Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma

Anita Schwandt, Laura S Wood, Brian Rini, Robert Dreicer, Anita Schwandt, Laura S Wood, Brian Rini, Robert Dreicer

Abstract

Advances in the understanding of the biology of renal cell carcinoma have led to recent approval of several new agents including drugs that target vascular endothelial growth factor. Sunitinib is an oral tyrosine kinase inhibitor which interferes with multiple intracellular tumorogenic pathways, and has demonstrated impressive antitumor activity in phase II and subsequently improvement in progression free survival in phase III renal cancer trials. We review the unique side effects of sunitinib therapy with emphasis on establishing effective patient education for anticipation and early management of therapy-related side effects.

Keywords: renal cell carcinoma; side effects; sunitinib; tyrosine kinase inhibitor.

Figures

Figure 1
Figure 1
Grade 3 hand-foot syndrome including acral erythema, hyperkeratotic areas, and desquamation. Considered grade 3 due to pain interfering with function.
Figure 2
Figure 2
Grade 2 hand-foot syndrome including erythema, desquamation, and skin discoloration. Considered grade 2 because mild discomfort did not interfere with function.

References

    1. McLaughlin JK, Lipworth L, Tarone RE. Epidemiologic aspects of renal cell carcinoma. Semin Oncol. 2006;33(5):527–533.
    1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.
    1. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996;335(12):865–875.
    1. Lam JS, Leppert JT, Belldegrun AS, Figlin RA. Novel approaches in the therapy of metastatic renal cell carcinoma. World J Urol. 2005;23(3):202–212.
    1. Setiawan VW, Stram DO, Nomura AM, Kolonel LN, Henderson BE. Risk factors for renal cell cancer: The multiethnic cohort. Am J Epidemiol. 2007;166(8):932–940.
    1. Karumanchi SA, Merchan J, Sukhatme VP. Renal cancer: Molecular mechanisms and newer therapeutic options. Curr Opin Nephrol Hypertens. 2002;11(1):37–42.
    1. Latif F, Tory K, Gnarra J, et al. Identification of the von hippel-lindau disease tumor suppressor gene. Science. 1993;260(5112):1317–1320.
    1. Rini BI, Small EJ. Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J Clin Oncol. 2005;23(5):1028–1043.
    1. Chow LQ, Eckhardt SG. Sunitinib: From rational design to clinical efficacy. J Clin Oncol. 2007;25(7):884–896.
    1. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9(1):327–337.
    1. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24(1):25–35.
    1. Motzer RJ, Michaelson MD, Redman BG, et al. 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. 2006;24(1):16–24.
    1. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006;295(21):2516–2524.
    1. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–124.
    1. Figlin RA, Hutson TE, Tomczak P, et al. Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC) J Clin Oncol (Meeting Abstracts) 2008;26(15 suppl):5024.
    1. Porta C, Szczylik C, Bracarda S, et al. Short- and long-term safety with sunitinib in an expanded access trial in metastatic renal cell carcinoma (mRCC) J Clin Oncol (Meeting Abstracts) 2008;26(15 suppl):5114.
    1. van der Veldt AA, Boven E, Helgason HH, et al. Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. Br J Cancer. 2008;99(2):259–265.
    1. Houk BE, Bello CL, Michaelson MD, et al. Exposure-response of sunitinib in metastatic renal cell carcinoma (mRCC): A population pharmacokinetic/pharmacodynamic (PKPD) approach. ASCO Meeting Abstracts. 2007;25(18 suppl):5027.
    1. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American college of chest physicians evidence-based clinical practice guidelines (8th edition) Chest. 2008;133(6 suppl):160S–198S.
    1. Rini BI, Tamaskar I, Shaheen P, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2007;99(1):81–83.
    1. Wolter P, Stefan C, Decallonne B, et al. The clinical implications of sunitinib-induced hypothyroidism: A prospective evaluation. Br J Cancer. 2008;99(3):448–454.
    1. Wong E, Rosen LS, Mulay M, et al. Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid. 2007;17(4):351–355.
    1. Sica DA. Angiogenesis inhibitors and hypertension: An emerging issue. J Clin Oncol. 2006;24(9):1329–1331.
    1. Dallabrida SM, Ismail N, Pravda EA, et al. Abstract 1505: Sunitinib-induced cardiotoxicity is mediated in part via direct effects on cardiac myocytes and smooth muscle cells Circulation 2007116(16 MeetingAbstracts):II 311.
    1. Kido M, Du L, Sullivan CC, et al. Hypoxia-inducible factor 1-alpha reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse. J Am Coll Cardiol. 2005;46(11):2116–2124.
    1. Parisi Q, Biondi-Zoccai GG, Abbate A, et al. Hypoxia inducible factor-1 expression mediates myocardial response to ischemia late after acute myocardial infarction. Int J Cardiol. 2005;99(2):337–339.
    1. Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370(9604):2011–2019.
    1. Khakoo AY, Kassiotis CM, Tannir N, et al. Heart failure associated with sunitinib malate: A multitargeted receptor tyrosine kinase inhibitor. Cancer. 2008;112(11):2500–2508.
    1. Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2008;26(32):5204–5212.
    1. Rosenbaum SE, Wu S, Newman MA, West DP, Kuzel T, Lacouture ME. Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer. 2008;16(6):557–566.
    1. Porta C, Paglino C, Imarisio I, Bonomi L. Uncovering pandora’s vase: The growing problem of new toxicities from novel anticancer agents. the case of sorafenib and sunitinib. Clin Exp Med. 2007;7(4):127–134.
    1. Robert C, Soria JC, Spatz A, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005;6(7):491–500.
    1. Pouessel D, Culine S. High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor. Eur Urol. 2008;53(2):376–381.
    1. Unnithan JS, Choueiri T, Garcia J, et al. Safety of VEGF-targeted tyrosine kinase inhibitors in patients (pts) with metastatic renal cell carcinoma (mRCC) and central nervous system (CNS) metastases. J Clin Oncol (Meeting Abstracts) 2007;25(18 suppl):5047.
    1. Martin G, Bellido L, Cruz JJ. Reversible posterior leukoencephalopathy syndrome induced by sunitinib. J Clin Oncol. 2007;25(23):3559.
    1. Nicholaou T, Wong R, Davis ID. Tumour lysis syndrome in a patient with renal-cell carcinoma treated with sunitinib malate. Lancet. 2007;369(9577):1923–1924.
    1. Motzer RJ, Michaelson MD, Rosenberg J, et al. Sunitinib efficacy against advanced renal cell carcinoma. J Urol. 2007;178(5):1883–1887.
    1. Rini BI, Choueiri TK, Elson P, et al. Sunitinib-induced macro-cytosis in patients with metastatic renal cell carcinoma. Cancer. 2008;113(6):1309–1314.
    1. Daly AK, King BP. Pharmacogenetics of oral anticoagulants. Pharmacogenetics. 2003;13(5):247–252.
    1. Common Terminology Criteria for Adverse Events (CTCAE version 30) National Institutes of Health 2003. Accessed on the Cancer Therapy Evaluation Program (CTEP). Available at
    1. Sunitinib (Sutent®) [package insert]. 2007. New York, NY: Pfizer Labs, Division of Pfizer Pharmaceuticals; 2007
    1. Telli ML, Witteles RM, Fisher GA, Srinivas S. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol. 2008;19(9):1613–1618.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit