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Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib

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Abstract

Background

The multikinase inhibitor sunitinib has enhanced the treatment of renal cell carcinoma and gastrointestinal stromal tumor through an improved clinical response with decreased systemic toxicities. However, sunitinib is frequently associated with dermatological adverse reactions. The physical and psychosocial impact of frequent dermatological toxicities can affect consistent antineoplastic therapy and quality of life.

Patients and methods

Dermatological adverse reaction information was compiled from Pfizer Medical Information and from abstracts from the 2007 American Society of Clinical Oncology annual meeting, Prostate Cancer Symposium, and Gastrointestinal Cancers Symposium. Published clinical trials of sunitinib in MEDLINE, Cochrane Library, Cochrane Controlled Trials Register, and EMBASE Drugs and Pharmacology databases were also included. Information was accessed on or before June 30, 2007.

Results

In the pooled analysis, all-grade hand–foot skin reaction occurred in 19% of patients (5% grades 3–4), skin discoloration in 28% (0% grades 3–4), dry skin in 16% (1% grades 3–4), skin rash in 13% (1% grades 3–4), dermatitis in 8% (2% grades 3–4), hair color changes in 10% (0% grades 3–4), alopecia in 6% (0% grades 3–4), and phototoxicity in <0.1%.

Conclusions

Dermatological reactions associated with sunitinib occur frequently. Evidence-based treatment recommendations are needed in order to maximize quality of life and optimize clinical outcome.

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References

  1. Azad A, Annunziata C, Barrett T, Chen C, Steinberg S, Kwitkowski VE, McNally D, Kotz H, Minasian L, Kohn EC (2007) Dual targeting of vascular endothelial growth factor (VEGF) with sorafenib and bevacizumab: clinical and translational results. J Clin Oncol, ASCO Annual Meeting Proceedings Part I 25(18S):3542

    Google Scholar 

  2. Bang Y, Kang Y, Kang W, Boku N, Chung H, Lanzalone S, Lechuga MJ, Sherman L, Chao R, Sobrero A (2007) Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study. J Clin Oncol 25:4603

    Article  CAS  Google Scholar 

  3. Bello CL, Sherman L, Zhou J, Verkh L, Smeraglia J, Mount J, Klamerus KJ (2006) Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects. Anticancer Drugs 17:353–358

    Article  PubMed  CAS  Google Scholar 

  4. Bhojani N, Jeldres C, Patard JJ, Perrotte P, Suardi N, Hutterer G, Patenaude F, Oudard S, Karakiewicz PI, (2007) Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol DOI 10.1016/j.euroro.2007.11.037, Nov 26 [Epub ahead of print]

  5. 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 15:645–658

    Article  PubMed  CAS  Google Scholar 

  6. Brazzelli V, Prestinari F, Barbagallo T, Rona C, Orlandi E, Passamonti F, Locatelli F, Zecca M, Villani S, Borroni G (2007) A long-term time course of colorimetric assessment of the effects of imatinib mesylate on skin pigmentation: a study of five patients. J Eur Acad Dermatol Venereol 21:384–387

    Article  PubMed  CAS  Google Scholar 

  7. Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884–896

    Article  PubMed  CAS  Google Scholar 

  8. Chu D, Lacouture ME, Fillos T, Wu S (2007) Risk of hand–foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol 47(2):176–186

    Article  CAS  Google Scholar 

  9. Cooney MM, Garcia J, Brell J, Dreicer R, Beatty K, Mekhail T, Bukowski R, Zwiebel J, Remick SC, Rini BI (2007) A phase I study of bevacizumab in combination with sunitinib in advanced solid tumors. J Clin Oncol 25:15532

    Google Scholar 

  10. Dancey J, Sausville EA (2003) Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev 2:296–313

    CAS  Google Scholar 

  11. Dasanu CA, Alexandrescu DT, Dutcher J (2007) Yellow skin discoloration associated with sorafenib use for treatment of metastatic renal cell carcinoma. South Med J 100:328–330

    PubMed  Google Scholar 

  12. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338

    Article  PubMed  CAS  Google Scholar 

  13. Donner A, Klar N (1994) Methods for comparing event rates in intervention studies when the unit of allocation is a cluster. Am J Epidemiol 140:279–289

    PubMed  CAS  Google Scholar 

  14. Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A, Vajkoczy P (2004) Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. Faseb J 18:338–340

    PubMed  CAS  Google Scholar 

  15. Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24:25–35

    Article  PubMed  CAS  Google Scholar 

  16. Feldman DR, Kondagunta GV, Ronnen EA, Fischer P, Chang R, Baum M, Ginsberg MS, Ishill N, Patil S, Motzer RJ (2007) Phase I trial of bevacizumab plus sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol 25:1

    Article  Google Scholar 

  17. Fiedler W, Serve H, Dohner H, Schwittay M, Ottmann OG, O'Farrell AM, Bello CL, Allred R, Manning WC, Cherrington JM, Louie SG, Hong W, Brega NM, Massimini G, Scigalla P, Berdel WE, Hossfeld DK (2005) A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 105:986–993

    Article  PubMed  CAS  Google Scholar 

  18. Gallagher DJ, Milowsky MI, Gerst SR, Iasonos A, Riches J, Boyle MG, Bajorin DF (2007) Phase II study of sunitinib in patients (pts) with relapsed or refractory urothelial carcinoma (UC). J Clin Oncol 25:5080

    Google Scholar 

  19. George S, Blay JY, Casali PG, Cesne AL, Morgan JA, Pokela J, Quigley MT, Tassell V, Baum CM, Demetri GD (2007) Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST. J Clin Oncol 25:10015

    Article  CAS  Google Scholar 

  20. Gore ME, Porta C, Ourdard S, Bjamason G, Castellano D, Szczylik C, Mainwaring PN, Schoffski P, Rini BI, Bulkowski RM (2007) Sunitinib in metastatic renal cell carcinoma (mRCC): preliminary assessment of toxicity in an expanded access trial with subpopulation analysis. J Clin Oncol 25:1

    Article  Google Scholar 

  21. Hagemann I, Proksch E (1996) Topical treatment by urea reduces epidermal hyperproliferation and induces differentiation in psoriasis. Acta Derm Venereol 76:353–356

    PubMed  CAS  Google Scholar 

  22. Kondagunta GV, Hudes GR, Figlin R, Wilding G, Hariharan S, Kempin SN, Fayyad R, Hoosen S, Motzer RJ (2007) Sunitinib malate (SU) plus interferon (IFN) in first line metastatic renal cell cancer (mRCC): results of a dose-finding study. J Clin Oncol 25:5101

    Google Scholar 

  23. Loden M (2003) Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders. Am J Clin Dermatol 4:771–788

    Article  PubMed  Google Scholar 

  24. Luo D, Chen H, Searles G, Jimbow K (1995) Coordinated mRNA expression of c-Kit with tyrosinase and TRP-1 in melanin pigmentation of normal and malignant human melanocytes and transient activation of tyrosinase by Kit/SCF-R. Melanoma Res 5:303–309

    Article  PubMed  CAS  Google Scholar 

  25. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini BI (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24:16–24

    Article  PubMed  CAS  Google Scholar 

  26. 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 

  27. Motzer RJ, Figlin RA, Hutson TE, Tomczak P, Bukowski RM, Rixe O, Bjarnason GA, Kim ST, Chen I, Michaelson D (2007) Sunitinib versus interferon-alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC): updated results and analysis of prognostic factors. J Clin Oncol 25:5024

    Article  Google Scholar 

  28. 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 

  29. Mrozek-Orlowski ME, Frye DK, Sanborn HM (1999) Capecitabine: nursing implications of a new oral chemotherapeutic agent. Oncol Nurs Forum 26:753–762

    PubMed  CAS  Google Scholar 

  30. Perez-Soler R, Saltz L (2005) Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 23:5235–5246

    Article  PubMed  Google Scholar 

  31. Reichardt P, Yang YK, Ruka W, Seddon B, Baum CM, Demetri GD (2007) Subpopulation analyses in a worldwide treatment-use of sunitinib (SU) in GIST patients (pts) with resistance intolerance to prior imatinib (IM) therapy. J Clin Oncol 25:10022

