Difference between revisions of "Renal cell carcinoma"
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=Metastatic disease= | =Metastatic disease= | ||
==Axitinib (Inlyta)== | ==Axitinib (Inlyta)== | ||
| − | ===Regimen=== | + | ===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 | ||
| − | **Then if tolerated and BP not greater than 150/90, increased to 7 mg PO BID | + | **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 10 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 | + | **Dose can be reduced to 2 to 3 mg PO BID if needed based on tolerability |
===References=== | ===References=== | ||
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==Bevacizumab (Avastin)== | ==Bevacizumab (Avastin)== | ||
| − | ===Regimen=== | + | ===Regimen, Bukowski, et al. 2007=== |
| − | *[[Bevacizumab (Avastin)]] 10 mg/kg IV over 90 minutes (can subsequently be reduced to 60 and 30 minute infusions as tolerated) 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''' | '''given for up to 104 weeks, until progression of disease, or unacceptable toxicity''' | ||
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# 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] | # 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 | + | ==Bevacizumab & Interferon alfa-2a== |
| − | ===Regimen=== | + | ===Regimen, Escudier, et al. 2010 (AVOREN)=== |
| − | *[[Bevacizumab (Avastin)]] 10 mg/kg IV 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 | ||
**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 | ||
| Line 38: | Line 38: | ||
==Erlotinib (Tarceva)== | ==Erlotinib (Tarceva)== | ||
| − | ===Regimen=== | + | ===Regimen, Gordon, et al. 2009 (SWOG S0317)=== |
| − | *[[Erlotinib (Tarceva)]] 150 mg PO | + | *[[Erlotinib (Tarceva)]] 150 mg PO once per day, given 1 hour before or 2 hours after meals |
'''given until progression of disease or unacceptable toxicity''' | '''given until progression of disease or unacceptable toxicity''' | ||
| Line 47: | Line 47: | ||
==Everolimus (Afinitor)== | ==Everolimus (Afinitor)== | ||
| − | ===Regimen=== | + | ===Regimen, Motzer, et al. 2008 (RECORD-1) & Motzer, et al. 2010 (RECORD-1)=== |
| − | *[[Everolimus (Afinitor)]] 10 mg PO | + | *[[Everolimus (Afinitor)]] 10 mg PO once per day |
| − | **Dose can be reduced to 5 mg PO | + | **Dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability |
===References=== | ===References=== | ||
| Line 55: | Line 55: | ||
# 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] | # 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 | + | ==Gemcitabine & Doxorubicin== |
| − | ===Regimen=== | + | ===Regimen, Roubaud, et al. 2011 & Haas, et al. 2012 (ECOG 8802)=== |
| − | *[[Gemcitabine (Gemzar)]] 1500 mg/m2 IV over 30 minutes on day 1 | + | *[[Gemcitabine (Gemzar)]] 1500 mg/m2 IV over 30 minutes once on day 1 |
| − | *[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV push on day 1 | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV push once on day 1 |
| − | '''14-day cycles, given until cumulative Doxorubicin (Adriamycin) dose of 300 | + | '''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: | Supportive medications: | ||
| − | * | + | *One of the following: |
| − | ** | + | **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on starting on day 2 or 3, given until day 10 |
| + | **[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 | ||
===References=== | ===References=== | ||
| Line 70: | Line 71: | ||
# 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. [http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21298497 PubMed] | # 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. [http://www.springerlink.com/content/dnk52234n2567m5h/?MUD=MP link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21298497 PubMed] | ||
| − | ==Gemcitabine | + | ==Gemcitabine & Sunitinib== |
| − | ===Regimen=== | + | ===Regimen, Pandya, et al. 2011=== |
| − | *[[Gemcitabine (Gemzar)]] 750 mg/m2 IV over 90 minutes 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 on days 2 | + | *[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 2 to 15 |
'''21-day cycles''' | '''21-day cycles''' | ||
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==High-dose (HD) IL-2== | ==High-dose (HD) IL-2== | ||
| + | ===Example orders=== | ||
| + | *[[Example orders for High-dose (HD) IL-2 in renal cancer]] | ||
| + | |||
===Regimen #1, McDermott, et al. 2005=== | ===Regimen #1, McDermott, et al. 2005=== | ||
| − | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 600,000 units/kg IV every 8 hours x up to 14 doses per week, on days 1 | + | *[[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 |
'''28-day cycles x up to 3 cycles''' | '''28-day cycles x up to 3 cycles''' | ||
| − | |||
| − | |||
Supportive medications: | Supportive medications: | ||
| − | *Ciprofloxacin (Cipro) 250 mg PO BID on days 1 | + | *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 | *All antihypertensive therapy discontinued at least 24 hours before each cycle | ||
*Acetaminophen (Tylenol) 650 mg PO every 4 hours | *Acetaminophen (Tylenol) 650 mg PO every 4 hours | ||
