Browse > Article
http://dx.doi.org/10.3904/kjim.2014.29.1.40

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea  

Baek, Seon Ha (Department of Internal Medicine, Seoul National University Hospital)
Kim, Hyunsuk (Department of Internal Medicine, Seoul National University Hospital)
Lee, Jeonghwan (Department of Internal Medicine, Seoul National University Hospital)
Kim, Dong Ki (Department of Internal Medicine, Seoul National University Hospital)
Oh, Kook-Hwan (Department of Internal Medicine, Seoul National University Hospital)
Kim, Yon Su (Department of Internal Medicine, Seoul National University Hospital)
Han, Jin Suk (Department of Internal Medicine, Seoul National University Hospital)
Kim, Tae Min (Department of Internal Medicine, Seoul National University Hospital)
Lee, Se-Hoon (Department of Internal Medicine, Seoul National University Hospital)
Joo, Kwon-Wook (Department of Internal Medicine, Seoul National University Hospital)
Publication Information
The Korean journal of internal medicine / v.29, no.1, 2014 , pp. 40-48 More about this Journal
Abstract
Background/Aims: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. Methods: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. Results: One hundred and fifty-five patients (mean age, $58.7{\pm}12.6$ years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. Conclusions: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.
Keywords
Acute kidney injury; Proteinuria; Sunitinib;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Boehm S, Rothermundt C, Hess D, Joerger M. Antiangiogenic drugs in oncology: a focus on drug safety and the elderly: a mini-review. Gerontology 2010;56:303-309.   DOI
2 Gurevich F, Perazella MA. Renal effects of anti-angiogenesis therapy: update for the internist. Am J Med 2009;122:322-328.   DOI   ScienceOn
3 Maharaj AS, D'Amore PA. Roles for VEGF in the adult. Microvasc Res 2007;74:100-113.   DOI
4 Rini BI, Garcia JA, Cooney MM, et al. Toxicity of sunitinib plus bevacizumab in renal cell carcinoma. J Clin Oncol 2010;28:e284-e285.   DOI
5 Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol 2009;48:9-17.   DOI
6 Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368:1329-1338.   DOI   ScienceOn
7 Bhojani N, Jeldres C, Patard JJ, 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;53:917-930.   DOI   ScienceOn
8 Khan G, Golshayan A, Elson P, et al. Sunitinib and sorafenib in metastatic renal cell carcinoma patients with renal insufficiency. Ann Oncol 2010;21:1618-1622.   DOI
9 van Heeckeren WJ, Ortiz J, Cooney MM, Remick SC. Hypertension, proteinuria, and antagonism of vascular endothelial growth factor signaling: clinical toxicity, therapeutic target, or novel biomarker? J Clin Oncol 2007;25:2993-2995.   DOI
10 Launay-Vacher V, Deray G. Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs 2009;20:81-82.   DOI
11 Jhaveri KD, Flombaum CD, Kroog G, Glezerman IG. Nephrotoxicities associated with the use of tyrosine kinase inhibitors: a single-center experience and review of the literature. Nephron Clin Pract 2011;117:c312-c319.   DOI
12 Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115-124.   DOI   ScienceOn
13 Scartozzi M, Galizia E, Chiorrini S, et al. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol 2009;20:227-230.
14 Murukesh N, Dive C, Jayson GC. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer 2010;102:8-18.   DOI   ScienceOn
15 National Cancer Institute. NCI Term Browser: common terminology criteria for adverse events (CTCAE) version 4.03 [Internet]. Rockville (MD): National Cancer Institute, c2010 [cited 2010 Jun 14]. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html.
16 Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216.   DOI   ScienceOn
17 Patel TV, Morgan JA, Demetri GD, et al. A preeclampsia- like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J Natl Cancer Inst 2008;100:282-284.   DOI
18 Obhrai JS, Patel TV, Humphreys BD. The case/progressive hypertension and proteinuria on anti-angiogenic therapy. Kidney Int 2008;74:685-686.   DOI   ScienceOn
19 Kim HS, Hong MH, Kim K, et al. Sunitinib for Asian patients with advanced renal cell carcinoma: a comparable efficacy with different toxicity profiles. Oncology 2011;80:395-405.   DOI
20 Kelly RJ, Billemont B, Rixe O. Renal toxicity of targeted therapies. Target Oncol 2009;4:121-133.   DOI
21 Winn SK, Ellis S, Savage P, Sampson S, Marsh JE. Biopsy-proven acute interstitial nephritis associated with the tyrosine kinase inhibitor sunitinib: a class effect? Nephrol Dial Transplant 2009;24:673-675.
22 Khurana A. Allergic interstitial nephritis possibly related to sunitinib use. Am J Geriatr Pharmacother 2007;5:341-344.   DOI
23 Bollee G, Patey N, Cazajous G, et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant 2009;24:682-685.
24 Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management. Eur J Cancer 2010;46:439-448.   DOI   ScienceOn
25 Szmit S, Langiewicz P, Zlnierek J, et al. Hypertension as a predictive factor for survival outcomes in patients with metastatic renal cell carcinoma treated with sunitinib after progression on cytokines. Kidney Blood Press Res 2012;35:18-25.   DOI
26 Rini BI. Biomarkers: hypertension following anti-angiogenesis therapy. Clin Adv Hematol Oncol 2010;8:415-416.
27 Bono P, Elfving H, Utriainen T, et al. Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol 2009;20:393-394.
28 Oudard S, Beuselinck B, Decoene J, Albers P. Sunitinib for the treatment of metastatic renal cell carcinoma. Cancer Treat Rev 2011;37:178-184.   DOI
29 Rixe O, Billemont B, Izzedine H. Hypertension as a predictive factor of Sunitinib activity. Ann Oncol 2007;18:1117.   DOI
30 Machado FG, Kuriki PS, Fujihara CK, et al. Chronic VEGF blockade worsens glomerular injury in the remnant kidney model. PLoS One 2012;7:e39580.   DOI
31 Chen YS, Chen CL, Wang JS. Nephrotic syndrome and acute renal failure apparently induced by sunitinib. Case Rep Oncol 2009;2:172-176.   DOI
32 Kim HW, Lim JH, Kim MY, et al. Long-term blockade of vascular endothelial growth factor receptor-2 aggravates the diabetic renal dysfunction associated with inactivation of the Akt/eNOS-NO axis. Nephrol Dial Transplant 2011;26:1173-1188.   DOI   ScienceOn