Saif M Wasif, Longo Walter L, Israel Gary
Division of Medical Onclogy, Yale University School of Medicine, New Haven, CT 06520, USA.
Clin Colorectal Cancer. 2008 Mar;7(2):144-8. doi: 10.3816/CCC.2008.n.020.
Bevacizumab is the fi rst vascular endothelial growth factor-targeted agent shown to increase survival in patients receiving first- and second-line intravenous 5-FU-based chemotherapy for the treatment of metastatic colorectal cancer. Bevacizumab is typically well tolerated and its major side effects include hypertension, proteinuria, bleeding, gastrointestinal perforation and arterial thrombotic events. Although exfoliative dermatitis has been described as a side effect in 19% of patients, skin rash (type unspecified) has rarely been described in patients following infusion of bevacizumab. We recently reported the fi rst patient with colon cancer manifesting a correlation between rash and a positive drug response with bevacizumab. A 49-year old male with T3 N1 M1 rectal carcinoma received modified FOLFOX-6/bevacizumab, which he tolerated very well except for grade 2 skin rash related to bevacizumab. The rash continued to progress as the serum carcinoembryonic antigen decreased significantly. Computed tomography and positron emission tomography scan confirmed response to FOLFOX/bevacizumab. We therefore believe that this rash was linked to bevacizumab administration and correlated with response to therapy. Grade 1/2 rash has been described in patients after infusion of bevacizumab in initial phase I and II studies. Skin rash was observed in 34% and 46% of patients in the Kabbinavar's study receiving 5 mg/kg dose and 10 mg/kg respectively but no patient developed > grade 3 rash. This toxicity was not well described in pivotal phase III studies. On the other hand, acneiform rash occurs in > 90% patients who receive cetuximab and panitumumab, severity of which appears to be predictive of response. To our knowledge, this case report is the second report of possible correlation between rash and a positive drug response associated with bevacizumab and warrants further investigation of similar observation.
贝伐单抗是首个被证实可提高接受一线和二线基于静脉注射5-氟尿嘧啶化疗的转移性结直肠癌患者生存率的血管内皮生长因子靶向药物。贝伐单抗通常耐受性良好，其主要副作用包括高血压、蛋白尿、出血、胃肠道穿孔和动脉血栓形成事件。尽管19%的患者出现剥脱性皮炎作为副作用，但在输注贝伐单抗后的患者中很少有皮疹（未明确类型）的描述。我们最近报告了首例结肠癌患者，其皮疹与贝伐单抗的阳性药物反应相关。一名49岁男性患有T3 N1 M1直肠癌，接受改良FOLFOX-6/贝伐单抗治疗，除了与贝伐单抗相关的2级皮疹外，他耐受性良好。随着血清癌胚抗原显著下降，皮疹持续进展。计算机断层扫描和正电子发射断层扫描证实对FOLFOX/贝伐单抗有反应。因此，我们认为这种皮疹与贝伐单抗给药有关，并与治疗反应相关。在初始的I期和II期研究中，输注贝伐单抗后的患者出现了1/2级皮疹。在卡比纳瓦尔的研究中，分别接受5mg/kg剂量和10mg/kg的患者中，34%和46%出现了皮疹，但没有患者出现>3级皮疹。在关键的III期研究中，这种毒性没有得到很好的描述。另一方面，接受西妥昔单抗和帕尼单抗的患者中>90%出现痤疮样皮疹，其严重程度似乎可预测反应。据我们所知，本病例报告是第二例关于皮疹与贝伐单抗相关的阳性药物反应之间可能存在关联的报告，值得对类似观察进行进一步研究。