*Indomethacin (Indocin) 25 mg PO every 6 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 | + | *Meperidine (Demerol) 25 to 50 mg PO every 6 hours for chills and rigors |
*"An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed" | *"An antidiarrheal agent, antiemetics, anxiolytics, diuretics, and vasopressors as needed" | ||
===Regimen #2, Yang, et al. 2003=== | ===Regimen #2, Yang, et al. 2003=== | ||
*[[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 | + | **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 |
'''8-week cycles x up to 2 cycles''' | '''8-week cycles x up to 2 cycles''' | ||
| Line 106: | Line 108: | ||
===Regimen #3, Klapper, et al. 2008=== | ===Regimen #3, Klapper, et al. 2008=== | ||
*[[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 | + | **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 |
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) | 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) | ||
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==Low-dose (LD) IL-2== | ==Low-dose (LD) IL-2== | ||
| − | ===Regimen=== | + | ===Regimen, Yang, et al. 2003=== |
*[[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 | + | **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 |
'''8-week cycles x up to 2 cycles''' | '''8-week cycles x up to 2 cycles''' | ||
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==Subcutaneous IL-2== | ==Subcutaneous IL-2== | ||
| − | ===Regimen=== | + | ===Regimen, Yang, et al. 2003=== |
| − | *[[Aldesleukin (Proleukin)|IL-2 - Aldesleukin (Proleukin)]] 250,000 units/kg SC 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 x 5 days per week during weeks 2 | + | **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 |
'''8-week cycles x up to 2 cycles''' | '''8-week cycles x up to 2 cycles''' | ||
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==Pazopanib (Votrient)== | ==Pazopanib (Votrient)== | ||
| − | ===Regimen=== | + | ===Regimen, Hutson, et al. 2010; Sternberg, et al. 2010 (VEG105192); Sternberg, et al. 2013 (VEG105192); Hainsworth, et al. 2013=== |
| − | *[[Pazopanib (Votrient)]] 800 mg PO | + | *[[Pazopanib (Votrient)]] 800 mg PO once per day, given 1 hour before or 2 hours after meals |
| + | |||
| + | '''given until progression of disease, unacceptable toxicity, death, or withdrawal of consent''' | ||
===References=== | ===References=== | ||
| + | # 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] | ||
| + | # 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] | ||
| + | |||
| + | ==Regorafenib (Stivarga)== | ||
| + | ===Regimen, Eisen, et al. 2012=== | ||
| + | *[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal | ||
| + | |||
| + | '''28-day cycles, given until progression of disease or unacceptable toxicity''' | ||
| + | |||
| + | ===References=== | ||
| + | # 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. [http://www.sciencedirect.com/science/article/pii/S1470204512703649 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22959186 PubMed] | ||
==Sorafenib (Nexavar)== | ==Sorafenib (Nexavar)== | ||
===Regimen=== | ===Regimen=== | ||
*[[Sorafenib (Nexavar)]] 400 mg PO BID | *[[Sorafenib (Nexavar)]] 400 mg PO BID | ||
| − | **Can be decreased to 400 mg PO | + | **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=== | ||
| Line 182: | Line 198: | ||
==Sunitinib (Sutent)== | ==Sunitinib (Sutent)== | ||
===Regimen=== | ===Regimen=== | ||
| − | *[[Sunitinib (Sutent)]] 50 mg PO on days 1 | + | *[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28 |
| − | **Dose may be decreased to 37.5 mg or 25 mg depending on tolerability | + | **Dose may be decreased to [[Sunitinib (Sutent)]] 37.5 mg or 25 mg PO once per day depending on tolerability |
'''42-day cycles, given until progression of disease or unacceptable toxicity''' | '''42-day cycles, given until progression of disease or unacceptable toxicity''' | ||
| Line 193: | Line 209: | ||
==Temsirolimus (Torisel)== | ==Temsirolimus (Torisel)== | ||
| − | ===Regimen=== | + | ===Regimen, Hudes, et al. 2007=== |
| − | *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes every week | + | *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once every week |
Supportive medications: | Supportive medications: | ||
| − | *Diphenhydramine (Benadryl) "or similar H1 blocker" 25 | + | *Diphenhydramine (Benadryl) "or similar H1 blocker" 25 to 50 mg IV once 30 minutes prior to temsirolimus |
===References=== | ===References=== | ||
# 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] | ||
Revision as of 14:42, 14 June 2013
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Metastatic disease
Axitinib (Inlyta)
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
- Then if tolerated and BP not greater than 150/90, increased to Axitinib (Inlyta) 7 mg PO BID
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. link to original article contains verified protocol 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] link to original article contains verified protocol PubMed
Bevacizumab (Avastin)
Regimen, Bukowski, et al. 2007
- 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. link to original article contains verified protocol PubMed
