Skip to main content

Advertisement

Log in

Feasibility of sequential use of sunitinib and temsirolimus in advanced renal cell carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Targeted agents sunitinib and temsirolimus are effective in advanced renal cell carcinoma. Treatment algorithms for single-agent use have been proposed in order to optimize timing and type of therapy. The aim of this study was to investigate the tolerability and adverse event profile of patients who received sunitinib and temsirolimus in sequence. We performed a retrospective analysis of patients with advanced renal cell carcinoma who received temsirolimus after disease progression under sunitinib therapy. Dosages of both drugs were in accordance with the recommendations given by the respective manufacturers. Temsirolimus was provided before its official approval within a compassionate use program. Adverse event assessment followed the National Cancer Institute Common Toxicity Criteria. Thirteen patients receiving temsirolimus after progression under sunitinib were identified. Overall treatment time with targeted drugs (sunitinib/temsirolimus) was 34.8 (17–78) weeks, treatment with sunitinib was 28.6 (12–72), and with temsirolimus 6.2 (2–16) weeks, respectively, whereas mean therapy interruption time between both approaches was 4.4 (2–12) weeks. Under sunitinib, we observed 52 transient adverse events, 49 (94.2%) were of grade I/II, whereas 3 (5.8%) were of grade III. Under temsirolimus 36 adverse events, only grade I/II in nature were remarked. Sequential use of temsirolimus after progression under sunitinib seems to be feasible and results in a predictable, medically manageable side effect profile. Further evaluation is necessary to define the oncological validity of this sequencing approach.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

mTOR:

Mammalian target of rapamycin

mRCC:

Metastatic renal cell carcinoma

TKI:

Tyrosine kinase inhibitor

EMEA:

European Medicines Agency

CHMP:

Committee for medicinal products for human use

CUP:

Compassionate use program

RECIST:

Response evaluation criteria in solid tumors

MSKCC:

Memorial Sloan-Kettering Cancer Center

NCICTC:

National Cancer Institute Common Toxicity Criteria

IFN-α:

Interferon alpha

References

  1. Jemal A, et al. Cancer statistics 2007. CA Cancer J Clin. 2007;57(1):43–66. doi:10.3322/canjclin.57.1.43.

    Article  PubMed  Google Scholar 

  2. Ljungberg B, et al. European Association of Urology Guideline Group for renal cell carcinoma. Renal cell carcinoma guideline. Eur Urol. 2007;51(6):1502–10. doi:10.1016/j.eururo.2007.03.035.

    Article  PubMed  Google Scholar 

  3. Motzer RJ, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24. doi:10.1056/NEJMoa065044.

    Article  CAS  PubMed  Google Scholar 

  4. Escudier B, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34. doi:10.1056/NEJMoa060655.

    Article  CAS  PubMed  Google Scholar 

  5. Motzer RJ, et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17(8):2530–40.

    CAS  PubMed  Google Scholar 

  6. Hudes G, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271–81. doi:10.1056/NEJMoa066838.

    Article  CAS  PubMed  Google Scholar 

  7. Otto T, Eimer C, Gerullis H. Temsirolimus in renal cell carcinoma. Transplant Proc. 2008;40(10 Suppl):S36–9. doi:10.1016/j.transproceed.2008.10.006.

    Article  CAS  PubMed  Google Scholar 

  8. Gerullis H, Bergmann L, Maute L, Eimer C, Otto T. Experiences and practical conclusions concerning temsirolimus use and adverse event management in advanced renal cell carcinoma within a compassionate use program in Germany. Cancer Chemother Pharmacol. 2009;63(6):1097–102. doi:10.1007/s00280-008-0835-2.

    Article  PubMed  Google Scholar 

  9. Torisel [Package Insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc.; 2007.

  10. de Reijke TM, Bellmunt J, van Poppel H, Marreaud S, Aapro M. EORTC-GU group expert opinion on metastatic renal cell cancer. Eur J Cancer. 2009;45(5):765–73. doi:10.1016/j.ejca.2008.12.010.

    Article  PubMed  Google Scholar 

  11. Rini BI et al. CALGB 90206. A Phase III trial of bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in metastatic renal cell carcinoma. ASCO Genitourinary Cancers Symposium 2008; Abstract 5033.

  12. Motzer RJ, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372(9637):449–56. doi:10.1016/S0140-6736(08)61039-9.

    Article  CAS  PubMed  Google Scholar 

  13. Escudier B, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103–11. doi:10.1016/S0140-6736(07)61904-7.

    Article  PubMed  Google Scholar 

  14. Bellmunt J, Guix M. The medical management of metastatic renal cell carcinoma: integrating new guidelines and recommendations. BJU Int. 2009;103(5):572–7. doi:10.1111/j.1464-410X.2008.08336.x.

    Article  CAS  PubMed  Google Scholar 

  15. Eichelberg C, et al. Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: a retrospective outcome analysis. Eur Urol. 2008;54(6):1373–8. doi:10.1016/j.eururo.2008.07.051.

    Article  CAS  PubMed  Google Scholar 

  16. Bhojani N, et al. Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol. 2008;53(5):917–30. doi:10.1016/j.eururo.2007.11.037.

    Article  CAS  PubMed  Google Scholar 

  17. Tamaskar I, et al. Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J Urol. 2008;179(1):81–6. doi:10.1016/j.juro.2007.08.127.

    Article  CAS  PubMed  Google Scholar 

  18. Patel PH, Senico PL, Curiel RE, Motzer RJ. Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2009;7(1):24–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Holger Gerullis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerullis, H., Bergmann, L., Maute, L. et al. Feasibility of sequential use of sunitinib and temsirolimus in advanced renal cell carcinoma. Med Oncol 27, 373–378 (2010). https://doi.org/10.1007/s12032-009-9220-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-009-9220-1

Keywords

Navigation