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摘要:
目的 观察贝伐珠单抗（Bevacizumab，AVASTIN，Bev）与化疗药物联合治疗胃肠道肿瘤患者的不良事件，以便合理、安全的使用贝伐珠单抗，避免严重不良事件的发生。 方法 回顾性分析贝伐珠单抗（Bev）联合常规化疗治疗胃肠肿瘤77例，收集整理患者既往史，治疗前及治疗开始直至停止治疗后8周或死亡期间症状、体征和实验室检查，分析其在胃肠肿瘤患者治疗中的安全性。 结果 患者均为不能手术的局部进展期或转移性胃癌和结直肠癌，其中结直肠癌65例，胃癌12例，均采用贝伐珠单抗联合化疗。男性36例，女性41例，中位年龄49岁。77例患者中不良事件发生率为89.6%（69/77），3/4级不良事件（adverse even，AE）及严重不良事件（serious adverse even，SAE）发生率为26.0%（20/77）。分层分析不同情况下3/4级AE和SAE发生率，高龄组（≥65岁）为44.4%（4/9），低龄组（< 65岁）为23.5%（16/68）；男性为25%（9/36），女性为26.8%（11/41）；一线使用化疗联合贝伐珠单抗患者组为30.6%（11/36），二线及以上使用化疗联合贝伐珠单抗为22.0%（9/41），均无统计学差异。贝伐珠单抗联合两药化疗方案，其AE均以以血液学毒性和消化道反应（恶性、呕吐）为主，发生率50%~60%。贝伐珠单抗联合单药化疗AE发生率5%~8%。高血压、蛋白尿、出血及伤口愈合不良均为偶发、轻度。SAE 1例。 结论 贝伐珠单抗联合化疗治疗胃肠恶性肿瘤AE发生率无明显增加，性别、年龄以及使用贝伐珠单抗的时机（一线或二线及以上使用）等，其不良事件的发生率均无明显差异，贝伐珠单抗联合化疗治疗胃肠肿瘤患者耐受性良好。 Abstract:Objective To evaluate safety and efficacy of bevacizumab (AVASTIN) plus chemotherapy for the treatment of gastrointestinal cancer patients. Methods A retrospective study of 77 gastrointestinal (GI) cancer patients treated with bevacizumab plus chemotherapy was performed. Patient information collected included previous disease history, signs, synptom and homological and biochemical profiles. Patients were followed up for eight weeks after the last treatment or death. Statistical tests were used for subgroup analysis. Results All patients had locally advanced or metastatic GI cancer, who were not suitable for surgery. Their pathological diagnosis was adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma. Among these patients, there were 65 colorectal cancer patients and 12 gastric cancer patients. There were 36 male and 41 female patients with the median age of 49 years (26 ~ 76 years). The incidence of all adverse events among these 77 patients was 89.6 % (69 / 77). The incidence of adverse event (AE) with grade 3 / 4 and SAE was 26.0 % (20 / 77). Stratified analysis on AE with grade of 3 / 4 and SAE indicated that the incidence was 44.4 % (4 / 9) in old-age group (65 years old and older) and 23.5 % (16 / 68) in young-age group (younger than 65 years old). The incidence was 25 % (9 / 36) in male patients and 26. 0 % (11 / 41) in female patients. The incidence was 30.6 %(11 / 36) in the first-line therapy group and 22.0 % (9 / 41) in the second or later line therapy group. There was no statistical difference between each group. For patients treated with bevacizumab plus two-agent chemotherapy, the incidence of AE was 50 % ~ 60 % and most of them were hematological toxicity and gastrointestinal discomforts (such as nausea and vomiting). For bevacizumab combining with single-agent chemotherapy, the incidence of AEs was 5 % ~ 8 %. There were 4 cases of hypertension, 2 cases of proteinuria, 4 cases of bleeding, and 2 cases of delayed wound healing. There was 1 case of SAEs, which might be related to the studied drug. Conclusion The bevacizumab safety profile in this study was consistent with its safety profile in other clinical trials. The incidence of AE was not correlated with chemotherapy, gender or age. The bevacizumab related AE was rare and not accumulative with cytotoxic drug (s). -
Key words:
- Bevacizumab (AVASTIN) /
- Adverse event (AE) /
- Chemotherapy /
- Gastric cancer /
- Colorectal cancer
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表 1 患者临床资料
Table 1. Clinical data of patients
表 2 不良反应及严重不良事件发生率 例（%）
Table 2. Adverse Events
表 3 FOLFIRI+Bev不良事件（n=39） 例（%）
Table 3. Adverse events of FOLFIRI+Bev(n=39)
表 4 铂类联合化疗+Bev不良事件（n=28） 例（%）
Table 4. Adverse events of platinum+ Bev(n=28)
表 5 单药化疗+ Bev不良事件（n=24）例（%） 例（%）
Table 5. Adverse events of monotherapy+ Bev(n=24)
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