Bevacizumab & Interferon alfa-2a
Regimen, Escudier, et al. 2010 (AVOREN)
- Bevacizumab (Avastin) 10 mg/kg IV once every 2 weeks
- 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; bevacizumab given until progression of disease or unacceptable toxicity
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. link to original article contains verified protocol PubMed
Erlotinib (Tarceva)
Regimen, Gordon, et al. 2009 (SWOG S0317)
- Erlotinib (Tarceva) 150 mg PO once per day, given 1 hour before or 2 hours after meals
given until progression of disease or unacceptable toxicity
References
- 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) & Motzer, et al. 2010 (RECORD-1)
- 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
- 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
- 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)
- Gemcitabine (Gemzar) 1500 mg/m2 IV over 30 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV push once on day 1
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:
- One of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on starting on day 2 or 3, given until day 10
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
References
- 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
- 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
- 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
21-day cycles
References
- 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
- 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
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
- 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, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours x up to 15 doses is given again
8-week cycles x up to 2 cycles
Regimen #3, Klapper, et al. 2008
- 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, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours x up to 12 doses is given again
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
- 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
- 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
- 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
- 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, IL-2 - Aldesleukin (Proleukin) 72,000 units/kg IV every 8 hours x up to 15 doses is given again
8-week cycles x up to 2 cycles
References
- 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
- IL-2 - Aldesleukin (Proleukin) 250,000 units/kg SC once per day x 5 days on week 1
- Then IL-2 - Aldesleukin (Proleukin) 125,000 units/kg SC once per day x 5 days per week during weeks 2 to 6
8-week cycles x up to 2 cycles
References
- 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. 2009
- 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
- Then if tolerated, 6 million units SC 3 times per week on week 2
given until progression of disease or unacceptable toxicity
Regimen #2, Hudes, et al. 2007
- 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
- Then if tolerated, 9 million units SC 3 times per week on week 2
Regimen #3, Escudier, et al. 2010
- 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
- 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
- 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
- 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
Pazopanib (Votrient)
Regimen, Hutson, et al. 2010; Sternberg, et al. 2010 (VEG105192); Sternberg, et al. 2013 (VEG105192); Hainsworth, et al. 2013
- Pazopanib (Votrient) 800 mg PO once per day, given 1 hour before or 2 hours after meals
given until progression of disease, unacceptable toxicity, death, or withdrawal of consent
References
- 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
- 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
- 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
- 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
Regorafenib (Stivarga)
Regimen, Eisen, et al. 2012
- Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21, given while fasting or after a light meal
28-day cycles, given until progression of disease or unacceptable toxicity
References
- 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
- 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
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. link to original article contains verified protocol 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. link to original article contains verified protocol 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. link to original article contains verified protocol PubMed
Sunitinib (Sutent)
Regimen
- 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
42-day cycles, given until progression of disease or unacceptable toxicity
References
- 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
- 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
- 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
- Temsirolimus (Torisel) 25 mg IV over 30 minutes once every week
Supportive medications:
- Diphenhydramine (Benadryl) "or similar H1 blocker" 25 to 50 mg IV once 30 minutes prior to temsirolimus
References
- 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