Difference between revisions of "Renal cell carcinoma"
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Revision as of 00:23, 4 August 2016
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14 regimens on this page
22 variants on this page
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Metastatic disease
Axitinib (Inlyta)
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Pt Population |
Rini et al. 2011 (AXIS) | Phase III | 19% (95% CI 15 - 24) | Sorafenib | 9% (95% CI 7 - 13) | Treatment exposed (sunitinib, cytokines) |
Hutson et al. 2013 | Phase III | 32% (95% CI NR) | Sorafenib | 15% (95% CI NR) | Treatment naive |
- 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
- 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 May;14(6):552-62. Epub 2013 Apr 15. link to original article contains verified protocol PubMed
- Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. link to original article PubMed
Bevacizumab (Avastin)
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Pt Population |
Bukowski et al. 2007 | Randomized Phase II | 13% (95% CI NR) | Bevacizumab & Erlotinib | 14% (95% CI NR) | Treatment naive |
- Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes once every 2 weeks
- Can subsequently be reduced to 60 and 30 minute infusions as tolerated
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 & Erlotinib
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Regimen
Study | Evidence | Comparator |
Bukowski et al. 2007 | Randomized Phase II | Bevacizumab |
- Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes once every 2 weeks
- Can subsequently be reduced to 60 and 30 minute infusions as tolerated
- Erlotinib (Tarceva) 150 mg PO once per day
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
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Regimen
Study | Evidence | Comparator | |
Escudier et al. 2007 (AVOREN) | Phase III | Interferon alfa-2a | |
Rini et al. 2008 (CALGB 90206) | Phase III | Interferon alfa-2a |
- 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, 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. link to original article 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. link to original article contains verified protocol 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. Epub 2008 Oct 20. link to original article 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. Epub 2010 Apr 5. link to original article PubMed
Cabozantinib (Cabometyx)
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Pt Population | Efficacy |
Choueiri et al. 2015 (METEOR) | Phase III | 21% (95% CI 16 - 28) | Everolimus | 5% (95% CI 2- 9) | Progressed after VEGFR TKI tx | Improved PFS |
- Cabozantinib (Cabometyx) 60 mg PO once per day
- At least 2 hours before or 1 hour after meals according to the Cabozantinib (Cabometyx) package insert
Used as long as clinical benefit was perceived or unacceptable toxicity
References
- Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. link to original article contains verified protocol PubMed
- Update: ASCO 2016 Abstract 4506
Erlotinib (Tarceva)
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Regimen
Study | Evidence | ORR |
Gordon et al. 2009 (SWOG S0317) | Phase II | 11% (95% CI 3 - 24) |
- 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)
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Regimen
Study | Evidence | Comparator |
Motzer et al. 2008 (RECORD-1) | Phase III | Placebo |
Motzer et al. 2014 (RECORD-3) | Randomized Phase II | Sunitinib |
Motzer et al. 2015 (CheckMate 025) | Phase III | Nivolumab |
Choueiri et al. 2015 (METEOR) | Phase III | Cabozantinib |
Motzer et al. 2015 | Randomized Phase II | Everolimus & Lenvatinib Lenvatinib |
- 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
Given until progression of disease or unacceptable toxicity.
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
- 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
- Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article PubMed
- Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Sep 25. link to original article contains verified protocol PubMed
- Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. link to original article contains verified protocol PubMed
- Update: ASCO 2016 Abstract 4506
- Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. link to original article contains verified protocol PubMed
- Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed
Everolimus & Lenvatinib
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Regimen
Study | Evidence | Comparator |
Motzer et al. 2015 | Randomized Phase II | Everolimus Lenvatinib |
- Everolimus (Afinitor) 5 mg PO once per day
- Lenvatinib (Lenvima) 18 mg PO once per day
Continued until progression or unacceptable toxicity
References
- Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. link to original article contains verified protocol PubMed
- Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed
Gemcitabine & Doxorubicin
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Regimen, Roubaud et al. 2011 & Haas et al. 2012 (ECOG 8802)
Level of Evidence: Phase II
- 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
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Regimen #1, Michaelson et al. 2013
Level of Evidence: Phase II
Patients in Michaelson et al. 2013 had disease with sarcomatoid features.
