직결장암 환자에서 Bevacizumab에 의한 단백뇨 발현과 치료효과와의 상관관계 분석
Correlation of Bevacizumab-induced Proteinuria with Therapeutic Effects in Patients with Colorectal Cancer
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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.
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.
참고문헌 (23)
- "Annual report of cancer statistics in Korea 2017"[URL]
- "Colorectal cancer"[URL]
- "Clinical Practice Guideline in OncologyTM, Colon cancer Version 3 (2020)"[URL]
- "Clinical Practice Guideline in OncologyTM, Rectal cancer Version 3" (2020)[URL]
- Hurwitz H, "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer", N Engl J Med, 350(23), pp.2335~2342 (2004)
- Saltz LB, "Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer : a randomized phase III study", J Clin Oncol, 26(12), pp.2013~2019 (2008)
- Van Cutsem E, "Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer", N Engl J Med, 360(14), pp.1408~1417 (2009)
- Bennouna J, "Continuation of bevacizumab after first progression in metastatic colorectal cancer(ML18147) : a randomised phase 3 trial", Lancet Oncol, 14(1), pp.29~37 (2013)
- Heinemann V, "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, 15(10), pp.1065~1075 (2014)
- "Micromedex solutions"[URL]
- Tanaka H, "Hypertension and proteinuria as predictive factors of effects of bevacizumab on advanced breast cancer in Japan", Biol Pharm Bull, 41(4), pp.644~648 (2018)
- Jane A, "Drug information handbook", pp.281~285 (2019), Wolters Kluwer
- Heo H, "Hypertension and clinical outcome in metastatic colorectal cancer patients treated with bevacizumab", J. Kor. Soc. Health-Syst. Pharm, 29(3), pp.324~337 (2012)
- Yan LZ, "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, 24(3), pp.209~217 (2018)
- Feliu J, "Correlation of hypertension and proteinuria with outcome in elderly bevacizumab-treated patients with metastatic colorectal cancer", PLoS One, 10(1), pp.e0116527~ (2015)
- Zhao T, "Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients : A systematic review and comprehensive meta-analysis", Oncotarget, 8(31), pp.51492~51506 (2017)
- Iwasa S, "Lack of association of proteinuria and clinical outcome in patients treated with bevacizumab for metastatic colorectal cancer", Anticancer Res, 33(1), pp.309~316 (2013)
- Uysal M, "Basal proteinuria as a prognostic factor in patients with metastatic colorectal cancer treated with bevacizumab", Biomed Pharmacother, 68(4), pp.409~412 (2014)
- Wolpin BM, "Systemic treatment of colorectal cancer", Gastroenterology, 134(5), pp.1296~1310 (2008)
- Van Cutsem E, "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, 30(28), pp.3499~3506 (2012)
- Wu S, "Bevacizumab increases risk for severe proteinuria in cancer patients", J Am Soc Nephrol, 21(8), pp.1381~1389 (2010)
- Lafayette R, "Incidence and relevance of proteinuria in bevacizumab-treated patients : pooled analysis from randomized controlled trials", Am J Nephrol, 40(1), pp.75~83 (2014)
- 김형종, "단백뇨의 감별진단 및 치료", 대한내과학회지, 85(4), pp.374~377 (2013), 대한내과학회[DOI]