Renal cell carcinoma

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Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page or to a histology- or biomarker-specific page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: This page contains trials that did not specify histology or allowed patients with multiple histologies. Trials limited to a specific histology including those that required a clear-cell component are on dedicated pages:
*Histology-specific:
**Clear cell renal cell carcinoma
**Non-clear cell renal cell carcinoma
***Papillary renal cell carcinoma
***Sarcomatoid renal cell carcinoma
*Biomarker-specific:
**RCC, VHL-associated
Last updated on 2024-07-23:14 regimens on this page
22 variants on this page
=Living Interactive Systematic Reviews=
*Adjuvant treatment options in renal cell carcinoma
*Metastatic renal cell carcinoma (mRCC)
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2021: Kanesveran et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma EuroPMC
*2021: Powles et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma EuroPMC
*2024: Powles et al. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
**2019: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2016: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2014: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2012: Escudier et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Escudier & Kataja. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Escudier & Kataja. Renal cell carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
==ISRS==
*2024: Siva et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS) EuroPMC
==NCCN==
*NCCN Guidelines - Kidney Cancer
**2024: Motzer et al. NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024 EuroPMC
**2022: Motzer et al. Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. link to PMC article EuroPMC
**2017: Motzer et al. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology EuroPMC
**2015: Motzer et al. Kidney Cancer, Version 3.2015 EuroPMC
**2014: Motzer et al. Kidney cancer, version 2.2014 EuroPMC
**2011: Motzer et al. Kidney cancer. EuroPMC
**2009: Motzer et al. NCCN clinical practice guidelines in oncology: kidney cancer. EuroPMC
**2006: Motzer et al. Kidney cancer. Clinical practice guidelines in oncology. EuroPMC
**2005: Motzer et al. Kidney cancer. Clinical practice guidelines. EuroPMC
==SIOG==
*2018: Kanesvaran et al. Elderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology EuroPMC
==SEOM-SOGUG==
*2023: Méndez-Vidal et al. SEOM SOGUG clinical guideline for treatment of kidney cancer (2022) EuroPMC
==SITC==
*2019: Rini et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC) EuroPMC
=Risk Stratification Calculators=
*International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) calculator
**ref: Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK; External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8. Epub 2013 Jan 9. link to PMC article EuroPMC
*Memorial Sloan Kettering Cancer Center (MSKCC) calculator
**ref: Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002 Jan 1;20(1):289-96. link to original article EuroPMC
*Mortality and complication risk calculator for a patients with clinical T1 renal cortical mass up to 7 cm (Dr. Sarah P. Psutka)
**ref: Psutka SP et al., A clinical decision aid to support personalized treatment selection for patients with stage T1 renal masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity. Working paper. link to news article
*UCLA Integrated Staging System (UISS) for Renal Cell Carcinoma (RCC)
**ref: Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D, Gitlitz BJ, deKernion JB, Figlin RA, Belldegrun AS. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57. EuroPMC
*Leibovich prognostic model
**ref: Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, Thompson RH, Parker WP. Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery. Eur Urol. 2018 May;73(5):772-780. Epub 2018 Feb 3. EuroPMC
=Adjuvant therapy=
==Sunitinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Haas et al. 2016 (ECOG-ACRIN E2805)	2006-2010 	Phase 3 (E-esc)	1. Placebo2. Sorafenib	Did not meet primary endpoint of DFS
====Preceding treatment====
*Surgery
====Targeted therapy====
*Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycle for up to 9 cycles (1 year)
===References===
#ECOG-ACRIN E2805: Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998. link to original article link to PMC article EuroPMC NCT00326898
=Metastatic disease, first-line=
==Atezolizumab & Bevacizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Rini et al. 2019 (IMmotion151)	2015-05-20 to 2016-10-12	Phase 3 (E-esc)	Sunitinib 	Seems to have longer PFS1 (co-primary endpoint)Median PFS: 11.2 vs 7.7 mo(HR 0.74, 95% CI 0.57-0.96)
1Reported efficacy is for the PD-L1-positive subgroup, which was the predefined co-primary endpoint.
Note: patients could have clear cell or sarcomatoid histology.
