Renal cell carcinoma medical therapy: Difference between revisions

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{{CMG}}
__NOTOC__
{{Renal cell carcinoma}}
{{Renal cell carcinoma}}
{{CMG}} {{AE}} {{F.K}}
==Overview==
==Overview==
If the tumor is confined to the kidneys (occurs in about 40% of cases), then RCC can be treated roughly 90% of the time with [[surgery]]. If RCC has spread outside of the kidneys, often into the [[lymph nodes]] or the main vein of the kidney, then it is often treated with [[chemotherapy]] and other treatments.
The medical therapies of renal cell carcinoma include [[chemotherapy]], [[hormone treatment]], [[immunotherapy]], and [[targeted therapy]].


==Therapies==
==Medical Therapy==
===Watchful waiting===
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.


Small renal tumors represent the majority of tumors that are treated today by way of partial [[nephrectomy]]. The average growth of these masses is about 4-5 mm per year, and a significant proportion (up to 40%) of tumors less than 4cm in diameter are benign. More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation. In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3-5 cm, beyond which the risk of distant spread (metastases) is about 5%.
In summary, the following table shows the response rate of various treatment options for renal cell carcinoma:
{| style="border-collapse:collapse; text-align:left;" cellpadding="5" border="1" align="center"
|+ '''''Summary of Medical Therapy for Metastatic Renal Cell Carcinoma<ref name="pmid19269025">{{cite journal| author=Rini BI, Campbell SC, Escudier B| title=Renal cell carcinoma. | journal=Lancet | year= 2009 | volume= 373 | issue= 9669 | pages= 1119-32 |pmid=19269025 | doi=10.1016/S0140-6736(09)60229-4 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19269025  }} </ref>'''''


