8 例贝伐珠单抗致胃肠道穿孔的临床分析_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

周颖 ^1,2 , 芮元祎 ¹ , 许培培 ^1,2 , 杨琴 ^1,2 , 罗兴波 ^1,2 , 易波 ¹ ,  郑阳春 ¹

1. ;
2. ;

Corresponding author：

郑阳春, Email: dr_chunge@163.com

Keywords：

贝伐珠单抗; 胃肠道; 穿孔; 手术; 预后; 影响因素

DOI：

10.7507/1007-9424.202008117

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目的观察并分析接受贝伐珠单抗治疗的恶性肿瘤患者发生胃肠道穿孔的治疗方式及预后。方法回顾性分析 2013 年 1 月至 2019 年 11 月期间在四川省肿瘤医院接受贝伐珠单抗治疗后发生胃肠道穿孔的恶性肿瘤患者的临床资料，包括穿孔后的临床特征，贝伐珠单抗使用周期、单次使用剂量及累计剂量，骨髓抑制程度，感染情况，末次使用贝伐珠单抗至发生胃肠道穿孔的时间，穿孔后治疗方式、穿孔后生存时间等相关资料。结果共纳入 8 例患者的资料进行分析，分别是左半结肠癌 2 例，右半结肠癌 3 例，直肠癌、肺癌和子宫内膜癌各 1 例。8 例患者均有腹胀、腹痛症状，5 例患者出现严重腹膜炎（肌紧张、压痛、反跳痛），4 例患者出现膈下游离气体或腹腔游离气体。贝伐珠单抗中位使用次数为 2 次（1～16 次）、上下四分位数为（2，6），中位单次剂量为 0.4 g（0.3～0.4 g）、上下四分位数为（0.3，0.4），中位累计剂量为 0.8 g（0.4～4.8 g）、上下四分位数为（0.6，2.4），末次使用贝伐珠单抗至胃肠道穿孔的中位时间为 15 d（3～68 d）、上下四分位数为（4，16）。有 5 例患者接受手术治疗，穿孔至接受手术的中位时间为 34.5 h（2～72 h）、上下四分位数为（3.5，72.0）；3 例患者行保守治疗。2 例患者出现 Ⅳ 度骨髓抑制，6 例患者出现感染性休克、诊断为脓毒血症； 8 例患者经手术或保守治疗后相继死亡，中位死亡时间 23 d（15～37 d）、上下四分位数为（20，25）。结论接受贝伐珠单抗治疗的患者发生胃肠道穿孔的预后差，病死率高，在治疗过程中需密切关注相关并发症风险并在起病早期及早干预。

Citation： 周颖, 芮元祎, 许培培, 杨琴, 罗兴波, 易波, 郑阳春. 8 例贝伐珠单抗致胃肠道穿孔的临床分析. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(4): 516-519. doi: 10.7507/1007-9424.202008117 Copy

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6.	Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med, 2020, 382(20): 1894-1905.
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11.	Hatake K, Doi T, Uetake H, et al. Bevacizumab safety in Japanese patients with colorectal cancer. Jpn J Clin Oncol, 2016, 46(3): 234-240.
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13.	da Silva WC, de Araujo VE, Lima EMEA, et al. Comparative effectiveness and safety of monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) in combination with chemotherapy for metastatic colorectal cancer: a systematic review and meta-analysis. BioDrugs, 2018, 32(6): 585-606.
14.	Kabbinavar FF, Flynn PJ, Kozloff M, et al. Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study. Eur J Cancer, 2012, 48(8): 1126-1132.
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16.	程军. 贝伐珠单抗致器官穿孔41例文献分析. 中国医院药学杂志, 2017, 37(1): 58-61.
17.	李新明, 沈世强, 袁又能, 等. 直肠乙状结肠交界处肿瘤穿孔患者术后死亡相关因素的分析. 中华普通外科杂志, 2017, 32(4): 297-300.
18.	张权, 曲明阳. 结直肠癌所致大肠穿孔的临床特点分析. 大连医科大学, 2019.
19.	尚大可, 张慧力, 俞汉蒙. 结肠癌伴穿孔的术式研究. 中国现代医药杂志, 2017, 19(2): 32-35.
20.	陈红艳. 急性胃肠穿孔的急诊治疗探讨. 中国医药指南, 2017, 15(25): 83-84.
21.	于群, 李明, 刘影倩. 腹腔镜胃肠穿孔修补术治疗胃肠穿孔的疗效研究. 深圳中西医结合杂志, 2020, 30(10): 179-180.
22.	钟武, 刘传渊, 刘云庚, 等. 腹腔镜与开腹手术治疗结肠镜诊疗所致肠穿孔临床疗效的Meta分析. 结直肠肛门外科, 2019, 25(5): 584-591, 596.
23.	Badgwell BD, Camp ER, Feig B, et al. Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol, 2008, 19(3): 577-582.
24.	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): 2335-2342.
25.	Collins D, Ridgway PF, Winter DC, et al. Gastrointestinal perforation in metastatic carcinoma: a complication of bevacizumab therapy. Eur J Surg Oncol, 2009, 35(4): 444-446.

