World Journal of Urology

, Volume 28, Issue 3, pp 343–351 | Cite as

Management of sunitinib-related adverse events: an evidence- and expert-based consensus approach

  • Viktor Grünwald
  • Daniel Kalanovic
  • Axel S. Merseburger
Topic Paper



The advance of medical treatment in renal cell carcinoma (RCC) has fostered the development of diverse continuous oral therapies with tyrosine kinase inhibitors (TKI), among these sunitinib remains the mainstay of therapy for most of the patients. Based on its clinical activity, disease control over a period of 11 months can be expected with sunitinib treatment. Given this prolonged period of exposure to sunitinib, adverse events tend to reoccur and can possibly decrease the quality of life in our patients. Hence, development of modalities to detect, treat and cope with such adverse events has become a major focus for physicians and patients. Today, numerous publications address these questions and offer advice from experienced centers. However, these reviews summarize single or oligo-center experiences.

Methods and Results

Our approach is based (1) on an extensive review and analysis of available evidence from literature and (2) a structured consensus survey among 12 German experts in the field who treated at least 30 patients each with a TKI.


Derived from this process, this paper gives an overview on Sunitinib therapy management recommendations deducted from published evidence and consensus agreement among experts.


Sunitinib Adverse events Management Survey 


  1. 1.
    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 27:3584–3590CrossRefPubMedGoogle Scholar
  2. 2.
    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 356:115–124CrossRefPubMedGoogle Scholar
  3. 3.
    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 356:2271–2281CrossRefPubMedGoogle Scholar
  4. 4.
    Grunwald V, Heinzer H, Fiedler W (2007) Managing side effects of angiogenesis inhibitors in renal cell carcinoma. Onkologie 30:519–524CrossRefPubMedGoogle Scholar
  5. 5.
    Grunwald V, Soltau J, Ivanyi P, Rentschler J, Reuter C, Drevs J (2009) Molecular targeted therapies for solid tumors: management of side effects. Onkologie 32:129–138CrossRefPubMedGoogle Scholar
  6. 6.
    Eskens FA, Verweij J (2006) The clinical toxicity profile of vascular endothelial growth factor (vegf) and vascular endothelial growth factor receptor (vegfr) targeting angiogenesis inhibitors; a review. Eur J Cancer 42:3127–3139CrossRefPubMedGoogle Scholar
  7. 7.
    Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26:5204–5212CrossRefPubMedGoogle Scholar
  8. 8.
    Speca J, Yenser S, Creel P, George D (2006) Improving outcomes with novel therapies for patients with newly diagnosed renal cell carcinoma. Clin Genitourin Cancer 5(Suppl 1):S24–S30CrossRefPubMedGoogle Scholar
  9. 9.
    Azizi M, Chedid A, Oudard S (2008) Home blood-pressure monitoring in patients receiving sunitinib. N Engl J Med 358:95–97CrossRefPubMedGoogle Scholar
  10. 10.
    Porta C, Paglino C, Imarisio I, Bonomi L (2007) Uncovering pandora’s vase: the growing problem of new toxicities from novel anticancer agents. The case of sorafenib and sunitinib. Clin Exp Med 7:127–134CrossRefPubMedGoogle Scholar
  11. 11.
    Desai JG, Pavlakis H, McAarthur N, Davis ID GA (2007) Sunitinib malate in the treatment of renal cell carcinoma and gastrointestinal stromal tumor: Recommendations for patient management. Asia-Pacific Journal of Clinical Oncology 3:167–176Google Scholar
  12. 12.
    Bhargava P (2009) Vegf kinase inhibitors: How do they cause hypertension? Am J Physiol Regul Integr Comp Physiol 297:R1–R5PubMedGoogle Scholar
  13. 13.
    Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J, George S, Morgan JA, Harris DM, Ismail NS, Chen J-H, Schoen FJ, Van den Abbeele AD, Demetri GD, Force T, Chen MH (2007) Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:2011–2019CrossRefPubMedGoogle Scholar
  14. 14.
    Negrier S, Ravaud A (2007) Optimisation of sunitinib therapy in metastatic renal cell carcinoma: Adverse-event management. Eur J Cancer Suppl 5:12–19CrossRefGoogle Scholar
  15. 15.
    Summary of product characteristics; sutent®Google Scholar
  16. 16.
    Di Lorenzo G, Autorino R, Bruni G, Cartenì G, Ricevuto E, Tudini M, Ficorella C, Romano C, Aieta M, Giordano A, Giuliano M, Gonnella A, De Nunzio C, Rizzo M, Montesarchio V, Ewer M, De Placido M (2009) Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann Oncol 20:1535–1542CrossRefPubMedGoogle Scholar
  17. 17.
    Ivanyi P, Winkler T, Ganser A, Reuter C, Grunwald V (2008) Novel therapies in advanced renal cell carcinoma: Management of adverse events from sorafenib and sunitinib. Dtsch Arztebl Int 105:232–237PubMedGoogle Scholar
  18. 18.
    Izzedine H, Ederhy S, Goldwasser F, Soria JC, Milano G, Cohen A, Khayat D, Spano JP (2009) Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 20:807–815CrossRefPubMedGoogle Scholar
  19. 19.
    Bhojani N, Jeldres C, Patard JJ, Perrotte P, Suardi N, Hutterer G, Patenaude F, Oudard S, Karakiewicz PI (2008) Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol 53:917–930CrossRefPubMedGoogle Scholar
  20. 20.
    National comprehensive cancer network21® (nccn). Clinical practice guidelines in oncology™. Cancer-related fatigue (v.2.2007). Available at: http://www.Nccn.Org/professionals/physician_gls/pdf/fatigue.Pdf, 2007
  21. 21.
    Wood L (2006) Managing the side effects of sorafenib and sunitinib. Community Oncol 3:558–562Google Scholar
  22. 22.
    Kollmannsberger C, Soulieres D, Wong R, Scalera A, Gaspo R, Bjarnason G (2007) Sunitinib therapy for metastatic renal cell carcinoma: Recommendations for management of side effects. Can Urol Assoc J 1:S41–S54PubMedGoogle Scholar
  23. 23.
    Staehler M, Haseke N, Schoppler G, Stadler T, Heinemann G, Stief CG (2006) managing the side effects of angiogenetic inhibitors in metastatic renal cell carcinoma. Urologe A 2006;45:1333–1342; quiz 1343Google Scholar
  24. 24.
    Houk BE, Bello C, Michaelson MD, Bukowski RM, Redman BG, Hudes GR, et al. (2007) Exposure-response of sunitinib in metastatic renal cell carcinoma (mrcc): A population pharmacokinetic/pharmacodynamic (pkpd) approach. J clin Oncol ASCO Meeting Abstracts 25 Abstract: 5027Google Scholar
  25. 25.
    Botchkareva NV, Khlgatian M, Longley BJ, Botchkarev VA, Gilchrest BA (2001) Scf/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit. FASEB J 15:645–658CrossRefPubMedGoogle Scholar
  26. 26.
    Rosenbaum SE, Wu S, Newman MA, West DP, Kuzel T, Lacouture ME (2008) Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer 16:557–566CrossRefPubMedGoogle Scholar
  27. 27.
    Webster-Gandy JD, How C, Harrold K (2007) Palmar-plantar erythrodysesthesia (ppe): a literature review with commentary on experience in a cancer centre. Eur J Oncol Nurs 11:238–246CrossRefPubMedGoogle Scholar
  28. 28.
    Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, Garbe C, Hauschild A, Puzanov I, Alexandrescu DT, Anderson RT, Wood L, Dutcher JP (2008) Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist 13:1001–1011CrossRefPubMedGoogle Scholar
  29. 29.
    Esper P, Gale D, Muehlbauer P (2007) What kind of rash is it?: Deciphering the dermatologic toxicities of biologic and targeted therapies. Clin J Oncol Nurs 11:659–666CrossRefPubMedGoogle Scholar
  30. 30.
    Pfohler C (2008) US: Cutaneous reactions to molecular targeted therapies. Hautarzt 59:814–820CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Viktor Grünwald
    • 1
  • Daniel Kalanovic
    • 2
  • Axel S. Merseburger
    • 3
  1. 1.Clinic for Hematology, Hemostaseology, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  2. 2.Pfizer Pharma GmbHBerlinGermany
  3. 3.Department of Urology and Urologic OncologyHannover Medical SchoolHannoverGermany

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