===Percutaneous therapies===
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |'''Objective Response Rate'''
|-
| bgcolor="#ececec" |'''Hormone Treatment<ref name="pmid10023944">{{cite journal| author=|title=Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. |journal=Lancet | year= 1999 | volume= 353 | issue= 9146 | pages= 14-7 | pmid=10023944 | doi=| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023944  }} </ref>''' || 2%
|-
| bgcolor="#ececec" |'''Chemotherapy<ref name="pmid7855619">{{cite journal| author=Yagoda A, Abi-Rached B, Petrylak D| title=Chemotherapy for advanced renal-cell carcinoma: 1983-1993. |journal=Semin Oncol | year= 1995 | volume= 22 | issue= 1 | pages= 42-60 | pmid=7855619 | doi=| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7855619  }} </ref><ref name="pmid10647643">{{cite journal| author=Motzer RJ, Russo P| title=Systemic therapy for renal cell carcinoma. | journal=J Urol | year= 2000 | volume= 163 | issue= 2 | pages= 408-17| pmid=10647643 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10647643  }} </ref>''' || 5-6&
|-
| bgcolor="#ececec" |'''Aldesleukin (IL2)<ref name="pmid15625368">{{cite journal|author=McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF et al.|title=Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. | journal=J Clin Oncol |year= 2005 | volume= 23 | issue= 1 | pages= 133-41 | pmid=15625368 |doi=10.1200/JCO.2005.03.206 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15625368  }} </ref><ref name="pmid12915604">{{cite journal| author=Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P et al.| title=Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. | journal=J Clin Oncol | year= 2003 |volume= 21 | issue= 16 | pages= 3127-32 | pmid=12915604 | doi=10.1200/JCO.2003.02.122 |pmc=PMC2275327 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12915604  }} </ref>''' ||21-23% at high dose<br>10% at low dose
|-
| bgcolor="#ececec" |'''Interferon alfa<ref name="pmid10023944">{{cite journal| author=|title=Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. |journal=Lancet | year= 1999 | volume= 353 | issue= 9146 | pages= 14-7 | pmid=10023944 | doi=| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023944  }} </ref><ref name="pmid10561363">{{cite journal| author=Pyrhönen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T et al.| title=Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. | journal=J Clin Oncol | year= 1999 | volume= 17 | issue= 9 | pages= 2859-67 | pmid=10561363 | doi= |pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10561363  }} </ref><ref name="pmid7459811">{{cite journal| author=Miller AB, Hoogstraten B, Staquet M, Winkler A|title=Reporting results of cancer treatment. | journal=Cancer | year= 1981 | volume= 47 |issue= 1 | pages= 207-14 | pmid=7459811 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7459811  }} </ref>''' || 10-15%
|-
| bgcolor="#ececec" |'''Sunitinib<ref name="pmid16330672">{{cite journal| author=Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA et al.| title=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. | journal=J Clin Oncol | year= 2006 | volume= 24 | issue= 1 | pages= 16-24 | pmid=16330672 |doi=10.1200/JCO.2005.02.2574 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16330672  }} </ref><ref name="pmid16757724">{{cite journal| author=Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR et al.| title=Sunitinib in patients with metastatic renal cell carcinoma. |journal=JAMA | year= 2006 | volume= 295 | issue= 21 | pages= 2516-24 | pmid=16757724 |doi=10.1001/jama.295.21.2516 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16757724  }} </ref><ref name="pmid17215529">{{cite journal| author=Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et al.| title=Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 2 | pages= 115-24 |pmid=17215529 | doi=10.1056/NEJMoa065044 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17215529  }} </ref>''' ||30-45%
|-
| bgcolor="#ececec" |'''Sorafenib<ref name="pmid17215530">{{cite journal| author=Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M et al.| title=Sorafenib in advanced clear-cell renal-cell carcinoma. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 2| pages= 125-34 | pmid=17215530 | doi=10.1056/NEJMoa060655 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17215530  }} </ref><ref name="pmid19171708">{{cite journal| author=Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F et al.| title=Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. |journal=J Clin Oncol | year= 2009 | volume= 27 | issue= 8 | pages= 1280-9 | pmid=19171708 |doi=10.1200/JCO.2008.19.3342 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19171708  }} </ref>''' ||30-45%
|-
| bgcolor="#ececec" |'''Bevacizumab<ref name="pmid18156031">{{cite journal| author=Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C et al.| title=Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. | journal=Lancet | year= 2007 | volume= 370 | issue= 9605 | pages= 2103-11 | pmid=18156031 | doi=10.1016/S0140-6736(07)61904-7 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18156031  }} </ref><ref name="pmid18936475">{{cite journal| author=Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS et al.| title=Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 33 | pages= 5422-8 | pmid=18936475 |doi=10.1200/JCO.2008.16.9847 | pmc=PMC2651074 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18936475  }} </ref><ref name="pmid12890841">{{cite journal| author=Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL et al.| title=A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 5 | pages= 427-34 | pmid=12890841 |doi=10.1056/NEJMoa021491 | pmc=PMC2275324 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12890841  }} </ref>''' ||30-45%
|-
| bgcolor="#ececec" |'''Temsirolimus<ref name="pmid14990647">{{cite journal| author=Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR et al.| title=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. | journal=J Clin Oncol | year= 2004 | volume= 22 | issue= 5 | pages= 909-18 | pmid=14990647 | doi=10.1200/JCO.2004.08.185 |pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14990647  }} </ref><ref name="pmid17538086">{{cite journal| author=Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A et al.| title=Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 22 | pages= 2271-81 |pmid=17538086 | doi=10.1056/NEJMoa066838 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17538086  }} </ref>''' ||30-45%
|}
<sup><center>Adapted from Rini BI, Campbell SC, and Escudier B. Renal cell carcinoma.''Lancet''.2009; 373(9669):1119-32.</center></sup>


[[Percutaneous]], image-guided therapies, usually managed by [[radiologists]], are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by [[computed tomography]], [[ultrasound]], or even [[magnetic resonance imaging]] guidance, and then destroying the tumor with heat ([[radiofrequency ablation]]) or cold ([[cryotherapy]]).  These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible.
===Immunotherapy===
Immunotherapy is considered the first line therapy for patients with metastatic renal cell carcinoma.<ref name="pmid15897568">{{cite journal| author=Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A et al.| title=Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. | journal=Clin Cancer Res | year= 2005 |volume= 11 | issue= 10 | pages= 3714-21 | pmid=15897568 | doi=10.1158/1078-0432.CCR-04-2019 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15897568  }} </ref><ref name="pmid12576453">{{cite journal| author=Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y et al.| title=Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. |journal=Clin Cancer Res | year= 2003 | volume= 9 | issue= 2 | pages= 802-11 |pmid=12576453 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12576453  }} </ref><ref name="pmid16113605">{{cite journal| author=Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB| title=Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. | journal=J Immunother | year= 2005 | volume= 28 | issue= 5 | pages= 488-95 | pmid=16113605 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16113605  }}</ref><ref name="pmid15625368">{{cite journal| author=McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF et al.| title=Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. |journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 1 | pages= 133-41 |pmid=15625368 | doi=10.1200/JCO.2005.03.206 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15625368  }} </ref><ref name="pmid12915604">{{cite journal| author=Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P et al.| title=Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. | journal=J Clin Oncol | year= 2003 | volume= 21 | issue= 16 | pages= 3127-32 | pmid=12915604 |doi=10.1200/JCO.2003.02.122 | pmc=PMC2275327 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12915604  }}</ref><ref name="pmid9562581">{{cite journal| author=Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C et al.| title=Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie. | journal=N Engl J Med | year= 1998 | volume= 338 | issue= 18| pages= 1272-8 | pmid=9562581 | doi=10.1056/NEJM199804303381805 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9562581  }} </ref>
*Aldesleukin (IL2)
**It is considered as a preferable option for patients with good cardiovascular performance status.
**It is associated with [[capillary leak syndrome]].
*Interferon Alfa
**It is beneficial in renal cell carcinoma, particularly when combined with [[aldesleukin]].
*[[Nivolumab]] plus [[ipilimumab]]  
*[[Pembrolizumab]]
*[[Atezolizumab]]


===Radiation therapy===
===Targeted therapy===
====VEGF Neutralizing Antibody====
=====Sunitinib Malate=====
*Sunitinib malate is a [[tyrosine kinase inhibitor]] of VEGF receptors considered as first line therapy.<ref name="pmid12538485">{{cite journal| author=Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G et al.| title=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. | journal=Clin Cancer Res | year= 2003 |volume= 9 | issue= 1 | pages= 327-37 | pmid=12538485 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12538485  }}</ref>
*Sunitinib has been studied compare to interferon and has shown advantage in both survival and response rate.<ref name="pmid16330672">{{cite journal| author=Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA et al.| title=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. |journal=J Clin Oncol | year= 2006 | volume= 24 | issue= 1 | pages= 16-24 | pmid=16330672| doi=10.1200/JCO.2005.02.2574 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16330672  }} </ref><ref name="pmid16757724">{{cite journal| author=Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR et al.| title=Sunitinib in patients with metastatic renal cell carcinoma. | journal=JAMA | year= 2006 | volume= 295 | issue= 21 | pages= 2516-24 |pmid=16757724 | doi=10.1001/jama.295.21.2516 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16757724  }} </ref><ref name="pmid17215529">{{cite journal| author=Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et al.| title=Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 2 |pages= 115-24 | pmid=17215529 | doi=10.1056/NEJMoa065044 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17215529  }}</ref>
*Associated toxicity includes [[fatigue]], [[hand-foot syndrome]], [[diarrhea]], [[hypertension]], [[hypothyroidism]], and decreased [[left ventricular function]].<ref name="pmid17202116">{{cite journal| author=Rini BI, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L et al.|title=Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. | journal=J Natl Cancer Inst | year= 2007 | volume= 99 | issue= 1 | pages= 81-3 | pmid=17202116 | doi=10.1093/jnci/djk008 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17202116  }} </ref><ref name="pmid18083403">{{cite journal| author=Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L et al.| title=Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. | journal=Lancet | year= 2007 | volume= 370 | issue= 9604 | pages= 2011-9 | pmid=18083403 | doi=10.1016/S0140-6736(07)61865-0 | pmc=PMC2643085 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18083403  }} </ref><ref name="pmid18386829">{{cite journal| author=Khakoo AY, Kassiotis CM, Tannir N, Plana JC, Halushka M, Bickford C et al.| title=Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. | journal=Cancer | year= 2008 |volume= 112 | issue= 11 | pages= 2500-8 | pmid=18386829 | doi=10.1002/cncr.23460 | pmc=| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18386829  }} </ref>


[[Radiation therapy]] is not commonly used for treatment of renal cell carcinoma because it is usually not successful. Radiation therapy may be used to palliate the symptoms of skeletal metastases.
=====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.<ref name="pmid17215530">{{cite journal|author=Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M et al.|title=Sorafenib in advanced clear-cell renal-cell carcinoma. | journal=N Engl J Med |year= 2007 | volume= 356 | issue= 2 | pages= 125-34 | pmid=17215530 |doi=10.1056/NEJMoa060655 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17215530  }}</ref>
*Associated toxicity includes those of [[sunitinib]] but at a lesser rate.


===Medications===
====Bevacizumab====
*Monoclonal antibody against VEGF considered first line therapy in Europe.<ref name="pmid9377574">{{cite journal| author=Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L et al.| title=Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. |journal=Cancer Res | year= 1997 | volume= 57 | issue= 20 | pages= 4593-9 | pmid=9377574| doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9377574  }} </ref><ref name="pmid19269025">{{cite journal| author=Rini BI, Campbell SC, Escudier B| title=Renal cell carcinoma. | journal=Lancet | year= 2009 | volume= 373 | issue= 9669 | pages= 1119-32 | pmid=19269025 | doi=10.1016/S0140-6736(09)60229-4 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19269025  }}</ref>
*Response rate and progression free survival are both increased with combination with inferferon.<ref name="pmid18156031">{{cite journal| author=Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C et al.| title=Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. | journal=Lancet | year= 2007 | volume= 370 | issue= 9605 | pages= 2103-11 | pmid=18156031 | doi=10.1016/S0140-6736(07)61904-7 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18156031  }}</ref>
*Toxicity includes fatigue, [[anorexia]], [[hypertension]], and [[proteinuria]].<ref name="pmid19269025">{{cite journal| author=Rini BI, Campbell SC, Escudier B| title=Renal cell carcinoma. | journal=Lancet | year= 2009 | volume= 373 | issue= 9669 | pages= 1119-32 | pmid=19269025 | doi=10.1016/S0140-6736(09)60229-4 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19269025  }} </ref>


RCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions." This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and [[interleukin-2]] (IL-2), to reproduce this response. IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. [[Bevacizumab]], an antibody to [[VEGF]], has significantly prolonged time to progression, but phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.<ref>{{cite journal |author=Michaelson MD, Iliopoulos O, McDermott DF, McGovern FJ, Harisinghani MG, Oliva E |title=Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma |journal=N Engl J Med. |volume=358 |issue=22 |pages=2389–96 |year=2008 |month=May |pmid=18509125 |doi=10.1056/NEJMcpc0802449 |url=http://content.nejm.org/cgi/content/full/358/22/2389}}</ref>
=====EGFR-Neutralizing Antibody=====
[[Epidermal growth factor receptors|Epidermal growth factor receptor]] (EGFR) inhibitors are used less frequently than VEGF inhibitors. Examples of EGFR inhibitors are listed below<ref name="pmid16339096">{{cite journal| author=Cohen HT, McGovern FJ| title=Renal-cell carcinoma. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 23 | pages= 2477-90 | pmid=16339096 | doi=10.1056/NEJMra043172 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16339096  }} </ref>:
*[[Panitumumab]]
*[[Gefitinib]]
*[[Erlotinib]]


[[Sorafenib]] was FDA approved in December 2005 for treatment of advanced renal cell cancer, the first receptor tyrosine [[kinase]] (RTK) inhibitor indicated for this use.
===mTOR Inhibitors===
 
====Temsirolimus====
A month later, [[Sunitinib]] was approved as well. Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting [[angiogenesis]] as well as tumor cell proliferation. Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib. However, these agents have not been directly compared against one another in a single trial. [http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sunitinib][http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sorafenib]
*[[Temsirolimus]] (CCI-779) is often reserved only for high risk patients with metastatic disease.
 
*[[Temsirolimus]] monotherapy is regarded as superior to interferon monotherapy with no additional advantage in combination therapy of both drugs.<ref name="pmid10561319">{{cite journal| author=Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J|title=Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. | journal=J Clin Oncol | year= 1999 | volume= 17 | issue= 8 | pages= 2530-40| pmid=10561319 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10561319  }} </ref><ref name="pmid15681528">{{cite journal| author=Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P et al.| title=Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. | journal=J Clin Oncol | year= 2005 | volume= 23 |issue= 4 | pages= 832-41 | pmid=15681528 | doi=10.1200/JCO.2005.05.179 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15681528  }}</ref>
Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the ''[[New England Journal of Medicine]]''. This study showed that [[Sunitinib]] offered superior efficacy compared with [[interferon-α]]. Progression-free survival (primary endpoint) was more than doubled. The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α. Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa. <ref name=motzer>{{cite journal | author = Motzer RJ ''et al.'' | title = Sunitinib versus interferon alfa in metastatic renal-cell carcinoma | journal = [[New England Journal of Medicine|N Engl J Med]] | volume = 356 | issue = 2 | pages = 115–124 | year = 2007 | pmid = 17215529 | doi = 10.1056/NEJMoa065044}} </ref> Based on these results, lead investigator Dr. Robert Motzer announced at ASCO 2006 that “Sunitinib is the new reference standard for the first-line treatment of mRCC.” <ref name=motzer2>{{cite conference
*Toxicity includes [[anemia]], [[asthenia]], [[dyspnea]], [[dyslipidemia]], and [[hyperglycemia]]. New studies have shown added benefit when [[temsirolimus]] is combined with everolimus.<ref name="pmid18653228">{{cite journal| author=Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S et al.| title=Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. |journal=Lancet | year= 2008 | volume= 372 | issue= 9637 | pages= 449-56 | pmid=18653228| doi=10.1016/S0140-6736(08)61039-9 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18653228  }} </ref>
|author=Motzer RJ ''et al.'' | title=Phase 3 Randomized Trial of Sunitinib malate (SU11248) versus Interferon-alfa as First-line Systemic Therapy for Patients with Metastatic Renal Cell Carcinoma |booktitle=ASCO 2006 |url=http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=40&index=y&abstractID=30512}} </ref>
 
Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mamallian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features. The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www.ASCO.org).


===Chemotherapy===
===Chemotherapy===
*[[Gemcitabine]]/[[Fluorouracil]]
**Use of chemotherapy, such as [[gemcitabine]]/[[fluorouracil]] is low in renal cell carcinoma.<ref name="pmid10856102">{{cite journal| author=Rini BI, Vogelzang NJ, Dumas MC, Wade JL, Taber DA, Stadler WM| title=Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. | journal=J Clin Oncol | year= 2000 | volume= 18 | issue= 12 | pages= 2419-26 | pmid=10856102 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10856102}}</ref>
**Combination of both chemotherapeutic agents yield better response rates than either alone.


