Skip to main content

Advertisement

SpringerLink
Log in

Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma

  • PHASE II STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Sunitinib is associated with a robust objective response rate in patients with metastatic clear cell renal cell carcinoma (RCC). The primary objective of this phase II clinical trial was to assess the overall response rate for sunitinib in patients with papillary metastatic RCC as well as other non-clear cell histologies. A Simon 2-stage design was used to determine the number of papillary metastatic RCC patients for enrollment, and allowed for descriptive response data for other non-clear cell histologies. Twenty-three patients were enrolled, including 8 with papillary renal cell carcinoma (RCC) and the remainder with other non-clear cell histologies (unclassified in 5 patients). All patients received 50 mg of oral sunitinib in cycles of 4 weeks followed by 2 weeks of rest (4/2). The trial was stopped early because of slow accrual; no responses were observed in the 8 patients with papillary RCC. In the 22 evaluable patients, best response to sunitinib included a partial response in 1 patient with unclassified RCC, stable disease in 15, and progression in 6. The median progression-free survival was 5.5 months (95% CI, 2.5–7.1) in all 23 patients, and 5.6 months for the 8 papillary patients (95% CI, 1.4–7.1). The robust objective responses sunitinib had produced in clear cell RCC could not be demonstrated in this study comprised of patients with non-clear cell histologies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

mRCC:

Metastatic renal cell carcinoma

RCC:

Renal cell carcinoma

HLRCC:

Hereditary leiomyomatosis and renal cell cancer

CTCAE:

Common toxicity criteria for adverse events

RECIST:

Response evaluation criteria in solid tumors

References

  1. Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875

    Article  PubMed  CAS  Google Scholar 

  2. Reuter VE, Presti JC Jr (2000) Contemporary approach to the classification of renal epithelial tumors. Semin Oncol 27:124–137

    PubMed  CAS  Google Scholar 

  3. van den Berg E, van der Hout AH, Oosterhuis JW, Storkel S, Dijkhuizen T, Dam A, Zweers HM, Mensink HJ, Buys CH, de Jong B (1993) Cytogenetic analysis of epithelial renal-cell tumors: relationship with a new histopathological classification. Int J Cancer 55:223–227

    Article  PubMed  Google Scholar 

  4. Weiss LM, Gelb AB, Medeiros LJ (1995) Adult renal epithelial neoplasms. Am J Clin Pathol 103:624–635

    PubMed  CAS  Google Scholar 

  5. Kovacs G, Szucs S, De Riese W, Baumgartel H (1987) Specific chromosome aberration in human renal cell carcinoma. Int J Cancer 40:171–178

    Article  PubMed  CAS  Google Scholar 

  6. Fleming S (1993) The impact of genetics on the classification of renal carcinoma. Histopathology 22:89–92

    Article  PubMed  CAS  Google Scholar 

  7. 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 (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  PubMed  CAS  Google Scholar 

  8. 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 (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281

    Article  PubMed  CAS  Google Scholar 

  9. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456

    Article  PubMed  CAS  Google Scholar 

  10. 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 (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  PubMed  CAS  Google Scholar 

  11. Escudier B, Koralewski P, Pluzanska A, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Moore N, on behalf of the Ai (2007) A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-{alpha}2a vs placebo/interferon-{alpha}2a as first-line therapy in metastatic renal cell carcinoma. J Clin Oncol (Meeting Abstracts) 25:3

    Google Scholar 

  12. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, Atkins JN, Picus J, Czaykowski P, Dutcher J, Small EJ (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428

    Article  PubMed  CAS  Google Scholar 

  13. 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 (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590

    Article  PubMed  CAS  Google Scholar 

  14. Mai KT, Landry DC, Robertson SJ, Commons AS, Burns BF, Thijssen A, Collins J (2001) A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor. Pathol Res Pract 197:671–675

    Article  PubMed  CAS  Google Scholar 

  15. Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V (2002) Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol 20:2376–2381

    Article  PubMed  Google Scholar 

  16. Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB (2005) Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. J Immunother 28:488–495

    Article  PubMed  CAS  Google Scholar 

  17. Motzer RJ, Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163:408–417

    Article  PubMed  CAS  Google Scholar 

  18. Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B (2008) Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 26:127–131

    Article  PubMed  CAS  Google Scholar 

  19. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10

    Article  PubMed  CAS  Google Scholar 

  20. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  21. Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516–2524

    Article  PubMed  CAS  Google Scholar 

  22. Ravaud A, Oudard S, Gravis-Mescam G, Sevin E, Zanetta S, Theodore C, de Fromont M, Mahier-Ait Oukhatar C, Chene G, Escudier B (2009) First-line sunitinib in type I and II papillary renal cell carcinoma (PRCC): SUPAP, a phase II study of the French Genito-Urinary Group (GETUG) and the Group of Early Phase trials (GEP). J Clin Oncol (Meeting Abstracts) 27:5146

    Google Scholar 

  23. Plimack ER, Jonasch E, Bekele BN, Smith LA, Araujo JC, Tannir NM (2008) Sunitinib in non-clear cell renal cell carcinoma (ncc-RCC): a phase II study. J Clin Oncol (Meeting Abstracts) 26:5112

    Google Scholar 

  24. Plimack ER, Jonasch E, Bekele BN, Qiao W, Ng CS, Tannir NM (2010) Sunitinib in papillary renal cell carcinoma (pRCC): results from a single-arm phase II study. J Clin Oncol (Meeting Abstracts) 28:4604

    Google Scholar 

  25. Gordon MS, Hussey M, Nagle RB, Lara PN Jr, Mack PC, Dutcher J, Samlowski W, Clark JI, Quinn DI, Pan CX, Crawford D (2009) Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol 27:5788–5793

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by Pfizer, Inc. The authors wish to thank Carol Pearce, MSKCC Department of Medicine writer/editor, for her review of this manuscript.

Author information

Authors and Affiliations

  1. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Ana M. Molina, Darren R. Feldman, Glenn Kroog, Murielle Georges & Robert J. Motzer

  2. Department of Medical Imaging, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Michelle S. Ginsberg

  3. Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Satish K. Tickoo & Victor E. Reuter

  4. Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Xiaoyu Jia & Sujata Patil

  5. Cardiology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Michael S. Baum

  6. Department of Medicine, Weil Medical College of Cornell University, New York, NY, USA

    Ana M. Molina, Darren R. Feldman, Glenn Kroog & Robert J. Motzer

Authors
  1. Ana M. Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Darren R. Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michelle S. Ginsberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Glenn Kroog
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Satish K. Tickoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoyu Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Murielle Georges
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sujata Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael S. Baum
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Victor E. Reuter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert J. Motzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert J. Motzer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molina, A.M., Feldman, D.R., Ginsberg, M.S. et al. Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma. Invest New Drugs 30, 335–340 (2012). https://doi.org/10.1007/s10637-010-9491-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-010-9491-6

Keywords

Search

Navigation