Successful re-challenge with panitumumab in patients who developed hypersensitivity reactions to cetuximab: report of three cases and review of literature
Successful re-challenge with panitumumab in patients who developed hypersensitivity reactions to cetuximab: report of three cases and review of literature
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DOI：
10.1007/s00280-008-0831-6
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发表时间：
2009-05-01
影响因子：
3
通讯作者：
Potter, Von
中科院分区：
文献类型：
--
作者：
Saif, Muhammad Wasif;Peccerillo, J.;Potter, Von
简介 靶向表皮生长因子受体 (EGFR) 的单克隆抗体 (MAb) 可有效治疗转移性结直肠癌 (mCRC)。西妥昔单抗是一种针对 EGFR 的嵌合单克隆抗体。即使进行术前用药，西妥昔单抗也可能引起超敏反应 (HSR)。如果出现严重的 HSR，则禁止进一步使用西妥昔单抗治疗，从而阻止这些患者接受潜在有益的抗 EGFR 治疗。帕尼单抗是一种完全人源 MAb，也靶向 EGFR。迄今为止，尚未检测到人类抗人抗体，并且与 CET 不同，HSR 很少发生，并且不需要术前用药。帕尼单抗对于既往曾接受西妥昔单抗治疗的严重 HSR 的患者的安全性尚不完全清楚。我们介绍了三名患有胃肠道癌症的患者，他们在西妥昔单抗经历了严重的 HSR 后，在没有 HSR 的情况下耐受了帕尼单抗。 患者和方法 三名患者在经历了西妥昔单抗标准剂量的 3 级 HSR 后，在严格观察和无术前用药的情况下接受了标准剂量的帕尼单抗 (6 mg/kg) 的挑战。第一位患者是一名患有 mCRC 的 58 岁男性，在接受第 8 剂西妥昔单抗期间出现 3 级 HSR。第二位患者是一名 58 岁女性，患有 mCRC，在第 12 剂西妥昔单抗期间出现 3 级 HSR。第三名患者是一名患有胰腺癌的 61 岁男性，在西妥昔单抗负荷剂量期间经历了 3 级 HSR。检查图表以查找既往过敏史，包括 H1 阻滞剂使用、药物过敏、蜂蜇过敏、湿疹、过敏反应性气道疾病或食物过敏。 结果 所有患者均为白种人，平均年龄 59 岁，无既往过敏史。没有患者接受任何术前用药。第一位患者接受帕尼单抗治疗 2 个月，第二位患者接受治疗 6 个月，第三位患者在 HSR 后 1 周再次接受西妥昔单抗治疗，治疗 6 个月后出现部分缓解。 结论 HSR 是与 MAb 相关的严重并发症。得益于杂交瘤技术，新一代单克隆抗体含有较少或不含小鼠特异性蛋白质序列，从而降低了 HSR 的风险。识别可能出现严重且有时危及生命的 HSR 的个体具有挑战性。我们报告了三名患者在西妥昔单抗出现严重 HSR 后成功接受帕尼单抗治疗，值得进一步研究。
Introduction Monoclonal antibodies (MAbs) targeting epidermal growth factor receptor (EGFR) are effective in treatment of metastatic colorectal cancer (mCRC). Cetuximab, a chimeric MAb targets EGFR. Even with premedication, cetuximab can cause a hypersensitivity reaction (HSR). In case of severe HSR, further therapy with cetuximab is contraindicated, thus preventing these patients from receiving potentially beneficial anti-EGFR therapy. Panitumumab is a fully human MAb also targets EGFR. To date, no human antihuman Ab have been detected, and unlike CET, HSR are infrequent, and no premedication is required. Safety of panitumumab in patients with a previous severe HSR with cetuximab is not fully known. We present three patients with GI cancers who tolerated panitumumab without HSR after experiencing severe HSR to cetuximab.Patients and methods Three patients were challenged with standard dose of panitumumab (6 mg/kg) after experiencing grade 3 HSR to standard dose of cetuximab under strict observation and no premedication. First patient, a 58-year- old male with mCRC developed grade 3 HSR during 8th dose of cetuximab. Second patient was a 58-year- old female with mCRC developed grade 3 HSR during 12th dose of cetuximab. Third patient was a 61-year-old male with pancreatic cancer who experienced grade 3 HSR during loading dose of cetuximab. Charts were reviewed to find history of prior allergy, including H1 blocker use, drug allergy, bee sting allergy, eczema, allergic reactive airways disease, or food allergy.Results All patients were Caucasians with an average age of 59 year with no history of prior allergy. No patient received any premedication. First patient received panitumumab for 2 months, second patient was treated for 6 months, and third patient who was rechallenged 1 week after HSR to cetuximab had a partial response following 6 months of therapy.Conclusions HSR are serious complications associated with MAbs. Thanks to hybridoma technology that newer generations of MAbs contain less or no mouse-specific protein sequences, hence reducing the risk of HSR. Identification of individuals likely to develop severe and sometimes life-threatening HSR is challenging. Our report of three patients successfully treated with panitumumab after they had severe HSR to cetuximab warrant further investigation.