胃癌患者术后应用贝伐珠单抗联合化疗的不良反应防治

Prevention of the adverse reaction application of bevacizumab in combination with chemotherapy in postoperative patients with gastric cancer

目的探讨胃癌患者术后应用贝伐珠单抗联合化疗所产生的不良反应，并提出相应的防治措施。方法选择2012年1月至2014年1月江门市中心医院收治的进展期胃癌根治术后应用贝伐珠单抗联合化疗的胃癌患者65例，其中男41例，女24例，中位年龄为48．7岁，观察其所产生的不良反应，并依据其不良反应情况给予相应防治措施，根据治疗效果结合临床及相关文献总结防治经验。结果胃癌患者术后应用贝伐珠单抗联合化疗引发的不良反应主要包括蛋白尿[共24例（37．0％），其中（＋）18例（27．8％），（＋＋）6例（9．2％）]、胃肠道反应[共10例（15．4％），其中Ⅰ级8例（12．3％），Ⅱ级2例（3．1％）]、血栓栓塞[共20例（30．7％），其中Ⅰ级13例（20％），Ⅱ级7例（10．7％）]及高血压[共11例（16．9％），其中Ⅰ级9例（13．8％），Ⅱ级2例（3．1％）]；术后贝伐珠单抗联合化疗治疗胃癌患者部分缓解41例（63．1％），稳定10例（15．4％），疾病进展14例（21．5％），总有效率63．1％。针对蛋白尿的不良反应，患者多见无症状性蛋白尿，若患者的尿蛋白检测结果为（＋）时，不进行特别处理，当患者的尿蛋白检测为（＋＋）时，给予观察，若患者尿蛋白≥2g／24h，则暂停贝伐珠单抗，直至尿蛋白〈2g。当患者出现消化系统损害时，多为ALT、AST升高，则进行保肝治疗，直至两种肝酶降至正常；患者的胃肠道反应多为恶心呕吐等，嘱患者清淡饮食，定期进行食管镜检查，若患者出现内脏器官瘘管则立即停用贝伐珠单抗。对有血栓栓塞的患者，应严密监测患者相关体征，一旦发现栓塞，不论任何级别的栓塞事件，均立即停用该化疗药物。对于高血压主要的不良反应，于患者用药前给予适当的药物讲解，减轻患者的恐惧、紧张感，避免情绪异常引起血压升高，患者用药期间应定期检测血压，若患者治疗期间发生血压急剧升高，则停用贝伐珠单抗，并进行降压治疗。结论临床医生应根据患者的实际情况，在对患者进行术后贝伐珠单抗联合化疗时对其可能发生的不同的不良反应进行相应的预估，并采取相应的防治措施，可以一定程度地避免严重不良反应的发生，提高患者生存质量。

Objective To investigate the adverse reaction of gastric cancer patients after inquiry application of bevacizumab combined with chemotherapy, and put forward some corresponding preventive measures. Methods Sixty-five cases patients with gastric cancer who were treated with advanced gastric cancer radical operation application of bevacizumab in combination with chemotherapy in the Central Hospital of Jiangmen from January 2012 to January 2014 ,including 41 male, 24 female, with the average age of 48.7 years old. The adverse reactions were observed, and give the corresponding prevention and control measures on the basis of the adverse reaction conditions, the experience in the prevention and treatment were summarized according to the therapeutic effect with clinical and related literature. Results The adverse reactions caused by bevacizumab combined with chemotherapy in patients with gastric cancer including proteinuria （a total of 24 cases（37%） ,including 18 cases（27.8%） of （＋） ,6 cases（9. 2%） of （＋ ＋）） ,gastrointestinal reaction（a total of 10 cases（15.4%） ,including 8 cases（ 12. 3%） of grade Ⅰ ,2 cases（3.1%） of grade Ⅱ ） ,thrombosis（a total of 20 cases （ 30.7 % ）, including 13 cases of grade Ⅰ （ 20% ）, 7 cases （ 10.7% ） of grade Ⅱ ） and hypertension （ a total of 11 cases（ 16. 9%） ,including 9 cases（13.8%） of grade Ⅰ ,2 cases（3.1%） of grade Ⅱ ）. Bevacizumab combined with chemotherapy in the treatment of gastric cancer patients with partial remission in 41 cases （63.1%）, 10 cases （15.4%） of stable disease progression, 14 cases （21.5%） of disease progression, the complete remission rate was 63.1%. For adverse reactions of proteinuria, patients with asymptomatic proteinuria, if patients with urinary protein detection results for （ ＋）, without special treatment, when patients with urinary protein detection for （ ＋ ＋）, given the observation, if patients with urinary protein was more than or equal to 2 g/ 24 h ,paused bevacizumab until proteinuria〈2 g. When the patients with digestive system damage, such as ALT and AST elevation, given the treatment of liver until the two hepatic enzymes returned to normal; patients with gastrointestinal reactions were nausea and vomiting, asked patient to light diet and regular esophagoscopy, if the patients appeared visceral fistula immediately stopped bevaeizumab. For patients with thrombosis, should be closely monitored in patients with signs, once found regardless of any level of embolism events, all immediately stopped the chemotherapy drugs. For the main adverse reactions of hypertension, given patients with proper medication explain before the treatment to reduce the fear, tension, and avoiding mood disorders which lead to an inerease in blood pressure, blood pressure should be regularly detected in patients who use drugs, if patients occurred a sharp rise in blood pressure during the treatment, immediately stopped bevacizumab and given antihypertensive treatment. Conclusion Clinicians should take the possible corresponding prediction in patients underwent application of bevaeizumab in combination with chemotherapy on the possible different adverse reactions according to the actual situation of patients, and take eorresponding preventive measures, can to some extent avoid serious adverse reaction occurred, and improve the quality of life of the patients.