Difference between revisions of "Renal cell carcinoma"

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=Metastatic disease=
 
=Metastatic disease=
 
==Axitinib (Inlyta)==
 
==Axitinib (Inlyta)==
 +
Level of Evidence:
 +
<span
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style="background:#00CD00;
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padding:3px 6px 3px 6px;
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border-color:black;
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border-width:2px;
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border-style:solid;">Phase III</span>
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===Regimen, Rini, et al. 2011 (AXIS) & Motzer, et al. 2013 (AXIS)===
 
===Regimen, Rini, et al. 2011 (AXIS) & Motzer, et al. 2013 (AXIS)===
 
*[[Axitinib (Inlyta)]] 5 mg PO BID x at least 2 weeks
 
*[[Axitinib (Inlyta)]] 5 mg PO BID x at least 2 weeks
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===References===
 
===References===
 
# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
 
# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
−
# Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 Apr 15. pii: S1470-2045(13)70093-7. doi: 10.1016/S1470-2045(13)70093-7. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S1470204513700937 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23598172 PubMed]
+
# '''Update:''' Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 Apr 15. pii: S1470-2045(13)70093-7. doi: 10.1016/S1470-2045(13)70093-7. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S1470204513700937 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23598172 PubMed]
  
 
==Bevacizumab (Avastin)==
 
==Bevacizumab (Avastin)==
 
===Regimen, Bukowski, et al. 2007===
 
===Regimen, Bukowski, et al. 2007===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
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padding:3px 6px 3px 6px;
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border-color:black;
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border-width:2px;
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border-style:solid;">Randomized Phase II, >20 per arm</span>
 +
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes (can subsequently be reduced to 60 and 30 minute infusions as tolerated) once every 2 weeks
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes (can subsequently be reduced to 60 and 30 minute infusions as tolerated) once every 2 weeks
 +
 +
'''given for up to 104 weeks, until progression of disease, or unacceptable toxicity'''
 +
 +
===References===
 +
# Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. Epub 2007 Sep 17. [http://jco.ascopubs.org/content/25/29/4536.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17876014 PubMed]
 +
 +
==Bevacizumab & Erlotinib==
 +
===Regimen, Bukowski, et al. 2007===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, >20 per arm</span>
 +
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes (can subsequently be reduced to 60 and 30 minute infusions as tolerated) once every 2 weeks
 +
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
  
 
'''given for up to 104 weeks, until progression of disease, or unacceptable toxicity'''
 
'''given for up to 104 weeks, until progression of disease, or unacceptable toxicity'''
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==Bevacizumab & Interferon alfa-2a==
 
==Bevacizumab & Interferon alfa-2a==
−
===Regimen, Escudier, et al. 2010 (AVOREN)===
+
===Regimen, Escudier, et al. 2007 (AVOREN)===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
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===References===
 
===References===
−
# Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2144.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368553 PubMed]
+
# Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. [http://www.ncbi.nlm.nih.gov/pubmed/18156031 PubMed]
 +
# Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. doi: 10.1200/JCO.2008.16.9847. Epub 2008 Oct 20. [http://jco.ascopubs.org/content/26/33/5422.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18936475 PubMed]
 +
# '''Update:''' Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2144.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368553 PubMed]
 +
# '''Update:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010 May 1;28(13):2137-43. doi: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2137.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20368558 PubMed]
  
 
==Erlotinib (Tarceva)==
 
==Erlotinib (Tarceva)==
 
===Regimen, Gordon, et al. 2009 (SWOG S0317)===
 
===Regimen, Gordon, et al. 2009 (SWOG S0317)===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Erlotinib (Tarceva)]] 150 mg PO once per day, given 1 hour before or 2 hours after meals
 
*[[Erlotinib (Tarceva)]] 150 mg PO once per day, given 1 hour before or 2 hours after meals
  
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==Everolimus (Afinitor)==
 
==Everolimus (Afinitor)==
−
===Regimen, Motzer, et al. 2008 (RECORD-1) & Motzer, et al. 2010 (RECORD-1)===
+
===Regimen, Motzer, et al. 2008 (RECORD-1)===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
**Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
 
**Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
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===References===
 
===References===
 
# Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18653228 PubMed]
 
# Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18653228 PubMed]
−
# Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20549832 PubMed]
+
# '''Update:''' Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20549832 PubMed]
  
 
==Gemcitabine & Doxorubicin==
 
==Gemcitabine & Doxorubicin==
 
===Regimen, Roubaud, et al. 2011 & Haas, et al. 2012 (ECOG 8802)===
 
===Regimen, Roubaud, et al. 2011 & Haas, et al. 2012 (ECOG 8802)===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Gemcitabine (Gemzar)]] 1500 mg/m2 IV over 30 minutes once on day 1
 
*[[Gemcitabine (Gemzar)]] 1500 mg/m2 IV over 30 minutes once on day 1
 
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV push once on day 1
 
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV push once on day 1
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==Gemcitabine & Sunitinib==
 
==Gemcitabine & Sunitinib==
 
===Regimen, Pandya, et al. 2011===
 
===Regimen, Pandya, et al. 2011===
 +
Level of Evidence:
 +
<span
 +
style="background:#ff0000;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Retrospective</span>
 +
 
*[[Gemcitabine (Gemzar)]] 750 mg/m2 IV over 90 minutes once per day on days 1 & 8
 
*[[Gemcitabine (Gemzar)]] 750 mg/m2 IV over 90 minutes once per day on days 1 & 8
 
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 2 to 15
 
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 2 to 15
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===Regimen #1, McDermott, et al. 2005===
 
===Regimen #1, McDermott, et al. 2005===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 600,000 units/kg IV every 8 hours x up to 14 doses per week, on days 1 to 5, 15 to 19
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 600,000 units/kg IV every 8 hours x up to 14 doses per week, on days 1 to 5, 15 to 19
  
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===Regimen #2, Yang, et al. 2003===
 
===Regimen #2, Yang, et al. 2003===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses
 
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses is given again  
 
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 15 doses is given again  
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===Regimen #3, Klapper, et al. 2008===
 
===Regimen #3, Klapper, et al. 2008===
 +
Level of Evidence:
 +
<span
 +
style="background:#ff0000;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Retrospective</span>
 +
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses (reduced from originally up to 15 doses due to few patients tolerating 15 doses)
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses (reduced from originally up to 15 doses due to few patients tolerating 15 doses)
 
**Then after 10 to 15 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses is given again  
 
**Then after 10 to 15 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 720,000 units/kg IV every 8 hours x up to 12 doses is given again  
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==Low-dose (LD) IL-2==
 
==Low-dose (LD) IL-2==
 
===Regimen, Yang, et al. 2003===
 
===Regimen, Yang, et al. 2003===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses
 
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses is given again  
 
**Then after 7 to 10 days of rest, [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 72,000 units/kg IV every 8 hours x up to 15 doses is given again  
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==Subcutaneous IL-2==
 
==Subcutaneous IL-2==
 
===Regimen, Yang, et al. 2003===
 
===Regimen, Yang, et al. 2003===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC once per day x 5 days on week 1
 
*[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC once per day x 5 days on week 1
 
**Then [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 125,000 units/kg SC once per day x 5 days per week during weeks 2 to 6
 
**Then [[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 125,000 units/kg SC once per day x 5 days per week during weeks 2 to 6
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==Interferon alfa-2a (Roferon-A)==
 
==Interferon alfa-2a (Roferon-A)==
−
===Regimen #1, Motzer, et al. 2009===
+
===Regimen #1, Motzer, et al. 2007===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 
*[[Interferon alfa-2a (Roferon-A)]] 3 million units SC 3 times per week on week 1
 
*[[Interferon alfa-2a (Roferon-A)]] 3 million units SC 3 times per week on week 1
 
**Then if tolerated, 6 million units SC 3 times per week on week 2
 
**Then if tolerated, 6 million units SC 3 times per week on week 2
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===Regimen #2, Hudes, et al. 2007===
 
