Department of Surgery, the Mutual Aid Association for Teachers and Officials Sanraku Hospital, 2-5 Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
World J Gastroenterol. 2011 Oct 21;17(39):4440-4. doi: 10.3748/wjg.v17.i39.4440.
Treatment with bevacizumab, an antiangiogenic agent, in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan. Bevacizumab improves the survival of patients with metastatic colorectal cancer; however, it may lead to complications such as bleeding, which are sometimes fatal. Bevacizumab should be administered only after careful consideration because the potential risks of therapy outweigh its benefits. Therefore, pharmaceutical companies do not recommend bevacizumab therapy for patients with brain metastases. While some reports support the cautious use of bevacizumab, others report that it is not always necessary to prohibit its use in patients with metastases to the central nervous system (CNS), including the brain. Thus, bevacizumab therapy in colorectal cancer patients with brain metastases is controversial, and it is unclear whether brain metastases are a risk factor for intracranial hemorrhage during anti-vascular endothelial growth factor (VEGF) therapy. We report a 64-year-old man and a 65-year-old man with recurrent colorectal cancer without brain metastases; these patients developed multifocal and solitary intracranial hemorrhage, respectively, after the administration of bevacizumab. Our findings suggest that intracranial hemorrhage can occur even if the patient does not have brain metastases prior to bevacizumab treatment and also suggest that brain metastases are not a risk factor for intracranial hemorrhage with bevacizumab treatment. These findings also question the necessity of excluding patients with brain metastases from clinical trials on anti-VEGF therapy.
贝伐珠单抗是一种抗血管生成药物，用于治疗转移性或不可切除的结直肠癌患者，该药在日本获得批准还不足 4 年。贝伐珠单抗可延长转移性结直肠癌患者的生存期，但也可能导致出血等并发症，有时甚至危及生命。由于治疗的潜在风险大于获益，因此应慎重考虑是否使用贝伐珠单抗。因此，制药公司不建议有脑转移的患者使用该药。虽然一些报告支持谨慎使用贝伐珠单抗，但其他报告则表明，对于包括脑转移在内的中枢神经系统（CNS）转移的患者，并不总是需要禁止使用该药。因此，对于结直肠癌伴脑转移患者是否使用贝伐珠单抗治疗存在争议，脑转移是否是抗血管内皮生长因子（VEGF）治疗过程中发生颅内出血的危险因素尚不明确。我们报告了 2 例复发性结直肠癌且无脑转移的患者，分别在使用贝伐珠单抗后发生了多灶性和单发的颅内出血。我们的研究结果表明，即使在使用贝伐珠单抗治疗前患者没有脑转移，也可能发生颅内出血，而且脑转移不是贝伐珠单抗治疗引起颅内出血的危险因素。这些结果还质疑了将有脑转移的患者排除在抗 VEGF 治疗临床试验之外的必要性。