====Immunotherapy====
*Atezolizumab (Tecentriq) 1200 mg IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References ===
#IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02420821
##Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article link to PMC article EuroPMC
==Everolimus monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Motzer et al. 2014 (RECORD-3)	2009-2011 	Randomized Phase 2 (E-switch-ic)	Sunitinib 	Inconclusive whether non-inferior PFS (primary endpoint)Median PFS: 7.9 vs 10.7 mo(HR 1.40, 95% CI 1.20-1.80)
====Targeted therapy====
*Everolimus (Afinitor) 10 mg PO once per day
Continued indefinitely
====Subsequent treatment====
*RECORD-3, upon progression: Second-line Sunitinib
====Dose and schedule modifications====
*Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
===References===
#RECORD-3: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00903175
==Gemcitabine & Sunitinib==
===Regimen===
Study 	Dates of enrollment	Evidence
Michaelson et al. 2015 (MGH 07-212)	2007-2013 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
====Targeted therapy====
*Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 14
21-day cycles
===References===
#MGH 07-212: Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015 Oct 1;121(19):3435-43. Epub 2015 Jun 8. link to original article EuroPMC NCT00556049
==High-dose Interleukin-2==
HD IL-2: High-Dose InterLeukin-2
===Example orders===
*Example orders for High-dose (HD) IL-2 in renal cancer
===Regimen variant #1, 1.8 MU/kg/day, intermittent===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rosenberg et al. 1994	1985-1992 	Non-randomized	 	
Fyfe et al. 1995 	Not reported 	Phase 2 (RT) 	 	
McDermott et al. 2005	1997-2000 	Phase 3 (C) 	Subcutaneous IL-2 & Interferon	Might have higher PFS36 (primary endpoint)PFS36: 10.5% vs 3.3%
====Immunotherapy====
*IL-2 - Aldesleukin (Proleukin) 600,000 units/kg IV every 8 hours for up to 14 doses per week, on days 1 to 5, 15 to 19
====Supportive therapy====
*Ciprofloxacin (Cipro) 250 mg PO twice per day 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"
28-day cycle for up to 3 cycles
===Regimen variant #2, 2.16 MU/kg/day, intermittent, goal 10.8 MU===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Yang et al. 1994	1991-1993 	Phase 3 (C)	1. LD IL-2 (IV)	Seems to have higher ORR
Yang et al. 1994	1991-1993 	Phase 3 (C)	2. LD IL-2 (SC)	Seems to have higher ORR
Note: reported efficacy is based on the 2003 update.
====Immunotherapy====
*IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses
**Then after 7 to 10 days of rest, IL-2 - Aldesleukin (Proleukin) 720,000 units/kg IV every 8 hours for up to 15 doses is given again
8-week cycle for up to 2 cycles
===Regimen variant #3, 5 MU/m2/day, CI===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Figlin et al. 1999	1994-1997 	Phase 3 (C)	IL-2 & CD8+ TILs	Did not meet primary endpoint of ORR
====Immunotherapy====
*IL-2 - Aldesleukin (Proleukin) 5,000,000 units/m2/day IV continuous infusion over 96 hours, started on days 1, 8, 15, 22 (total dose per cycle: 80 MU/m2)
8-week cycles
===References===
#Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13. link to original article EuroPMC
#Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article EuroPMC
##Update: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
#Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-96. link to original article EuroPMC
#Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, Steinberg GD, Belldegrun AS. Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2521-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Low-dose Interleukin-2==
LD IL-2: Low-Dose InterLeukin-2
===Regimen variant #1, Intravenous===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Yang et al. 1994	1991-1993 	Phase 3 (E-de-esc)	1. High-dose IL-2	Seems to have lower ORR
Yang et al. 1994	1991-1993 	Phase 3 (E-de-esc)	2. LD IL-2; SC 	Not reported
Note: efficacy is based on the 2003 update.
====Immunotherapy====
*IL-2 - Aldesleukin (Proleukin) as follows:
**Week 1: 72,000 units/kg IV every 8 hours for up to 15 doses
**Then after 7 to 10 days of rest: 72,000 units/kg IV every 8 hours for up to 15 doses is given again
8-week cycle for up to 2 cycles
===Regimen variant #2, Subcutaneous===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Yang et al. 1994	1991-1993 	Phase 3 (E-de-esc)	1. High-dose IL-2	Seems to have lower ORR
Yang et al. 1994	1991-1993 	Phase 3 (E-de-esc)	2. LD IL-2; IV 	Not reported
Note: this arm was added to the trial after the interim results were announced in 1994.
====Immunotherapy====
*IL-2 - Aldesleukin (Proleukin) as follows:
**Week 1: 250,000 units/kg SC once per day for 5 days
**Weeks 2 to 6: 125,000 units/kg SC once per day for 5 days per week
8-week cycle for up to 2 cycles
===References===
#Yang JC, Topalian SL, Parkinson D, Schwartzentruber DJ, Weber JS, Ettinghausen SE, White DE, Steinberg SM, Cole DJ, Kim HI, Levin R, Guleria A, MacFarlane MP, White RL, Einhorn JH, Seipp CA, Rosenberg SA. Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. J Clin Oncol. 1994 Aug;12(8):1572-6. link to original article EuroPMC
##Update: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Interferon alfa-2a monotherapy==
===Regimen variant #1, 5 MU 5x per week===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Sagaster et al. 1995	Not reported to 1992	Phase 3 (C)	Cimetidine, Coumarin, IFN alfa-2a	Did not meet primary endpoint of ORR
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) 5,000,000 units SC once per day on days 1 to 5 (5 times per week)
7-day cycles
===Regimen variant #2, 9 MU TIW===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gore et al. 2010 (MRC RE04/EORTC GU 30012) 	2001-2006 	Phase 3 (C) 	5-FU, Interferon alfa-2a, IL-2	Did not meet primary endpoint of OS
Hawkins et al. 2016 (Active Biotech 06762004)	2007-2010 	Phase 2/3 (C)	Naptumomab estafenatox + IFNα 	Did not meet primary endpoint of OS
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) 9,000,000 units SC 3 times per week
7-day cycle for varying durations: 78 or more cycles (Active Biotech 06762004); indefinitely (MRC RE04/EORTC GU 30012)
====Dose and schedule modifications====
*Some protocols: Dose can be reduced to 3,000,000 or 6,000,000 units SC 3 times per week based on tolerability
===Regimen variant #3, 9 MU daily, with lead-in===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Motzer et al. 2000	1994-1996 	Phase 3 (C)	IFN alfa & 13-CRA	Did not meet primary endpoint of ORR
Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) as follows:
**Cycle 1: 3,000,000 units SC once per day on days 1 to 7
**Cycle 2: 6,000,000 units SC once per day on days 1 to 7
**Cycle 3 onwards: 9,000,000 units SC once per day on days 1 to 7
7-day cycles
===Regimen variant #4, 10 MU TIW, with lead-in===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ritchie et al. 1999 (MRC RE01)	1992-1997 	Phase 3 (E-switch-ooc)	MPA 	Longer OS (primary endpoint)Median OS: 8.5 vs 6 mo(HR 0.72, 95% CI 0.55-0.94)
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) as follows:
**Cycle 1: 5,000,000 units SC once per day on days 1 & 3, then 10,000,000 units SC once on day 5
**Cycles 2 to 12: 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
7-day cycle for 12 cycles
===Regimen variant #5, 10 MU TIW===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gore et al. 2010 (MRC RE04/EORTC GU 30012)	2001-2006 	Phase 3 (C)	5-FU, Interferon alfa-2a, IL-2	Did not meet primary endpoint of OS
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) 10,000,000 units SC once per day on days 1, 3, 5 (3 times per week)
7-day cycles
===Regimen variant #6, 18 MU TIW, with lead-in===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fosså et al. 1992 	1985-1986 	Phase 3 (C)	IFN alfa-2a & Vinblastine 	Did not meet efficacy endpoints
Hudes et al. 2007 (ARCC)	2003-2005 	Phase 3 (C)	1. Interferon alfa-2a & Temsirolimus	Did not meet primary endpoint of OS
Hudes et al. 2007 (ARCC)	2003-2005 	Phase 3 (C)	2. Temsirolimus 	Shorter OS
Note: Interferon alfa-2a dose was increased only if the prior dose was tolerated.