===Regimen #2, Hudes, et al. 2007===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Interferon alfa-2a (Roferon-A)]] 3 million units SC 3 times per week on week 1
 
*[[Interferon alfa-2a (Roferon-A)]] 3 million units SC 3 times per week on week 1
 
**Then if tolerated, 9 million units SC 3 times per week on week 2
 
**Then if tolerated, 9 million units SC 3 times per week on week 2
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**If higher doses cannot be tolerated, highest tolerable doses of 3, 4.5, or 6 million units can be used
 
**If higher doses cannot be tolerated, highest tolerable doses of 3, 4.5, or 6 million units can be used
  
−
===Regimen #3, Escudier, et al. 2010===
+
===Regimen #3, Escudier, et al. 2007 (AVOREN)===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
 
*[[Interferon alfa-2a (Roferon-A)]] 9 million units SC 3 times per week  
 
**Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability
 
**Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability
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===References===
 
===References===
 +
# 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 Jan 11;356(2):115-24. [http://www.nejm.org/doi/full/10.1056/NEJMoa065044 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215529 PubMed]
 
# Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa066838 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538086 PubMed]
 
# Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa066838 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538086 PubMed]
−
# Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. [http://www.ncbi.nlm.nih.gov/pubmed/18156031 PubMed]
−
# Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2144.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368553 PubMed]
+
# Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. doi: 10.1200/JCO.2008.16.9847. Epub 2008 Oct 20. [http://jco.ascopubs.org/content/26/33/5422.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18936475 PubMed]
 +
# '''Update:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed] content property of [http://hemonc.org HemOnc.org]
 +
# '''Update:''' Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2144.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20368553 PubMed]
 +
# '''Update:''' Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010 May 1;28(13):2137-43. doi: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5. [http://jco.ascopubs.org/content/28/13/2137.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20368558 PubMed]
  
 
==Pazopanib (Votrient)==
 
==Pazopanib (Votrient)==
−
===Regimen, Hutson, et al. 2010; Sternberg, et al. 2010 (VEG105192); Sternberg, et al. 2013 (VEG105192); Hainsworth, et al. 2013===
+
===Regimen, Hutson, et al. 2010; Sternberg, et al. 2010 (VEG105192); Hainsworth, et al. 2013===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 
*[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals
 
*[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals
  
Line 174: Line 327:
 
# Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14. [http://jco.ascopubs.org/content/28/3/475.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20008644 PubMed]
 
# Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14. [http://jco.ascopubs.org/content/28/3/475.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20008644 PubMed]
 
# Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. [http://jco.ascopubs.org/content/28/6/1061.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20100962 PubMed]
 
# Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. [http://jco.ascopubs.org/content/28/6/1061.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20100962 PubMed]
−
# Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. [http://www.sciencedirect.com/science/article/pii/S095980491200980X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
+
# '''Update:''' Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. [http://www.sciencedirect.com/science/article/pii/S095980491200980X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
 
# Hainsworth JD, Rubin MS, Arrowsmith ER, Khatcheressian J, Crane EJ, Franco LA. Pazopanib as Second-Line Treatment After Sunitinib or Bevacizumab in Patients With Advanced Renal Cell Carcinoma: A Sarah Cannon Oncology Research Consortium Phase II Trial. Clin Genitourin Cancer. 2013 May 9. pii: S1558-7673(13)00052-9. doi: 10.1016/j.clgc.2013.04.006. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S1558767313000529 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23665131 PubMed]
 