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
2. Pavlidis ET, Pavlidis TE. Role of bevacizumab in colorectal cancer growth and its adverse effects: a review. World J Gastroenterol, 2013, 19(31): 5051-5060.
3. von Minckwitz G, Puglisi F, Cortes J, et al. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol, 2014, 15(11): 1269-1278.
4. Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol, 2014, 15(11): 1236-1244.
5. Taal W, Oosterkamp HM, Walenkamp AM, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol, 2014, 15(9): 943-953.
6. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med, 2020, 382(20): 1894-1905.
7. Dudek AZ, Liu LC, Gupta S, et al. Phase Ⅰ b/Ⅱ clinical trial of pembrolizumab with bevacizumab for metastatic renal cell carcinoma: BTCRC-GU14-003. J Clin Oncol, 2020, 38(11): 1138-1145.
8. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003, 9(6): 669-676.
9. Gressett SM, Shah SR. Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother, 2009, 43(3): 490-501.
10. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol, 2007, 25(12): 1539-1544.
11. Hatake K, Doi T, Uetake H, et al. Bevacizumab safety in Japanese patients with colorectal cancer. Jpn J Clin Oncol, 2016, 46(3): 234-240.
12. Kozloff M, Yood MU, Berlin J, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist, 2009, 14(9): 862-870.
13. da Silva WC, de Araujo VE, Lima EMEA, et al. Comparative effectiveness and safety of monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) in combination with chemotherapy for metastatic colorectal cancer: a systematic review and meta-analysis. BioDrugs, 2018, 32(6): 585-606.
14. Kabbinavar FF, Flynn PJ, Kozloff M, et al. Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study. Eur J Cancer, 2012, 48(8): 1126-1132.
15. Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol, 2007, 14(6): 1860-1869.
16. 程军. 贝伐珠单抗致器官穿孔41例文献分析. 中国医院药学杂志, 2017, 37(1): 58-61.
17. 李新明, 沈世强, 袁又能, 等. 直肠乙状结肠交界处肿瘤穿孔患者术后死亡相关因素的分析. 中华普通外科杂志, 2017, 32(4): 297-300.
18. 张权, 曲明阳. 结直肠癌所致大肠穿孔的临床特点分析. 大连医科大学, 2019.
19. 尚大可, 张慧力, 俞汉蒙. 结肠癌伴穿孔的术式研究. 中国现代医药杂志, 2017, 19(2): 32-35.
20. 陈红艳. 急性胃肠穿孔的急诊治疗探讨. 中国医药指南, 2017, 15(25): 83-84.
21. 于群, 李明, 刘影倩. 腹腔镜胃肠穿孔修补术治疗胃肠穿孔的疗效研究. 深圳中西医结合杂志, 2020, 30(10): 179-180.
22. 钟武, 刘传渊, 刘云庚, 等. 腹腔镜与开腹手术治疗结肠镜诊疗所致肠穿孔临床疗效的Meta分析. 结直肠肛门外科, 2019, 25(5): 584-591, 596.
23. Badgwell BD, Camp ER, Feig B, et al. Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol, 2008, 19(3): 577-582.
24. 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): 2335-2342.
25. Collins D, Ridgway PF, Winter DC, et al. Gastrointestinal perforation in metastatic carcinoma: a complication of bevacizumab therapy. Eur J Surg Oncol, 2009, 35(4): 444-446.

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8 例贝伐珠单抗致胃肠道穿孔的临床分析

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