Skip to main content

Advertisement

SpringerLink
Log in

Therapeutic effects and associated adverse events of first-line treatments of advanced renal cell carcinoma (RCC): a meta-analysis

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

To compare the therapeutic effects and adverse events (AE) of current first-line treatments of advanced RCC, including sorafenib, sunitinib, temsirolimus, and the combination of bevacizumab and IFN-α.

Methods

We performed a meta-analysis of randomized controlled trials of the effectiveness of the five treatments among patients with advanced RCC. The data of progressive disease, objective response rate (ORR), disease control rate (DCR), grade 3/4 AE, progression-free survival (PFS), and overall survival (OS) were extracted to assess therapeutic effects, toxicity, and prognosis, respectively.

Results

Two studies that assessed the combination of bevacizumab with IFN α (n = 1381), one sunitinib (n = 750), one sorafenib (n = 189) and one temsirolimus (n = 416) were included. Sorafenib, sunitinib, temsirolimus (R = 0.35, 95 % confidence interval [CI] 0.26–0.48, P < 0.01), and the combination of bevacizumab with IFN (R = 0.64, 95 % CI 0.42–0.99, P = 0.04) were more effective in controlling tumor progression than IFN. Sorafenib, sunitinib, and temsirolimus do not own advantage in ORR compared with IFN (R = 2.06, 95 % CI 0.53–7.95, P = 0.30), but combination of bevacizumab with IFN showed better results in ORR than IFN (R = 2.56, 95 % CI 1.91–3.42, P < 0.01). Sorafenib, sunitinib, temsirolimus (R = 2.90, 95 % CI 2.23–3.78, P < 0.01), and combination of bevacizumab with IFN (R = 2.14, 95 % CI 1.65–2.78, P < 0.01) were more effective than IFN in DCR. Sorafenib, sunitinib, and temsirolimus had similar rate of grade 3/4 AE as IFN (R = 1.21, 95 % CI 0.96–1.51, P = 0.10). Combined use of bevacizumab and IFN is associated with higher frequency of the AE (R = 2.09, 95 % CI 1.66–2.63, P < 0.01). Sorafenib and sunitinib had similar median PFS (R = 0.67, 95 % CI 0.42–1.08, P = 0.10); temsirolimus had longer median OS (R = 0.82, 95 % CI 0.67–1.00, P = 0.049) as IFN. Combined use of bevacizumab and IFN had longer median PFS (R = 0.68, 95 % CI 0.60–0.76, P < 0.01) and OS (R = 0.86, 95 % CI 0.76–0.97, P = 0.01) than IFN.

Conclusion

Sorafenib, sunitinib, temsirolimus, and the combination of bevacizumab with IFN are more effective in stabilizing disease. Combined use of bevacizumab and IFN is better than sorafenib, sunitinib, and temsirolimus in ORR, PFS, and OS, but associated with higher level of AE.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Decastro GJ, McKiernan JM (2008) Epidemiology, clinical staging, and presentation of renal cell carcinoma. Urol Clin N Am 35:581–592

    Article  Google Scholar 

  2. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  3. Garcia JA, Cowey CL, Godley PA (2009) Renal cell carcinoma. Curr Opin Oncol 21:266–271

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. van Spronsen DJ, de Weijer KJ, Mulders PF, De Mulder PH (2005) Novel treatment strategies in clear-cell metastatic renal cell carcinoma. Anticancer Drugs 16:709–717

    Article  PubMed  Google Scholar 

  6. Van Veldhuizen PJ, Hussey M, Lara PN Jr, Mack PC, Gandour-Edwards R, Clark JI et al (2009) A phase II study of gemcitabine and capecitabine in patients with advanced renal cell cancer: southwest oncology group study S0312. Am J Clin Oncol 32:453–459

    Article  PubMed Central  PubMed  Google Scholar 

  7. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  CAS  PubMed  Google Scholar 

  8. Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ et al (2007) Sunitinib efficacy against advanced renal cell carcinoma. J Urol 178:1883–1887

    Article  CAS  PubMed  Google Scholar 

  9. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111

    Article  PubMed  Google Scholar 

  10. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281

    Article  CAS  PubMed  Google Scholar 

  11. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456

    Article  CAS  PubMed  Google Scholar 

  12. Kim HL, Belldegrun AS, Freitas DG, Bui MH, Han KR, Dorey FJ et al (2003) Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis. J Urol 170:1742–1746

    Article  PubMed  Google Scholar 

  13. Higgins JPT, Green S (2013) Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration

  14. Higgins JPT, Green S, Cochrane Collaboration (2008) Cochrane handbook for systematic reviews of interventions, vol 21. Wiley-Blackwell, Chichester, p 649

    Book  Google Scholar 

  15. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed Central  PubMed  Google Scholar 

  16. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S et al (2010) 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 28:2144–2150

    Article  CAS  PubMed  Google Scholar 

  17. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L et al (2010) 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 28:2137–2143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S et al (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 Central  CAS  PubMed  Google Scholar 

  19. Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F et al (2009) Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1280–1289

    Article  CAS  PubMed  Google Scholar 

  20. Hutson TE (2011) Targeted therapies for the treatment of metastatic renal cell carcinoma: clinical evidence. Oncologist 16(Suppl 2):14–22

    Article  PubMed Central  PubMed  Google Scholar 

  21. Négrier S, Gravis G, Pérol D, Chevreau C, Delva R, Bay JO et al (2011) Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol 12:673–680

    Article  PubMed  Google Scholar 

  22. Gollob JA, Rathmell WK, Richmond TM, Marino CB, Miller EK, Grigson G et al (2007) Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol 25:3288–3295

    Article  CAS  PubMed  Google Scholar 

  23. Feldman DR, Baum MS, Ginsberg MS, Hassoun H, Flombaum CD, Velasco S et al (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1432–1439

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Jonasch E, Corn P, Pagliaro LC, Warneke CL, Johnson MM, Tamboli P et al (2010) Upfront, randomized, phase 2 trial of sorafenib versus sorafenib and low-dose interferon alfa in patients with advanced renal cell carcinoma: clinical and biomarker analysis. Cancer 116:57–65

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding for this study was provided by the Technology Development Program of Science & Technology Department of Henan (No. 122102310013). The authors also thank Shijie Zhou and Yi He (Sichuan University, Chengdu, China), who assisted with the preparation and proof reading of data and the manuscript.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of No. 1 Urology, Xinxiang Central Hospital, No. 56, Jinsui Road, Xinxiang, 453000, Henan, China

    Lei Wang, Xinli Wang & Qingdong Qiao

  2. Department of Urology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China

    Lei Wang

  3. Department of No. 2 Urology, Xinxiang Central Hospital, Xinxiang, Henan, China

    Ling Ma

  4. Department of Inspection, Xinxiang Central Hospital, Xinxiang, Henan, China

    Bing Li & Shan Guo

Authors
  1. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qingdong Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingdong Qiao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Ma, L., Wang, X. et al. Therapeutic effects and associated adverse events of first-line treatments of advanced renal cell carcinoma (RCC): a meta-analysis. Int Urol Nephrol 47, 617–624 (2015). https://doi.org/10.1007/s11255-015-0932-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-015-0932-1

Keywords

Search

Navigation