# Hainsworth JD, Rubin MS, Arrowsmith ER, Khatcheressian J, Crane EJ, Franco LA. Pazopanib as Second-Line Treatment After Sunitinib or Bevacizumab in Patients With Advanced Renal Cell Carcinoma: A Sarah Cannon Oncology Research Consortium Phase II Trial. Clin Genitourin Cancer. 2013 May 9. pii: S1558-7673(13)00052-9. doi: 10.1016/j.clgc.2013.04.006. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S1558767313000529 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23665131 PubMed]
 +
 +
==Placebo==
 +
 +
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 +
''No treatment. Used as a comparator arm and here for reference purposes only.''
 +
 +
===References===
 +
# Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. [http://www.nejm.org/doi/full/10.1056/NEJMoa060655 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215530 PubMed]
 +
# Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961039-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18653228 PubMed]
 +
# Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. [http://jco.ascopubs.org/content/28/6/1061.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20100962 PubMed]
 +
# '''Update:''' Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20549832 PubMed]
 +
# '''Update:''' Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. [http://www.ejcancer.info/article/S0959-8049%2810%2900637-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20656473 PubMed]
 +
# '''Update:''' Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. [http://www.sciencedirect.com/science/article/pii/S095980491200980X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23321547 PubMed]
  
 
==Regorafenib (Stivarga)==
 
==Regorafenib (Stivarga)==
 
===Regimen, Eisen, et al. 2012===
 
===Regimen, Eisen, et al. 2012===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
 
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
  
Line 188: Line 370:
 
==Sorafenib (Nexavar)==
 
==Sorafenib (Nexavar)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Sorafenib (Nexavar)]] 400 mg PO BID
 
*[[Sorafenib (Nexavar)]] 400 mg PO BID
 
**Can be decreased to [[Sorafenib (Nexavar)]] 400 mg PO once per day or [[Sorafenib (Nexavar)]] 400 mg PO every other day if needed due to toxicity
 
**Can be decreased to [[Sorafenib (Nexavar)]] 400 mg PO once per day or [[Sorafenib (Nexavar)]] 400 mg PO every other day if needed due to toxicity
  
 
===References===
 
===References===
−
# Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. [http://www.ejcancer.info/article/S0959-8049%2810%2900637-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20656473 PubMed]
+
# Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. [http://www.nejm.org/doi/full/10.1056/NEJMoa060655 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215530 PubMed]
 +
# '''Update:''' Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. [http://www.ejcancer.info/article/S0959-8049%2810%2900637-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20656473 PubMed]
 
# Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. [http://annonc.oxfordjournals.org/content/22/8/1812.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21324953 PubMed]
 
# Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. [http://annonc.oxfordjournals.org/content/22/8/1812.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21324953 PubMed]
 
# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
 
# Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961613-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22056247 PubMed]
Line 198: Line 389:
 
==Sunitinib (Sutent)==
 
==Sunitinib (Sutent)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28
 
*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28
 
**Dose may be decreased to [[Sunitinib (Sutent)]] 37.5 mg or 25 mg PO once per day depending on tolerability  
 
**Dose may be decreased to [[Sunitinib (Sutent)]] 37.5 mg or 25 mg PO once per day depending on tolerability  
Line 204: Line 403:
  
 
===References===
 
===References===
 +
# 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 Jan 11;356(2):115-24. [http://www.nejm.org/doi/full/10.1056/NEJMoa065044 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17215529 PubMed]
 
# Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. [http://jco.ascopubs.org/content/26/1/127.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18165647 PubMed]
 
# Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. [http://jco.ascopubs.org/content/26/1/127.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18165647 PubMed]
−
# Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed]
+
# '''Update:''' Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. [http://jco.ascopubs.org/content/27/22/3584.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19487381 PubMed]
 
# Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19615940 PubMed]
 
# Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970162-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19615940 PubMed]
  
 
==Temsirolimus (Torisel)==
 
==Temsirolimus (Torisel)==
 
===Regimen, Hudes, et al. 2007===
 
===Regimen, Hudes, et al. 2007===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once every week
 
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once every week
  

Revision as of 03:44, 23 July 2013

Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.

Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.