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) as follows:
**Cycle 1: 3,000,000 units SC once per day on days 1, 3, 5
**Cycle 2: 9,000,000 units SC once per day on days 1, 3, 5
**Cycle 3 onwards: 18,000,000 units SC once per day on days 1, 3, 5
7-day cycles
====Dose and schedule modifications====
*If higher doses cannot be tolerated, highest tolerable doses of 3,000,000, 4,500,500, or 6,000,000 units can be used
=== References===
# Fosså SD, Martinelli G, Otto U, Schneider G, Wander H, Oberling F, Bauer HW, Achtnicht U, Holdener EE. Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol. 1992 Apr;3(4):301-5. link to original article EuroPMC
# Sagaster P, Micksche M, Flamm J, Ludwig H. Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Ann Oncol. 1995 Dec;6(10):999-1003. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#MRC RE01: Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M. Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug;18(16):2972-80. link to original article EuroPMC
#ARCC: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00065468
#MRC RE04/EORTC GU 30012: Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial. Lancet. 2010 Feb 20;375(9715):641-8. Epub 2010 Feb 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00053820
#Active Biotech 06762004: Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle Ö, Eisen T. A randomized phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma: final analysis with baseline biomarker subgroup and trend analysis. Clin Cancer Res. 2016 Jul 1;22(13):3172-81. Epub 2016 Feb 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00420888
==Sorafenib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Stadler et al. 2010 (ARCCS) 	2005-06 to 2006-07 	Non-randomized	 	
Retz et al. 2018 (SWITCH-II)	2012-06-14 to 2016-11-14	Phase 3 (C) 	Pazopanib 	Inconclusive whether non-inferior tPFS (primary endpoint)Median tPFS: 8.6 vs 12.9 mo(HR 1.36, 95% CI 1.11-1.68)
====Targeted therapy ====
*Sorafenib (Nexavar) 400 mg PO twice per day
Continued indefinitely
====Dose and schedule modifications====
*Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
====Subsequent treatment ====
*SWITCH-II, upon progression: Pazopanib
===References===
#ARCCS: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00111020
#SWITCH-II: Retz M, Bedke J, Bögemann M, Grimm MO, Zimmermann U, Müller L, Leiber C, Teber D, Wirth M, Bolenz C, van Alphen R, De Santis M, Beeker A, Lehmann J, Indorf M, Frank M, Bokemeyer C, Gschwend JE. SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2019 Jan;107:37-45. Epub 2018 Dec 7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT01613846
==Sunitinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Gore et al. 2009 (A618-1037) 	2005-2007 	Non-randomized 	 	
Motzer et al. 2014 (RECORD-3) 	2009-2011 	Randomized Phase 2 (E-switch-ic)	Everolimus 	Inconclusive whether non-inferior PFS (primary endpoint)Median PFS: 10.7 vs 7.9 mo(HR 0.71, 95% CI 0.56-0.83)
Eichelberg et al. 2015 (SWITCH)	2009-2011 	Phase 3 (C) 	Sorafenib 	Did not meet primary endpoint of PFS
Rini et al. 2019 (IMmotion151) 	2015-05-20 to 2016-10-12	Phase 3 (C) 	Atezolizumab & Bevacizumab	Seems to have shorter PFS1Median PFS: 7.7 vs 11.2 mo(HR 1.35, 95% CI 1.04-1.75)
1Reported efficacy for IMmotion151 is for the PD-L1-positive subgroup, which was the predefined co-primary endpoint.