    Google Scholar 

  32. Rixe O, Billemont B, Izzedine H (2007) Hypertension as a predictive factor of sunitinib activity. Ann Oncol 18:1117

    Article  PubMed  CAS  Google Scholar 

  33. Robert C, Faivre S, Raymond E, Armand JP, Escudier B (2005) Subungual splinter hemorrhages: a clinical window to inhibition of vascular endothelial growth factor receptors? Ann Intern Med 143:313–314

    PubMed  Google Scholar 

  34. Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, Wechsler J, Lhomme C, Escudier B, Boige V, Armand JP, Le Chevalier T (2005) Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 6:491–500

    Article  PubMed  CAS  Google Scholar 

  35. Rock EP, Goodman V, Jiang JX, Mahjoob K, Verbois SL, Morse D, Dagher R, Justice R, Pazdur R (2007) Food and Drug Administration drug approval summary: sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. Oncologist 12:107–113

    Article  PubMed  CAS  Google Scholar 

  36. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    Article  PubMed  CAS  Google Scholar 

  37. Srinivas S, Roigas J, Gillessen S, Hamenberg U, Mulder PHD, Fountzilas G, Vogelzang N, Peschel C, Flodgren P, Escudier B (2007) Continuous daily administration of sunitinib in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC): updated results. J Clin Oncol 25:5040

    Google Scholar 

  38. Strumberg D, Clark JW, Awada A, Moore MJ, Richly H, Hendlisz A, Hirte HW, Eder JP, Lenz HJ, Schwartz B (2007) Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 12:426–437

    Article  PubMed  CAS  Google Scholar 

  39. Sweeney C, Verschraegen C, Chiorean C, Lee F, Jones S, Tye L, Bello A, Chao R, Burris H (2007) A phase I dose escalation study of sunitinib plus capecitabine in patients with advanced solid tumors. J Clin Oncol 25:3592

    Google Scholar 

  40. Tsai KY, Yang CH, Kuo TT, Hong HS, Chang JW (2006) Hand–foot syndrome and seborrheic dermatitis-like rash induced by sunitinib in a patient with advanced renal cell carcinoma. J Clin Oncol 24:5786–5788

    Article  PubMed  Google Scholar 

  41. Wood LS (2006) Nursing management: managing the side effects of sorafenib and sunitinib. Community Oncol 3:5

    Google Scholar 

  42. Zhu AX, Sahani DV, Tomaso ED, Duda D, Sindhwani V, Yoon SS, Blaszkowsky LS, Clark JW, Ryan DP, Jain RK (2007) A phase II study of sunitinib in patients with advanced hepatocellular cancer. J Clin Oncol 25:4637

    Google Scholar 

  43. Zurita AJ, Shore N, Kozloff M, Ryan CW, Beer TM, Maneval EC, Chen I, Logothetis C, (2007) Phase I study of sunitinib in combination with docetaxel and prednisone in patients (pts) with metastatic hormone refractory prostate cancer (mHPRC). In 2007 ASCO Prostate Cancer Symposium. Abstract No. 230

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Acknowledgments

We thank Alfred Rademaker for the statistical analysis. M.E.L. is supported by a Zell Scholarship from the Robert H Lurie Cancer Center.

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Authors and Affiliations

  1. Stony Brook University Cancer Center, 9447 SUNY, Room 2-160, Stony Brook, NY, 11794-9447, USA

    S. Wu

  2. Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, 676 N. St. Clair St., Suite 1600, Chicago, IL, USA

    T. Kuzel

  3. Northwestern University, Feinberg School of Medicine, 676 N. St. Clair St., Suite 1600, Chicago, IL, 60611, USA

    T. Kuzel

  4. Department of Dermatology, Northwestern University, Feinberg School of Medicine, 676 N. St. Clair St., Suite 1600, Chicago, IL, 60611, USA

    S. E. Rosenbaum, M. A. Newman, D. P. West & M. E. Lacouture

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Correspondence to M. E. Lacouture.

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Rosenbaum, S.E., Wu, S., Newman, M.A. et al. Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer 16, 557–566 (2008). https://doi.org/10.1007/s00520-008-0409-1

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  • DOI: https://doi.org/10.1007/s00520-008-0409-1

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