Evaluation of the Effect and Side Effect of Tyrosine Kinase Inhibitors on the Treatment of Metastatic Renal Cell Carcinomas

Abstract

This study aims to retrospectively evaluate the efficacy and side effects of tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC). mRCC is a type of cancer diagnosed at advanced stages and significantly limits life expectancy. In Turkey, interferon-alpha has traditionally been used as a first-line treatment; however, targeted therapies such as TKIs have become a priority for patients showing progression. In the study, 65 patients who were diagnosed with mRCC and treated with TKI between 2010 and 2018 were examined. This retrospective analysis evaluated the demographic and clinical data of patients and their response to treatment. Key findings indicated that the survival outcomes of sunitinib and pazopanib treatments were consistent with the literature, with fatigue, hypertension, and dermatitis being prominent side effects. The average survival duration was calculated as 26 months. The results of the study support the effectiveness of TKIs in the treatment of mRCC and suggest that their impact could be better understood through prospective studies involving larger patient cohorts in the future.

Keywords

• Metastatic renal cell carcinoma
• Tyrosine kinase inhibitors
• VEGF inhibitors
• Prognostic factors
• Retrospective analysis

Metastatik Renal Hücreli Kanser Tedavisinde Tirozin Kinaz İnhibitörlerinin Etki ve Yan Etkisinin Değerlendirilmesi

Abstract

Bu çalışma, metastatik renal hücreli karsinom (mRHK) tedavisinde tirozin kinaz inhibitörlerinin (TKİ) etkinlik ve yan etkilerini retrospektif olarak değerlendirmeyi amaçlamaktadır. mRHK, ileri evrede tanı konulan ve yaşam süresi beklentilerini sınırlayan bir kanser türüdür. Türkiye'de interferon alfa tedavisi geleneksel olarak birinci basamak tedavi olarak uygulanmasına rağmen, progresyon gösteren hastalarda TKİ'ler gibi hedefe yönelik tedaviler öncelikli hale gelmiştir. Çalışmada, 2010-2018 yılları arasında mRHK tanısı almış ve TKİ tedavisi görmüş 65 hasta incelenmiştir. Bu retrospektif analizde, hastaların demografik ve klinik verileri ile tedaviye verilen yanıtlar değerlendirilmiştir. Ana bulgular arasında sunitinib ve pazopanib tedavilerinin sağkalım sonuçlarının literatürle uyumlu olduğu ve yan etkiler arasında halsizlik, hipertansiyon, dermatit gibi etkilerin öne çıktığı belirlenmiştir. Ortalama sağkalım süresi 26 ay olarak hesaplanmıştır. Çalışmanın sonuçları, TKİ’lerin mRHK tedavisindeki etkisini destekler nitelikte olup, gelecekte yapılacak daha geniş hasta gruplarını içeren prospektif çalışmalarla bu etkinliğin daha iyi anlaşılabileceği öne sürülmüştür.

Keywords

• Metastatik renal hücreli kanser
• Tirozin kinaz inhibitörleri
• VEGF inhibitörleri
• Prognostik faktörler
• Retrospektif analiz

References

1. 1.Bochner BH, Sjoberg DD, Laudone VP. A Randomized Trial ofRobot-Assisted Laparoscopic Radical Cystectomy. New England Journal of Medicine 2014;371(4):389–90.
2. 2.Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63(1):11–30.
3. 3.Hung T-W, Chen P-N, Wu H-C, et al. Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways. Int J Med Sci 2017;14(10):984–93.
4. 4.Berger A, Brandina R, Atalla MA, et al. Laparoscopic radical nephrectomy for renal cell carcinoma: oncological outcomes at 10 years or more. J Urol 2009;182(5):2172–6.
5. 5.Yagoda A, Petrylak D, Thompson S. Cytotoxic chemotherapy for advanced renal cell carcinoma. Urol Clin North Am1993;20(2):303–21.
6. 6.Robert J. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial.Medical Research Council Renal Cancer Collaborators. Lancet1999;353(9146):14–17.
7. 7.Latif F, Tory K, Gnarra J, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993;260(5112):1317–20.
8. 8.Kim WY, Kaelin WG. Role of VHL gene mutation in humancancer. J Clin Oncol 2004;22(24):4991–5004.

9. 9.Nickerson ML, Jaeger E, Shi Y, et al. Improved identificationof von Hippel-Lindau gene alterations in clear cell renaltumors. Clin Cancer Res 2008;14(15):4726–34.
10. 10.Chow W-H, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer. Nat Rev Urol 2010;7(5):245–57.
11. 11.Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR.Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008;113(1):78–83.
12. 12.Motzer RJ, Hutson TE, McCann L, et al. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl JMed 2014; 370:1769-74.
13. 13.Patard JJ, Leray E, Rioux-Leclercq N, et al. Prognostic value ofhistologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol 2005, 23 (12), 2763-71.
14. 14.Bianchi M, Sun M, Jeldres C, et al. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. AnnOncol 2012;23(4):973–80.
15. 15.Aron M, Nguyen MM, Stein RJ, Gill IS. Impact of gender inrenal cell carcinoma: an analysis of the SEER database. Eur Urol 2008;54(1):133–40.
16. 16.Wagener N, Edelmann D, Benner A, et al. Outcome of papillary versus clear cell renal cell carcinoma variessignificantly in non-metastatic disease. PLoS ONE 2017;12(9):e0184173.
17. 17.Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295(21):2516–24.
18. 18.Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versusinterferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–24.
19. 19.Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061–8.
20. 20.Cella D, Beaumont JL. Pazopanib in the treatment of advanced renal cell carcinoma. Ther Adv Urol 2016;8(1):61–9.
21. 21.Motzer RJ, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013;14(6):552–62.