====Targeted therapy====
*Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycles
====Subsequent treatment====
*SWITCH, upon progression: Second-line Sorafenib
====Dose and schedule modifications====
*Per some references, dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability
===References===
#A618-1037: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00130897
#PISCES: Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Négrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. Epub 2014 Mar 31. link to original article EuroPMC NCT01064310
#RECORD-3: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00903175
#SWITCH: Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmüller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Flörcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. Epub 2015 May 4. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00732914
#IMmotion151: Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. Epub 2019 May 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02420821
##Update: Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. link to original article link to PMC article EuroPMC
==Temsirolimus monotherapy==
=== Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hudes et al. 2007 (ARCC)	2003-2005 	Phase 3 (E-RT-switch-ooc)	1. Interferon alfa-2a 	Longer OS (primary endpoint)Median OS: 10.9 vs 7.3 mo(HR 0.73, 95% CI 0.58-0.92)
Hudes et al. 2007 (ARCC)	2003-2005 	Phase 3 (E-RT-switch-ooc)	2. Interferon alfa-2a & Temsirolimus	Not reported
====Targeted therapy====
*Temsirolimus (Torisel) 25 mg IV over 30 minutes once on day 1
====Supportive therapy====
*Diphenhydramine (Benadryl) (or similar H1 blocker) 25 to 50 mg IV once on day 1; 30 minutes prior to temsirolimus
7-day cycles
===References===
#ARCC: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00065468
=Metastatic disease, second-line=
==Cabozantinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Pal et al. 2023 (CONTACT-03)	2020-07-28 to 2021-12-27	Phase 3 (C)	Cabozantinib & Atezolizumab	Did not meet co-primary endpoints of PFS/OS
====Targeted therapy====
*Cabozantinib (Cabometyx) 60 mg PO once per day on days 1 to 28, taken at least 2 hours before or 1 hour after meals
28-day cycles
===References===
#CONTACT-03: Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. Epub 2023 Jun 5. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT04338269
==Everolimus monotherapy==
=== Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Motzer et al. 2014 (RECORD-3)	2009-2011 	Randomized Phase 2 (E-switch-ic)	Sunitinib 	Might have longer PFS-2 (secondary endpoint)Median PFS-2: 25.8 vs 21.1 mo(HR 0.77, 95% CI 0.59-1.11)
====Prior treatment criteria====
*RECORD-3: Sunitinib, with progression
====Targeted therapy====
*Everolimus (Afinitor) 10 mg PO once per day
Continued indefinitely
====Dose and schedule modifications====
*Everolimus dose can be reduced to 5 mg PO once per day or every other day if needed based on tolerability
===References===
#RECORD-3: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00903175
==Sorafenib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Stadler et al. 2010 (ARCCS) 	2005-06 to 2006-07 	Non-randomized expanded access study	 	
Beck et al. 2011 (EU-ARCCS) 	2005-2007 	Non-randomized expanded access study	 	
Hutson et al. 2013 (INTORSECT)	2007-2011 	Phase 3 (C) 	Temsirolimus	Did not meet primary endpoint of PFS2Median PFS: 3.9 vs 4.3 mo(HR 1.15, 95% CI 0.93-1.41)
1Reported efficacy for TARGET is based on the 2009 update.
2While the primary endpoint (PFS) was not met in INTORSECT, the control arm actually had longer OS compared to the experimental arm.
====Prior treatment criteria====
*INTORSECT: Sunitinib, with progression
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day
Continued indefinitely
====Dose and schedule modifications====
*Sorafenib can be decreased to 400 mg PO once per day or 400 mg PO every other day if needed due to toxicity
===References===
#ARCCS: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00111020
#EU-ARCCS: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
#INTORSECT: Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. Epub 2013 Dec 2. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT00474786
==Sunitinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Motzer et al. 2005 (RTKC-0511-014)	2003 	Phase 2 (RT) 	 	
Gore et al. 2009 (A618-1037) 	2005-2007 	Non-randomized 	 	
Motzer et al. 2014 (RECORD-3) 	2009-2011 	Randomized Phase 2 (E-switch-ic)	Everolimus	Might have shorter PFS-2 (secondary endpoint)Median PFS-2: 21.1 vs 25.8 mo(HR 1.30, 95% CI 0.90-1.70)
====Preceding treatment====
*RECORD-3: First-line Everolimus
====Targeted therapy====
*Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycles
====Dose and schedule modifications====
*Dose may be decreased to 37.5 mg or 25 mg PO once per day depending on tolerability
===References===
#RTKC-0511-014: Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006 Jan 1;24(1):16-24. Epub 2005 Dec 5. link to original article EuroPMC
#A618-1037: 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00130897
#RECORD-3: 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00903175
Category:Renal cell carcinoma regimens
Category:Disease-specific pages
Category:Genitourinary cancers