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 14
21-day cycles
Regimen #2, Pandya et al. 2011
Level of Evidence: Retrospective
- 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
- Abstract: M Dror Michaelson, David F. McDermott, Michael B. Atkins, Daniel C. Cho, Kara M. Olivier, Abraham B. Schwarzberg, Toni K. Choueiri. Combination of antiangiogenic therapy and cytotoxic chemotherapy for sarcomatoid renal cell carcinoma. 2013 ASCO Annual Meeting abstract 4512. link to abstract
High-dose (HD) IL-2
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Example orders
Regimen #1
Study | Evidence | Comparator |
McDermott et al. 2005 | Phase III | Subcutaneous IL-2 & Interferon |
- 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 cycle 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
Study | Evidence | Comparator |
Yang et al. 2003 | Phase III | Intravenous low-dose IL-2 Subcutaneous low-dose IL-2 |
- 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 cycle x up to 2 cycles
Regimen #3, Klapper et al. 2008
Level of Evidence: Retrospective
- 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
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Regimen #1, Intravenous
Study | Evidence | Comparator |
Yang et al. 2003 | Phase III | High-dose IL-2 Subcutaneous low-dose IL-2 |
- 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 cycle x up to 2 cycles
Regimen #2, Subcutaneous
Study | Evidence | Comparator |
Yang et al. 2003 | Phase III | High-dose IL-2 Intravenous low-dose IL-2 |
- 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 cycle 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)
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Regimen #1
Study | Evidence | Comparator |
Motzer et al. 2007 | Phase III | Sunitinib |
- Interferon alfa-2a (Roferon-A) as follows:
- Week 1: 3 million units SC 3 times per week
- Week 2 (if prior dose tolerated): 6 million units SC 3 times per week
- Week 3 onwards (if prior dose tolerated): 9 million units SC 3 times per week
Given until progression of disease or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator |
Hudes et al. 2007 | Phase III | Interferon alfa-2a & Temsirolimus Temsirolimus |
- Interferon alfa-2a (Roferon-A) as follows:
- Week 1: 3 million units SC 3 times per week
- Week 2 (if prior dose tolerated): 9 million units SC 3 times per week
- Week 3 onwards (if prior dose tolerated): 18 million units SC 3 times per week
- If higher doses cannot be tolerated, highest tolerable doses of 3, 4.5, or 6 million units can be used
Regimen #3
Study | Evidence | Comparator | |
Escudier et al. 2007 (AVOREN) | Phase III | Bevacizumab & Interferon alfa-2a | |
Rini et al. 2008 (CALGB 90206) | Phase III | Bevacizumab & Interferon alfa-2a | |
Escudier et al. 2009 | Randomized Phase II | Sorafenib |
- 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
- 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
- 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
- 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
- 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. link to original article 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. link to original article contains verified protocol 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. Epub 2008 Oct 20. link to original article 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. Epub 2010 Apr 5. link to original article PubMed
- Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ, Cella D, Shah S, Bukowski RM. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Mar 10;27(8):1280-9. Epub 2009 Jan 26. Erratum in: J Clin Oncol. 2009 May 1; 27(13):2305. link to original article PubMed
Lenvatinib (Lenvima)
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Regimen
Study | Evidence | Comparator |
Motzer et al. 2015 | Randomized Phase II | Everolimus Everolimus & Lenvatinib |
The 5/13/2016 FDA approved use of Lenvatinib (Lenvima) is in combination with Everolimus (Afinitor). In Motzer et al. 2015, "single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone. Everolimus & levatinib had a non-statistically signficant improved PFS compared to single-agent levatinib.