Metastatic disease

Axitinib (Inlyta)

Level of Evidence: Phase III

Regimen, Rini, et al. 2011 (AXIS) & Motzer, et al. 2013 (AXIS)

  • Axitinib (Inlyta) 5 mg PO BID x at least 2 weeks
    • Then if tolerated and BP not greater than 150/90, increased to Axitinib (Inlyta) 7 mg PO BID
      • Then if tolerated and BP not greater than 150/90, increased to Axitinib (Inlyta) 10 mg PO BID
    • Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability

References

  1. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. link to original article contains verified protocol PubMed
  2. Update: Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 Apr 15. pii: S1470-2045(13)70093-7. doi: 10.1016/S1470-2045(13)70093-7. [Epub ahead of print] link to original article contains verified protocol PubMed

Bevacizumab (Avastin)

Regimen, Bukowski, et al. 2007

Level of Evidence: Randomized Phase II, >20 per arm

  • Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes (can subsequently be reduced to 60 and 30 minute infusions as tolerated) once every 2 weeks

given for up to 104 weeks, until progression of disease, or unacceptable toxicity

References

  1. Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. Epub 2007 Sep 17. link to original article contains verified protocol PubMed

Bevacizumab & Erlotinib

Regimen, Bukowski, et al. 2007

Level of Evidence: Randomized Phase II, >20 per arm

given for up to 104 weeks, until progression of disease, or unacceptable toxicity

References

  1. Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. Epub 2007 Sep 17. link to original article contains verified protocol PubMed

Bevacizumab & Interferon alfa-2a

Regimen, Escudier, et al. 2007 (AVOREN)

Level of Evidence: Phase III

Interferon alfa-2a given for up to 52 weeks, until progression of disease, or unacceptable toxicity; bevacizumab given until progression of disease or unacceptable toxicity

References

  1. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. PubMed
  2. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. doi: 10.1200/JCO.2008.16.9847. Epub 2008 Oct 20. link to original article PubMed
  3. Update: Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. link to original article contains verified protocol PubMed
  4. Update: Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010 May 1;28(13):2137-43. doi: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5. link to original article PubMed

Erlotinib (Tarceva)

Regimen, Gordon, et al. 2009 (SWOG S0317)

Level of Evidence: Phase II

given until progression of disease or unacceptable toxicity

References

  1. Gordon MS, Hussey M, Nagle RB, Lara PN Jr, Mack PC, Dutcher J, Samlowski W, Clark JI, Quinn DI, Pan CX, Crawford D. Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol. 2009 Dec 1;27(34):5788-93. Epub 2009 Nov 2. link to original article contains verified protocol PubMed

Everolimus (Afinitor)

Regimen, Motzer, et al. 2008 (RECORD-1)

Level of Evidence: Phase III

  • Everolimus (Afinitor) 10 mg PO once per day
    • Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability

References

  1. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. link to original article contains verified protocol PubMed
  2. Update: Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. link to original article contains verified protocol PubMed

Gemcitabine & Doxorubicin

Regimen, Roubaud, et al. 2011 & Haas, et al. 2012 (ECOG 8802)

Level of Evidence: Phase II

14-day cycles, given until cumulative Doxorubicin (Adriamycin) dose of 300 to 450 mg/m2 (depending on cardiac function), progression of disease, or unacceptable toxicity

Supportive medications:

References

  1. Roubaud G, Gross-Goupil M, Wallerand H, de Clermont H, Dilhuydy MS, Ravaud A. Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma. Oncology. 2011;80(3-4):214-8. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
  2. Haas NB, Lin X, Manola J, Pins M, Liu G, McDermott D, Nanus D, Heath E, Wilding G, Dutcher J. A phase II trial of doxorubicin and gemcitabine in renal cell carcinoma with sarcomatoid features: ECOG 8802. Med Oncol. 2012 Jun;29(2):761-7. Epub 2011 Feb 6. link to original article contains verified protocol PubMed

Gemcitabine & Sunitinib

Regimen, Pandya, et al. 2011

Level of Evidence: Retrospective

21-day cycles

References

  1. Pandya SS, Mier JW, McDermott DF, Cho DC. Addition of gemcitabine at the time of sunitinib resistance in metastatic renal cell cancer. BJU Int. 2011 Oct;108(8 Pt 2):E245-9. doi: 10.1111/j.1464-410X.2011.10096.x. Epub 2011 Feb 14. link to original article contains verified protocol PubMed

