2011.05.001
33. Pinto Marin A, Redondo Sanchez A, Espinosa Arranz E, Zamora Auon P, Castelo Fernandez B, Gonzalez Baron M. mTOR pathway inhibition in renal cell carcinoma. Urol Oncol. 2012;30(4):356-61. Doi: http://dx.doi.org/10.1016/j.urolonc.2009.11.008
34. Amato R. Everolimus for the treatment of advanced renal cell carcinoma. Expert Opin Pharmacother. 2011;12(7):1143-55. Doi: http://dx.doi.org/10.1517/14656566.2011.571382
35. Hainsworth JD, Spigel DR, Burris HA, Waterhouse D, Clark BL, Whorf R. Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Clin Oncol. 2010;28(13):2131-6. Doi: http://dx.doi.org/10.1200/JCO.2009.26.3152
36. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, 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. Doi: http://dx.doi.org/10.1016/S0140-6736(08)61039-9
37. Voss MH, Molina AM, Motzer RJ. mTOR inhibitors in advanced renal cell carcinoma. Hematol Oncol Clin North Am. 2011;25(4):835-52. Doi: http://dx.doi.org/10.1016/j.hoc.2011.04.008
38. Motzer RJ, Hudes GR, Curti BD, McDermott DF, Escudier BJ, Negrier S, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol. 2007;25(25):3958-64. Doi: http://dx.doi.org/10.1200/JCO.2006.10.5916
39. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271-81.
Doi: http://dx.doi.org/10.1056/NEJMoa066838
40. Koh Y, Lim HY, Ahn JH, Lee JL, Rha SY, Kim YJ, et al. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Ann Oncol. 2013;24(4):1026-31.
Doi: http://dx.doi.org/10.1093/annonc/mds582
41. Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, et al. A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Eur Urol. 2012;62(6):1013-9.
Doi: http://dx.doi.org/10.1016/j.eururo.2012.06.043
42. Choueiri TK, Vaishampayan U, Rosenberg JE, Logan TF, Harzstark AL, Bukowski RM, et al. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol. 2013;31(2):181-6. Doi: http://dx.doi.org/10.1200/JCO.2012.43.3383
43. Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10(8):757-63. Doi: http://dx.doi.org/10.1016/S1470-2045(09)70162-7
44. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171(3):1071-6. Doi: http://dx.doi.org/10.1097/01.ju.0000110610.61545.ae
45. Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, et al. J Clin Oncol. 2014; 32(8); 760-7. Doi: http://dx.doi.org/10.1200/JCO.2013.50.3961
2. Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol. 2010;58(3):398-406.
Doi: http://dx.doi.org/10.1016/j.eururo.2010.06.032
3. Najjar YG, Rini BI. Novel agents in renal carcinoma: a reality check. Ther Adv Med Oncol. 2012;4(4):183-94. Doi: http://dx.doi.org/10.1177/1758834012443725
4. Stadler WM. Targeted agents for the treatment of advanced renal cell carcinoma. Cancer. 2005;104(11):2323-33. Doi: http://dx.doi.org/10.1002/cncr.21453
5. Berg WJ, Divgi CR, Nanus DM, Motzer RJ. Novel investigative approaches for advanced renal cell carcinoma. Semin Oncol. 2000;27(2):234-9. [Pubmed]
6. Dorff TB, Goldkorn A, Quinn DI. Targeted therapy in renal cancer. Ther Adv Med Oncol. 2009;1(3):183-205. Doi: http://dx.doi.org/10.1177/1758834009349119
7. Coppin C, Porzsolt F, Awa A, Kumpf J, Coldman A, Wilt T. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2005(1):CD001425. [Pubmed]
8. Rak J, Kerbel RS. Ras regulation of vascular endothelial growth factor and angiogenesis. Methods Enzymol. 2001;333:267-83. Doi: http://dx.doi.org/10.1016/S0076-6879(01)33062-8
9. Hilger RA, Scheulen ME, Strumberg D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie. 2002;25(6):511-8. Doi: http://dx.doi.org/10.1159/000068621
10. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, 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. Doi: http://dx.doi.org/10.1200/JCO.2005.03.6723
11. Vakkalanka BK, Bukowski RM. Novel drugs for renal cell carcinoma. Expert Opin Investig Drugs. 2008;17(10):1501-16. Doi: http://dx.doi.org/10.1517/13543784.17.10.1501
12. Al-Marrawi MY, Rini B. Pazopanib for the treatment of renal cancer. Expert Opin Pharmacother. 2011;12(7):1171-89. Doi: http://dx.doi.org/10.1517/14656566.2011.571206
13. Vasudev NS, Larkin JM. Tyrosine kinase inhibitors in the treatment of advanced renal cell carcinoma: focus on pazopanib. Clin Med Insights Oncol. 2011;5:333-42. [Pubmed].
14. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061-8. Doi: http://dx.doi.org/10.1200/JCO.2009.23.9764
15. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722-31.
Doi: http://dx.doi.org/10.1056/NEJMoa1303989
16. Bukowski RM. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma. Front Oncol. 2012;2:13. Doi: http://dx.doi.org/10.3389/fonc.2012.00013
17. Keisner SV, Shah SR. Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011;71(4):443-54. [Pubmed]
18. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte 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. Doi: http://dx.doi.org/10.1016/S1470-2045(07)70285-1
19. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-9. Doi: http://dx.doi.org/10.1016/S0140-6736(11)61613-9
20. Carmichael C, Lau C, Josephson DY, Pal SK. Comprehensive overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma. Clin Adv Hematol Oncol. 2012;10(5):307-14. [Pubmed]
21. Sonpavde G, Hutson TE, Rini BI. Axitinib for renal cell carcinoma. Expert Opin Investig Drugs. 2008;17(5):741-8. Doi: http://dx.doi.org/10.1517/13543784.17.5.741
22. Sridhar SS, Mackenzie MJ, Hotte SJ, Mukherjee SD, Tannock IF, Murray N, et al. A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium. Invest New Drugs. 2013;31(4):1008-15. Doi: http://dx.doi.org/10.1007/s10637-013-9931-1
23. Mulders P, Hawkins R, Nathan P, de Jong I, Osanto S, Porfiri E, et al. Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised phase II study. Eur J Cancer. 2012;48(4):527-37. Doi: http://dx.doi.org/10.1016/j.ejca.2011.12.022
24. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144-50. Doi: http://dx.doi.org/10.1200/JCO.2009.26.7849
25. Trump DL. Commentary on "comparative effectiveness of axitinib vs. sorafenib in advanced renal cell carcinoma (AXIS): a randomized phase 3 trial." B.I. Rini, B. Escudier, P. Tomczak, A. Kaprin, C. Szczylik, T.E. Hutson, M.D. Michaelson, V.A. Gorbunova, M.E. Gore, I.G. Rusakov, S. Negrier, Y.C. Ou, D. Castellano, H.Y. Lim, H. Uemura, J. Tarazi, D. Cella, C. Chen, B. Rosbrook, S. Kim, R.J. Motzer: Lancet 2011;378:1931-9 [Epub;2011, November 4]. Urol Oncol. 2012;30(5):748. Doi: http://dx.doi.org/10.1016/j.urolonc.2012.06.009
26. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422-8. Doi: http://dx.doi.org/10.1200/JCO.2008.16.9847
27. Tang PA, Tsao MS, Moore MJ. A review of erlotinib and its clinical use. Expert Opin Pharmacother. 2006;7(2):177-93. Doi: http://dx.doi.org/10.1517/14656566.7.2.177
28. Hainsworth JD, Sosman JA, Spigel DR, Edwards DL, Baughman C, Greco A. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol. 2005;23(31):7889-96. Doi: http://dx.doi.org/10.1200/JCO.2005.01.8234
29. Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, 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. Doi: http://dx.doi.org/10.1200/JCO.2007.11.5154
30. Flaig TW, Costa LJ, Gustafson DL, Breaker K, Schultz MK, Crighton F, et al. Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib. Br J Cancer. 2010;103(6):796-801. Doi: http://dx.doi.org/10.1038/sj.bjc.6605868
31. Sonpavde G, Choueiri TK. Biomarkers: the next therapeutic hurdle in metastatic renal cell carcinoma. Br J Cancer. 2012;107(7):1009-16. Doi: http://dx.doi.org/10.1038/bjc.2012.399
32. Cho DC, Atkins MB. Future directions in renal cell carcinoma: 2011 and beyond. Hematol Oncol Clin North Am. 2011;25(4):917-35. Doi: http://dx.doi.org/10.1016/j.hoc.2011.05.001
33. Pinto Marin A, Redondo Sanchez A, Espinosa Arranz E, Zamora Auon P, Castelo Fernandez B, Gonzalez Baron M. mTOR pathway inhibition in renal cell carcinoma. Urol Oncol. 2012;30(4):356-61. Doi: http://dx.doi.org/10.1016/j.urolonc.2009.11.008
34. Amato R. Everolimus for the treatment of advanced renal cell carcinoma. Expert Opin Pharmacother. 2011;12(7):1143-55. Doi: http://dx.doi.org/10.1517/14656566.2011.571382
35. Hainsworth JD, Spigel DR, Burris HA, Waterhouse D, Clark BL, Whorf R. Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Clin Oncol. 2010;28(13):2131-6. Doi: http://dx.doi.org/10.1200/JCO.2009.26.3152
36. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, 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. Doi: http://dx.doi.org/10.1016/S0140-6736(08)61039-9
37. Voss MH, Molina AM, Motzer RJ. mTOR inhibitors in advanced renal cell carcinoma. Hematol Oncol Clin North Am. 2011;25(4):835-52. Doi: http://dx.doi.org/10.1016/j.hoc.2011.04.008
38. Motzer RJ, Hudes GR, Curti BD, McDermott DF, Escudier BJ, Negrier S, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol. 2007;25(25):3958-64. Doi: http://dx.doi.org/10.1200/JCO.2006.10.5916
39. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271-81.
Doi: http://dx.doi.org/10.1056/NEJMoa066838
40. Koh Y, Lim HY, Ahn JH, Lee JL, Rha SY, Kim YJ, et al. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Ann Oncol. 2013;24(4):1026-31.
Doi: http://dx.doi.org/10.1093/annonc/mds582
41. Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, et al. A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Eur Urol. 2012;62(6):1013-9.
Doi: http://dx.doi.org/10.1016/j.eururo.2012.06.043
42. Choueiri TK, Vaishampayan U, Rosenberg JE, Logan TF, Harzstark AL, Bukowski RM, et al. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol. 2013;31(2):181-6. Doi: http://dx.doi.org/10.1200/JCO.2012.43.3383
43. Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10(8):757-63. Doi: http://dx.doi.org/10.1016/S1470-2045(09)70162-7
44. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171(3):1071-6. Doi: http://dx.doi.org/10.1097/01.ju.0000110610.61545.ae
45. Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, et al. J Clin Oncol. 2014; 32(8); 760-7. Doi: http://dx.doi.org/10.1200/JCO.2013.50.3961
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Targeted Therapy for Metastatic Renal Carcinoma: an Update. (2014). Journal of Kidney Cancer, 1(6), 63-73. https://doi.org/10.15586/jkcvhl.2014.14
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Kidney Cancer: Review Articles
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Targeted Therapy for Metastatic Renal Carcinoma: an Update. (2014). Journal of Kidney Cancer, 1(6), 63-73. https://doi.org/10.15586/jkcvhl.2014.14