Advertisement

World Journal of Urology

, Volume 29, Issue 6, pp 807–813 | Cite as

Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib

  • L. M. Riesenbeck
  • S. Bierer
  • I. Hoffmeister
  • T. Köpke
  • P. Papavassilis
  • L. Hertle
  • B. Thielen
  • E. HerrmannEmail author
Original Article

Abstract

Purpose

To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su).

Patients and methods

Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodothyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH.

Results

Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analysis, the ECOG status (P < 0.0001) as well as MSKCC criteria (P = 0.003) and response to therapy (P < 0.0001) were associated with progression-free survival (PFS). Twenty-one of 66 (31.8%) evaluable patients developed hypothyroidism during treatment. Of those patients, 8/21 (38.1%) were treated with So and 13/21 (61.9%) with Su. Response rate in this subgroup was 49.2%. Hypothyroidism was associated with a longer PFS (16.0 ± 0.8 months vs. 6.0 ±0.8 months, P = 0.032). Most patients [16/21 (76.2%)] developed abnormal TSH values during the first 4 weeks of treatment. Hormone replacement with l-thyroxine did not have an influence on survival. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, P = 0.018) and hypothyroidism (P = 0.01) were independent prognostic parameters.

Conclusions

The development of hypothyroidism during treatment might be useful as a predictor of PFS for mRCC patients undergoing treatment with targeted agents.

Keywords

Sorafenib Sunitinib Renal cell carcinoma Hypothyroidism Progression-free survival 

Notes

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781PubMedCrossRefGoogle Scholar
  2. 2.
    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) Target study group sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134PubMedCrossRefGoogle Scholar
  3. 3.
    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 356:115–124PubMedCrossRefGoogle Scholar
  4. 4.
    Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P, Bukowski R (2005) Validation and extension of the memorial sloan-kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841PubMedCrossRefGoogle Scholar
  5. 5.
    Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC (2010) European association of urology guideline group eau guidelines on renal cell carcinoma: the 2010 update. Eur Urol 58:398–406PubMedCrossRefGoogle Scholar
  6. 6.
    Motzer RJ, Agarwal N, Beard C, Bolger GB, Boston B, Carducci MA, Choueiri TK, Figlin RA, Fishman M, Hancock SL, Hudes GR, Jonasch E, Kessinger A, Kuzel TM, Lange PH, Levine EG, Margolin KA, Michaelson MD, Olencki T, Pili R, Redman BG, Robertson CN, Schwartz LH, Sheinfeld J, Wang J (2009) NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Canc Netw 7:618–630PubMedGoogle Scholar
  7. 7.
    Sternberg CN, Davis ID, Mardiak J, SZczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068PubMedCrossRefGoogle Scholar
  8. 8.
    Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296PubMedCrossRefGoogle Scholar
  9. 9.
    Wong E, Rosen LS, Mulay M, Vanvugt A, Dinolfo M, Tomoda C, Sugawara M, Hershman JM (2007) Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid 17:351–355PubMedCrossRefGoogle Scholar
  10. 10.
    Mannavola D, Coco P, Vannucchi G, Bertuelli R, Carletto M, Casali PG, Beck-Peccoz P, Fugazzola L (2007) A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab 92:3531–3534PubMedCrossRefGoogle Scholar
  11. 11.
    Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, Morgan JA, Dychter SS, Larsen PR, Demetri GD, Alexander EK (2006) Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 145:660–664PubMedGoogle Scholar
  12. 12.
    Torino F, Corsello SM, Longo R, Barnabai A, Gasparini G (2009) Is hypothyroidism a clinically relevant toxicity of tyrosine kinase inhibitors? Thyroid 19:539–540PubMedCrossRefGoogle Scholar
  13. 13.
    Surks MI, Hollowell JG (2007) Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab 92:4575–4582PubMedCrossRefGoogle Scholar
  14. 14.
    Wolter P, Stefan C, Decallonne B, Dumez H, Fieuws S, Wildiers H, Clement P, Debaere D, Van Oosterom A, Schöffski P (2008) Evaluation of thyroid dysfunction as a candidate surrogate marker for efficacy of sunitinib in patients (pts) with advanced renal cell cancer(RCC). J Clin Oncol suppl 26:abstract 5126Google Scholar
  15. 15.
    Wolter P, Stefan C, Decallonne B, Dumez H, Bex M, Carmeliet P, Schöffski P (2008) The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation. Br J Cancer 99:448–454PubMedCrossRefGoogle Scholar
  16. 16.
    Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, Clodi M, Kramer G, Zielinski CC (2010) Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer (Epub ahead of print)Google Scholar
  17. 17.
    Patel PH, Chadalavada RS, Ishill NM, Patil S, Reuter VE, Motzer RJ, Chaganti RS (2008) Hypoxia-inducible factor (HIF)1a and 2a levels in cell linies and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol suppl 26:abstract 5008Google Scholar
  18. 18.
    Hutson TE, Davis ID, Machiels JH, de Souza PL, Baker K, Bordogna W, Westlund R, Crofts T, Pandite L, Figlin RA (2008) Biomarker analysis and final efficacy results of a phase II renal cell carcinoma trial with pazopanib(GW786034). J Clin Oncol suppl 26:abstract 5046Google Scholar
  19. 19.
    Kontovinis LF, Papazisis KT, Touplikioti P, Andreadis C, Mouratidou D, Kortsaris AH (2009) Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers. BMC Cancer 9:82PubMedCrossRefGoogle Scholar
  20. 20.
    Han KS, Jung DC, Choi HJ, Jeong MS, Cho KS, Joung JY, Seo HK, Lee KH, Chung J (2010) Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy. Cancer 116:2332–2342PubMedGoogle Scholar
  21. 21.
    Rini BI, Schiller JH, Fruehauf JP, Cohen EE, Tarazi JC, Rosbrook B, Ricart AD, Olszanski AJ, Kim S, Spano J (2008) Association of diastolic blood pressure (dBP) >90 mmHg with overall survival (OS) in patients treated with axitinib (AG- 013736). J Clin Oncol suppl 26:abstract 3543Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • L. M. Riesenbeck
    • 1
  • S. Bierer
    • 1
  • I. Hoffmeister
    • 1
  • T. Köpke
    • 1
  • P. Papavassilis
    • 1
  • L. Hertle
    • 1
  • B. Thielen
    • 1
  • E. Herrmann
    • 1
    Email author
  1. 1.Department of UrologyUniversity of MünsterMünsterGermany

Personalised recommendations