Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Correlation of Bevacizumab-induced Proteinuria with Therapeutic Effects in Patients with Colorectal Cancer

직결장암 환자에서 Bevacizumab에 의한 단백뇨 발현과 치료효과와의 상관관계 분석

  • Sa, Yea-Ji (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Kim, Kyung-Duck (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Ahn, Hye-Lim (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 사예지 (가톨릭대학교 서울성모병원 약제부) ;
  • 김경덕 (가톨릭대학교 서울성모병원 약제부) ;
  • 안혜림 (가톨릭대학교 서울성모병원 약제부)
  • Received : 2020.11.05
  • Accepted : 2020.12.07
  • Published : 2020.12.31
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Abstract

Background: Bevacizumab-induced proteinuria is known to occur when vascular endothelial cell receptors are blocked, which leads to decreased protein filtration. Although several studies have analyzed the correlation between therapeutic effect of bevacizumab and proteinuria, no conclusion has been established. Methods: In this retrospective study, colorectal cancer patients who received bevacizumab and urinary protein check from January 2015 to December 2016, were included. The incidence of proteinuria and the grade according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0 were evaluated after bevacizumab administration. The primary objective was to correlate proteinuria with overall response rate (ORR) and time to progression (TTP). Primary lesion, metastasized organs, surgery or radiation therapy, chemotherapy were investigated for analysis of risk factors for proteinuria development. Results: A total of 149 patients included in the analysis. Proteinuria occurred 19.5% (n=29) in the study patients; 20 in grade 1, 7 in grade 2, and 2 in grade 3. ORR was 55.2% in the proteinuria group and 51.7% in the non-proteinuria group. There was no difference between two groups (p=0.89). The TTP through the survival curve was similar in both groups (10 months, p=0.97). The risk of proteinuria was high in patients who had liver metastasis (p=0.02) and no surgery (p=0.01). Conclusions: These result indicates that bevacizumab-induced proteinuria expression was not correlated with the therapeutic effect on patients with colorectal cancer. Further analysis is required to find out the correlation between proteinuria and therapeutic effects. The risk of proteinuria was increased from patients who had liver metastasis, and no surgery.

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References

  1. Korea Central Cancer Registy, National Cancer Center: Annual report of cancer statistics in Korea 2017. Available from http://www.ncc.re.kr. Accessed July 20, 2020.
  2. National Cancer Information Center: Colorectal cancer. Available from http://www.cancer.go.kr. Accessed July 20, 2020.
  3. National Comprehensive Cancer Network. Clinical Practice Guideline in OncologyTM, Colon cancer Version 3 (2020). Available from http://www.nccn.org. Accessed July 20, 2020.
  4. National Comprehensive Cancer Network. Clinical Practice Guideline in OncologyTM, Rectal cancer Version 3 (2020). Available from http://www.nccn.org Accessed July 20, 2020.
  5. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-42. https://doi.org/10.1056/NEJMoa032691
  6. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26(12):2013-9. https://doi.org/10.1200/JCO.2007.14.9930
  7. Van Cutsem E, Kohne CH, Hitreet E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360(14):1408-17. https://doi.org/10.1056/NEJMoa0805019
  8. Bennouna J, Sastre J, Arnold J, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013;14(1):29-37. https://doi.org/10.1016/S1470-2045(12)70477-1
  9. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014;15(10):1065-75. https://doi.org/10.1016/s1470-2045(14)70330-4
  10. Micromedex solutions. IBM Watson Health, Greenwood Village, CO. Available from https://www.micromedexsolutions.com. Accessed July 20, 2020.
  11. Tanaka H, Takahashi K, Yamaguchi K, et al. Hypertension and proteinuria as predictive factors of effects of bevacizumab on advanced breast cancer in Japan. Biol Pharm Bull 2018;41(4):644-8. https://doi.org/10.1248/bpb.b17-00605
  12. Jane A, Joseph F, Roaa AG, et al. Drug information handbook 28th ed. North American: Wolters Kluwer, 2019; 281-5.
  13. Heo H, Choi JS, Im HJ, et al. Hypertension and clinical outcome in metastatic colorectal cancer patients treated with bevacizumab. J. Kor. Soc. Health-Syst. Pharm 2012;29(3):324-37. https://doi.org/10.32429/jkshp.2012.29.3.009
  14. Yan LZ, Dressler EV, Adams VR. Association of hypertension and treatment outcomes in advanced stage non-small cell lung cancer patients treated with bevacizumab or non-bevacizumab containing regimens. J Oncol Pharm Pract 2018;24(3):209-17. https://doi.org/10.1177/1078155217690921
  15. Feliu J, Salud A, Safont MJ, et al. Correlation of hypertension and proteinuria with outcome in elderly bevacizumab-treated patients with metastatic colorectal cancer. PLoS One 2015;10(1):e0116527. https://doi.org/10.1371/journal.pone.0116527
  16. Zhao T, Wang X, Xu T, Xu X, Liu Z. Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients: A systematic review and comprehensive meta-analysis. Oncotarget 2017;8(31):51492-506. https://doi.org/10.18632/oncotarget.18190
  17. Iwasa S, Nakajima TE, Nagashima K, et al. Lack of association of proteinuria and clinical outcome in patients treated with bevacizumab for metastatic colorectal cancer. Anticancer Res 2013;33(1):309-16.
  18. Uysal M, Bozcuk H, Göksu SS, et al. Basal proteinuria as a prognostic factor in patients with metastatic colorectal cancer treated with bevacizumab. Biomed Pharmacother 2014;68(4):409-12. https://doi.org/10.1016/j.biopha.2014.03.002
  19. Wolpin BM, Mayer RJ. Systemic treatment of colorectal cancer. Gastroenterology 2008;134(5):1296-310. https://doi.org/10.1053/j.gastro.2008.02.098
  20. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012;30(28):3499-506. https://doi.org/10.1200/JCO.2012.42.8201
  21. Wu S, Kim C, Baer L, Zhu X. Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol 2010;21(8):1381-9. https://doi.org/10.1681/ASN.2010020167
  22. Lafayette R, McCall B, Li N, et al. Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled analysis from randomized controlled trials. Am J Nephrol 2014;40(1):75-83. https://doi.org/10.1159/000365156
  23. Kim H. Differential diagnosis and treatment of proteinuria. Korean J Med 2013;85(4):374-7. https://doi.org/10.3904/kjm.2013.85.4.374