[[Chemotherapy]] may be used in some cases, but cure is unlikely unless all the cancer can be removed with surgery. The use of Tyrosine Kinase (TK) inhibitors, such as [[Sunitinib]] and [[Sorafenib]], and [[Temsirolimus]] are described in a different section.
*Vinblastine
 
**[[Vinblastine]] has shown to be ineffective in metastatic renal cell carcinoma.<ref name="pmid1524914">{{cite journal| author=Fosså SD, Droz JP, Pavone-Macaluso MM, Debruyne FJ, Vermeylen K, Sylvester R| title=Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group. | journal=Eur J Cancer | year= 1992 | volume= 28A | issue= 4-5 | pages= 878-80 | pmid=1524914 | doi= |pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1524914  }} </ref>
===Vaccine===
**Combination with other agents has not shown added benefit either.<ref name="pmid2016626">{{cite journal| author=Neidhart JA, Anderson SA, Harris JE, Rinehart JJ, Laszlo J, Dexeus FH et al.| title=Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases. | journal=J Clin Oncol | year= 1991 |volume= 9 | issue= 5 | pages= 832-6 | pmid=2016626 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2016626  }}</ref>
 
In November 2006, it was announced that a [[vaccine]] had been developed and tested with very promising results.(See [http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770]) The new vaccine, called [[TroVax]], works by harnessing the patient's own immune system to fight the disease. Oxford BioMedica[http://www.oxfordbiomedica.co.uk/]. Further vaccine trials are underway.


===Cryoablation===
===Hormone Therapy===
===Medroxyprogesterone===
*Large randomized trials did not yield high responses as anti-tumor effects when used alone or when used with other medications.<ref name="pmid1524914">{{cite journal| author=Fosså SD, Droz JP, Pavone-Macaluso MM, Debruyne FJ, Vermeylen K, Sylvester R| title=Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group. | journal=Eur J Cancer | year= 1992 | volume= 28A | issue= 4-5 | pages= 878-80 | pmid=1524914 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1524914  }} </ref><ref name="pmid2016626">{{cite journal| author=Neidhart JA, Anderson SA, Harris JE, Rinehart JJ, Laszlo J, Dexeus FH et al.| title=Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases. | journal=J Clin Oncol | year= 1991 | volume= 9 | issue= 5 | pages= 832-6 | pmid=2016626 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2016626  }} </ref>
*Their role is reserved for [[palliative care]].<ref name="pmid10023944">{{cite journal| author=| title=Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. | journal=Lancet | year= 1999 |volume= 353 | issue= 9146 | pages= 14-7 | pmid=10023944 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023944  }} </ref><ref name="pmid7855619">{{cite journal| author=Yagoda A, Abi-Rached B, Petrylak D|title=Chemotherapy for advanced renal-cell carcinoma: 1983-1993. | journal=Semin Oncol |year= 1995 | volume= 22 | issue= 1 | pages= 42-60 | pmid=7855619 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7855619  }} </ref><ref name="pmid10647643">{{cite journal| author=Motzer RJ, Russo P| title=Systemic therapy for renal cell carcinoma. | journal=J Urol | year= 2000 | volume= 163 | issue= 2 |pages= 408-17 | pmid=10647643 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10647643  }} </ref>


This involves destroying the kidney tumor without surgery, by freezing the tumor.  The process can remove 95% of tumors in one treatment and can be tolerated by patients who are not good candidates for surgery (older or weak patients). <ref> <http://www.yourcancertoday.com/news/drnakada.html" title=" Dr. Nakada, on Your Cancer Today</ref>.
The outcome varies depending on the size of the tumor, whether it is confined to the kidney or not, and the presence or absence of metastatic spread. The Fuhrman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.
The [[five year survival rate]] is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.
For those that have tumor recurrence after surgery, the prognosis is generally poor.  Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Kidney diseases]]
[[Category:Types of cancer]]
[[Category:Nephrology]]
[[Category:Mature chapter]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Nephrology]]
[[Category:Surgery]]

Latest revision as of 14:52, 5 December 2018

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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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