High-dose (HD) IL-2

Example orders

Regimen #1, McDermott, et al. 2005

Level of Evidence: Phase III

28-day cycles x up to 3 cycles

Supportive medications:

  • Ciprofloxacin (Cipro) 250 mg PO BID on days 1 to 10, 15 to 24
  • All antihypertensive therapy discontinued at least 24 hours before each cycle
  • Acetaminophen (Tylenol) 650 mg PO every 4 hours
  • Indomethacin (Indocin) 25 mg PO every 6 hours
  • Ranitidine (Zantac) 150 mg PO or Famotidine (Pepcid) 20 mg PO every 12 hours
  • Hydroxyzine (Atarax) 25 to 50 mg PO every 6 hours or Diphenhydramine (Benadryl) 25 mg PO every (note: frequency was blank in reference) hours for pruritis
  • Meperidine (Demerol) 25 to 50 mg PO every 6 hours for chills and rigors
  • "An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed"

Regimen #2, Yang, et al. 2003

Level of Evidence: Phase III

8-week cycles x up to 2 cycles

Regimen #3, Klapper, et al. 2008

Level of Evidence: Retrospective

After this one course of treatments--defined by the paper as "two cycles"--patients with stable to improved disease would receive additional courses of treatments every 2 months (no maximum number of courses listed)

Supportive medications:

  • "Routine administration of antipyretics, anti-inflammatories, antiemetics, antidiarrheals, and H2 antagonists."

References

  1. Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article contains verified protocol PubMed
  2. McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS, Tretter CP, Urba WJ, Smith JW, Margolin KA, Mier JW, Gollob JA, Dutcher JP, Atkins MB. 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. 2005 Jan 1;23(1):133-41. link to original article contains verified protocol PubMed
  3. Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008 Jul 15;113(2):293-301. link to original article contains verified protocol PubMed

Low-dose (LD) IL-2

Regimen, Yang, et al. 2003

Level of Evidence: Phase III

8-week cycles x up to 2 cycles

References

  1. Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article contains verified protocol PubMed

Subcutaneous IL-2

Regimen, Yang, et al. 2003

Level of Evidence: Phase III

8-week cycles x up to 2 cycles

References

  1. Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003 Aug 15;21(16):3127-32. link to original article contains verified protocol PubMed

Interferon alfa-2a (Roferon-A)

Regimen #1, Motzer, et al. 2007

Level of Evidence: Phase III

  • Interferon alfa-2a (Roferon-A) 3 million units SC 3 times per week on week 1
    • Then if tolerated, 6 million units SC 3 times per week on week 2
      • Then if tolerated, 9 million units SC 3 times per week on week 3 and beyond

given until progression of disease or unacceptable toxicity

Regimen #2, Hudes, et al. 2007

Level of Evidence: Phase III

  • Interferon alfa-2a (Roferon-A) 3 million units SC 3 times per week on week 1
    • Then if tolerated, 9 million units SC 3 times per week on week 2
      • Then if tolerated, 18 million units SC 3 times per week on week 3 and beyond
    • If higher doses cannot be tolerated, highest tolerable doses of 3, 4.5, or 6 million units can be used

Regimen #3, Escudier, et al. 2007 (AVOREN)

Level of Evidence: Phase III

  • Interferon alfa-2a (Roferon-A) 9 million units SC 3 times per week
    • Dose can be reduced to 3 or 6 million units SC 3 times per week based on tolerability

Interferon alfa-2a given for up to 52 weeks, until progression of disease, or unacceptable toxicity

References

  1. 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 Jan 11;356(2):115-24. link to original article contains verified protocol PubMed
  2. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article contains verified protocol PubMed
  3. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. PubMed
  4. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008 Nov 20;26(33):5422-8. doi: 10.1200/JCO.2008.16.9847. Epub 2008 Oct 20. link to original article PubMed
  5. Update: Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. link to original article contains verified protocol PubMed content property of HemOnc.org
  6. Update: Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 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 May 1;28(13):2144-50. Epub 2010 Apr 5. link to original article contains verified protocol PubMed
  7. Update: Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010 May 1;28(13):2137-43. doi: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5. link to original article PubMed

