Langerak Alan, River George, Mitchell Edith, Cheema Puneet, Shing Mona
Cancer Care Associates, Tulsa, OK 74104, USA.
Clin Colorectal Cancer. 2009 Jan;8(1):49-54. doi: 10.3816/CCC.2009.n.008.
Monoclonal antibodies against the epidermal growth factor receptor approved for treating metastatic colorectal cancer (mCRC) include cetuximab (a chimeric antibody) and panitumumab (a fully human antibody). Because these antibodies have differences in protein sequence, patients intolerant to one antibody might still tolerate the other. Four cases are presented from a US panitumumab compassionate-use program in which patients with mCRC who were intolerant to cetuximab received panitumumab.
Eligible patients had failed previous fluoropyrimidine therapy with oxaliplatin- and irinotecan-containing chemotherapy, had cetuximab intolerance (ie, experienced an infusion reaction), and were unable to participate in a panitumumab clinical trial. For each patient, individual Federal Drug Administration-approved single-patient treatment use Investigational New Drug- and Institutional Review Board-approved protocols were used, informed consent was obtained, and data were collected independently by the investigator.
All 4 patients (2 men, 2 women) had received previous bevacizumab and premedications before cetuximab administration. In response to cetuximab, all 4 patients experienced Common Terminology Criteria for Adverse Events grade 3 or grade 4 infusion-reaction symptoms, which required acute therapy. Time from cetuximab discontinuation to panitumumab administration ranged from 8 days to 5 months. Panitumumab monotherapy was administered at approximately 6 mg/kg every 2 weeks. Two patients received premedications before panitumumab use. No physician reported any infusion reaction to panitumumab. One patient had stable disease, and 3 patients had disease progression.
Though this small case series provides evidence that patients with mCRC intolerant to cetuximab can receive subsequent panitumumab monotherapy without experiencing infusion reactions, additional clinical testing is needed to definitively examine this finding.
获批用于治疗转移性结直肠癌(mCRC)的抗表皮生长因子受体单克隆抗体包括西妥昔单抗(一种嵌合抗体)和帕尼单抗(一种全人源抗体)。由于这些抗体在蛋白质序列上存在差异,对一种抗体不耐受的患者可能仍能耐受另一种。本文介绍了美国帕尼单抗同情用药项目中的4例病例,这些mCRC患者对西妥昔单抗不耐受,但接受了帕尼单抗治疗。
符合条件的患者先前接受含氟嘧啶、奥沙利铂和伊立替康的化疗均失败,对西妥昔单抗不耐受(即发生输注反应),且无法参加帕尼单抗临床试验。对于每位患者,均采用了美国食品药品监督管理局批准的单患者治疗用研究性新药及机构审查委员会批准的方案,获得了知情同意,并由研究者独立收集数据。
所有4例患者(2男2女)在使用西妥昔单抗前均接受过贝伐单抗治疗及预处理。针对西妥昔单抗,所有4例患者均出现了3级或4级不良事件通用术语标准的输注反应症状,需要进行紧急治疗。从停用西妥昔单抗到开始使用帕尼单抗的时间为8天至5个月。帕尼单抗单药治疗每2周给药一次,剂量约为6mg/kg。2例患者在使用帕尼单抗前接受了预处理。没有医生报告任何与帕尼单抗相关的输注反应。1例患者病情稳定,3例患者病情进展。
尽管这个小病例系列提供了证据,表明对西妥昔单抗不耐受的mCRC患者后续接受帕尼单抗单药治疗时不会出现输注反应,但仍需要进行更多的临床试验来明确验证这一发现。