- Lenvatinib (Lenvima) 24 mg PO once per day
Continued until progression or unacceptable toxicity
References
- Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-82. Epub 2015 Oct 22. link to original article contains verified protocol PubMed
- Update: Motzer RJ, Hutson TE, Ren M3, Dutcus C3, Larkin J. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4-5. link to original article PubMed
Nivolumab (Opdivo)
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Pt Population |
Motzer et al. 2015 (CheckMate 025) | Phase III | 25% (95% CI n/a) | Everolimus | 5% (95% CI n/a) | Mixed pop; 72% had anti-angiogenic therapy |
- Nivolumab (Opdivo) 3 mg/kg IV over 60 minutes on day 1
14-day cycles
References
- Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Sep 25. link to original article contains verified protocol PubMed
Pazopanib (Votrient)
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Regimen
Study | Evidence | Comparator | |
Hutson et al. 2010 | Phase II | ||
Sternberg et al. 2010 (VEG105192) | Phase III | Placebo | |
Hainsworth et al. 2013 | Phase II | ||
Motzer et al. 2013 | Phase III | Sunitinib |
- Pazopanib (Votrient) 800 mg PO once per day, given 1 hour before or 2 hours after meals
- Dose may be decreased to 600 mg or 400 mg PO once per day depending on tolerability
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. 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
- 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. 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 Sep;11(3):270-5. Epub 2013 May 9. link to original article contains protocol PubMed
- Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. link to original article contains verified protocol PubMed
- Update: Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. link to letter PubMed
Placebo
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Regimen
Study | Evidence | Comparator | |
Escudier et al. 2007 (TARGET) | Phase III | Sorafenib | |
Motzer et al. 2008 (RECORD-1) | Phase III | Everolimus | |
Sternberg et al. 2010 (VEG105192) | Phase III | Pazopanib |
No active antineoplastic 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. link to original article contains verified protocol 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. 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, 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
- 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
- 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
- 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. Epub 2013 Jan 12. link to original article contains verified protocol PubMed
Regorafenib (Stivarga)
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Regimen
Study | Evidence |
Eisen et al. 2012 | Phase II |
- 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. Epub 2012 Sep 6. link to original article contains verified protocol PubMed
Sorafenib (Nexavar)
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Regimen
Study | Evidence | Comparator | |
Escudier et al. 2007 (TARGET) | Phase III | Placebo | |
Escudier et al. 2009 | Randomized Phase II | Interferon alfa-2a | |
Stadler et al. 2010 (ARCCS) | Non-randomized | ||
Beck et al. 2011 (EU-ARCCS) | Non-randomized | ||
Rini et al. 2011 (AXIS) | Phase III | Axitinib | |
Hutson et al. 2013 | Phase III | Axitinib |
- Sorafenib (Nexavar) 400 mg PO BID
- Can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
Continued until progression or intolerance
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. link to original article contains verified protocol 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. link to original article contains verified protocol PubMed
- Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ, Cella D, Shah S, Bukowski RM. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Mar 10;27(8):1280-9. Epub 2009 Jan 26. Erratum in: J Clin Oncol. 2009 May 1; 27(13):2305. link to original article PubMed
- Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J, Kindwall-Keller TL, Ernstoff MS, Drabkin HA, Curti BD, Chu L, Ryan CW, Hotte SJ, Xia C, Cupit L, Bukowski RM; ARCCS Study Investigators. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-80. link to original article 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
- 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 May;14(6):552-62. Epub 2013 Apr 15. link to original article contains verified protocol PubMed
- Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, Rosbrook B, Chen C, Kim S, Vogelzang NJ. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1287-94. Epub 2013 Oct 25. link to original article PubMed
Sunitinib (Sutent)
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Regimen
Study | Evidence | Comparator | |
Motzer et al. 2007 | Phase III | Interferon alfa-2a | |
Choueiri et al. 2008 | Non-randomized | ||
Gore et al. 2009 | Non-randomized | ||
Motzer et al. 2013 | Phase III | Pazopanib | |
Motzer et al. 2014 (RECORD-3) | Randomized Phase II | Everolimus |
- 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
- 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
- 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
- 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
- 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
- Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. Epub 2014 Jul 21. link to original article PubMed
- Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. link to original article contains verified protocol PubMed
- Update: Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014 May 1;370(18):1769-70. doi: 10.1056/NEJMc1400731. link to letter PubMed
Temsirolimus (Torisel)
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Regimen
Study | Evidence | Comparator |
Hudes et al. 2007 | Phase III | Interferon alfa-2a Interferon alfa-2a & Temsirolimus |
- 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