Pazopanib (Votrient)

Regimen, Hutson, et al. 2010; Sternberg, et al. 2010 (VEG105192); Hainsworth, et al. 2013

Level of Evidence: Phase III

given until progression of disease, unacceptable toxicity, death, or withdrawal of consent

References

  1. Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14. link to original article contains verified protocol PubMed
  2. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. link to original article contains verified protocol PubMed
  3. Update: Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. link to original article contains verified protocol PubMed
  4. Hainsworth JD, Rubin MS, Arrowsmith ER, Khatcheressian J, Crane EJ, Franco LA. Pazopanib as Second-Line Treatment After Sunitinib or Bevacizumab in Patients With Advanced Renal Cell Carcinoma: A Sarah Cannon Oncology Research Consortium Phase II Trial. Clin Genitourin Cancer. 2013 May 9. pii: S1558-7673(13)00052-9. doi: 10.1016/j.clgc.2013.04.006. [Epub ahead of print] link to original article contains protocol PubMed

Placebo

Regimen

Level of Evidence: Phase III

No treatment. Used as a comparator arm and here for reference purposes only.

References

  1. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. link to original article contains verified protocol PubMed
  2. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. Epub 2008 Jul 22. link to original article contains verified protocol PubMed
  3. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. Epub 2010 Jan 25. link to original article contains verified protocol PubMed
  4. Update: Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. link to original article contains verified protocol PubMed
  5. Update: Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. link to original article contains verified protocol PubMed
  6. Update: Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. link to original article contains verified protocol PubMed

Regorafenib (Stivarga)

Regimen, Eisen, et al. 2012

Level of Evidence: Phase II

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Eisen T, Joensuu H, Nathan PD, Harper PG, Wojtukiewicz MZ, Nicholson S, Bahl A, Tomczak P, Pyrhonen S, Fife K, Bono P, Boxall J, Wagner A, Jeffers M, Lin T, Quinn DI. Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol. 2012 Oct;13(10):1055-62. doi: 10.1016/S1470-2045(12)70364-9. Epub 2012 Sep 6. link to original article contains verified protocol PubMed

Sorafenib (Nexavar)

Regimen

Level of Evidence: Phase III

References

  1. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. Erratum in: N Engl J Med. 2007 Jul 12;357(2):203. link to original article contains verified protocol PubMed
  2. Update: Hutson TE, Bellmunt J, Porta C, Szczylik C, Staehler M, Nadel A, Anderson S, Bukowski R, Eisen T, Escudier B; Sorafenib TARGET Clinical Trial Group. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. Eur J Cancer. 2010 Sep;46(13):2432-40. Epub 2010 Jul 23. link to original article contains verified protocol PubMed
  3. Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, Bokemeyer C, Bracarda S, Richel DJ, Staehler M, Strauss UP, Mersmann S, Burock K, Escudier B. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol. 2011 Aug;22(8):1812-23. Epub 2011 Feb 15. link to original article contains verified protocol PubMed
  4. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. Epub 2011 Nov 4. link to original article contains verified protocol PubMed

Sunitinib (Sutent)

Regimen

Level of Evidence: Phase III

42-day cycles, given until progression of disease or unacceptable toxicity

References

  1. 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 Jan 11;356(2):115-24. link to original article contains verified protocol PubMed
  2. Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. link to original article PubMed
  3. Update: Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. Epub 2009 Jun 1. link to original article contains verified protocol PubMed
  4. Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009 Aug;10(8):757-63. Epub 2009 Jul 15. link to original article contains verified protocol PubMed

Temsirolimus (Torisel)

Regimen, Hudes, et al. 2007

Level of Evidence: Phase III

Supportive medications:

  • Diphenhydramine (Benadryl) "or similar H1 blocker" 25 to 50 mg IV once 30 minutes prior to temsirolimus

References

  1. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. link to original article contains verified protocol PubMed
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