Renal cell carcinoma - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main RCC page for current regimens.

9 regimens on this page 9 variants on this page

Metastatic disease, first-line

Interferon alfa-2a & Interleukin-2

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Negrier et al. 1998	1992-1995	Phase 3 (E-esc)	1. HD IL-2 2. Interferon alfa-2a	Superior EFS
Passalacqua et al. 2009	1998-2003	Phase 3 (C)	Maintenance IFN & IL-2	Did not meet primary endpoint of OS
Négrier et al. 2008 (LEONB-PERCY-DUO)	2000-2005	Phase 3 (C)	IFN & IL-2; IV IL-2	Did not meet primary endpoint of OS

Immunotherapy

• Interferon alfa-2a (Roferon-A)
• Aldesleukin (Proleukin)

References

1. Négrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T; Groupe Français d'Immunothérapie. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med. 1998 Apr 30;338(18):1272-8. link to original article PubMed
2. LEONB-PERCY-DUO: Négrier S, Perol D, Ravaud A, Bay JO, Oudard S, Chabaud S, Fargeot P, Delva R, Deplanque G, Gravis G, Escudier B; French Immunotherapy Group. Randomized study of intravenous versus subcutaneous interleukin-2, and IFNalpha in patients with good prognosis metastatic renal cancer. Clin Cancer Res. 2008 Sep 15;14(18):5907-12. link to original article PubMed NCT00416871
3. Passalacqua R, Buzio C, Buti S, Porta C, Labianca R, Pezzuolo D, Camisa R, Sabbatini R, Benecchi L, Messina C, Cengarle R, Vaglio A, Dalla Chiesa M, Tomasello G, Caminiti C. Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer. Cancer Immunol Immunother. 2010 Apr;59(4):553-61. Epub 2009 Sep 25. link to original article PubMed

Medroxyprogesterone monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ritchie et al. 1999 (MRC RE01)	1992-1997	Phase 3 (C)	IFN alfa-2a	Seems to have inferior OS
Negrier et al. 2007 (PERCY Quattro)	2000-2004	Phase 3 (C)	1. IFN alfa-2a 2. IFN alfa-2a & IL-2 3. IL-2	Did not meet primary endpoint of OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Hormone replacement therapy

• Medroxyprogesterone (MPA)

References

1. 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 contains protocol PubMed
2. PERCY Quattro: Negrier S, Perol D, Ravaud A, Chevreau C, Bay JO, Delva R, Sevin E, Caty A, Escudier B; French Immunotherapy Intergroup. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer. 2007 Dec 1;110(11):2468-77. link to original article PubMed NCT00416429

Vinblastine monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pyrhönen et al. 1999	1988-1994	Phase 3 (C)	Vinblastine & IFN alfa-2a	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

• Vinblastine (Velban)

References

1. Pyrhönen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T, Juusela H, Rintala E, Hietanen P, Kellokumpu-Lehtinen PL. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999 Sep;17(9):2859-67. link to original article PubMed

Metastatic disease, second-line

FC, then allo HSCT

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FC: Fludarabine & Cyclophosphamide

Regimen

Study	Evidence
Childs et al. 2000	Non-randomized, <20 pts

Chemotherapy

• Fludarabine (Fludara) 25 mg/m² IV once per day on days -5 to -1
• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -7 & -6

Immunotherapy

• Allogeneic stem cells transfused on day 0

One course

Immunotherapy

• Allogeneic stem cells

Stem cells transfused on day 0

References

1. Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. link to original article contains verified protocol PubMed

Interferon alfa-2a monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Aass et al. 2005 (EORTC 30951)	1998-2001	Phase III (C)	IFN alfa-2a & Isotretinoin	Seems to have inferior OS

Immunotherapy

• Interferon alfa-2a (Roferon-A)

References

1. EORTC 30951: Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. link to original article PubMed NCT00002737

Interferon alfa-2a & Isotretinoin

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Aass et al. 2005 (EORTC 30951)	1998-2001	Phase III (E-esc)	IFN alfa-2a	Seems to have superior OS

Immunotherapy

• Interferon alfa-2a (Roferon-A)
• Isotretinoin (Accutane)

References

1. EORTC 30951: Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. link to original article PubMed NCT00002737

Interferon alfa-2c monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
De Mulder et al. 1995 (EORTC 30885)	1988-1990	Phase III (C)	IFN alfa-2c & IFN gamma	Did not meet efficacy endpoints

Immunotherapy

• Interferon alfa-2c (Berofor)

References

1. EORTC 30885: De Mulder PH, Oosterhof G, Bouffioux C, van Oosterom AT, Vermeylen K, Sylvester R; EORTC Genitourinary Group. EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. Br J Cancer. 1995 Feb;71(2):371-5. link to original article link to PMC article PubMed

Megestrol monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ravaud et al. 2008	2002-2005	Phase III (C)	Lapatinib	Did not meet primary endpoint of TTP

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Hormone replacement therapy

• Megestrol (Megace)

References

1. Ravaud A, Hawkins R, Gardner JP, von der Maase H, Zantl N, Harper P, Rolland F, Audhuy B, Machiels JP, Pétavy F, Gore M, Schöffski P, El-Hariry I. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial. J Clin Oncol. 2008 May 10;26(14):2285-91. link to original article PubMed