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帕尼单抗:用于治疗转移性结直肠癌。

Panitumumab: in the treatment of metastatic colorectal cancer.

作者信息

Hoy Sheridan M, Wagstaff Antona J

机构信息

Wolters Kluwer Health, Adis, Auckland, New Zealand.

出版信息

Drugs. 2006;66(15):2005-14; discussion 2015-6. doi: 10.2165/00003495-200666150-00011.

DOI:10.2165/00003495-200666150-00011
PMID:17100412
Abstract

Panitumumab is a fully human immunoglobulin G2 monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is overexpressed in 25-77% of colorectal cancers. This overexpression is frequently associated with a poor prognosis. In a large, randomised, nonblind, multicentre phase III study in pretreated adult patients with metastatic colorectal cancer and EGFR staining in >or=1% tumour cells, panitumumab 6 mg/kg every 2 weeks plus best supportive care (BSC) was significantly (p < 0.0001) more effective in improving progression-free survival than BSC alone; recipients of panitumumab plus BSC had a 46% lower disease progression rate than those receiving BSC alone after a median follow-up of 19 weeks. Panitumumab 6 mg/kg every 2 weeks or 2.5 mg/kg/week, administered as monotherapy, produced partial response rates of 8-13% and stable disease rates of 21-30% in pretreated patients with metastatic colorectal cancer in three noncomparative, multicentre phase II studies. Preliminary phase II results also suggest a potential role for panitumumab as first-line therapy in combination with fluorouracil, folinic acid and irinotecan in patients with metastatic colorectal cancer. Panitumumab was generally well tolerated. Grade 3/4 skin-related toxicities were reported in 14% of patients receiving panitumumab plus BSC in the phase III study (versus 0% of patients receiving BSC alone). An analysis of pooled data found that high-affinity binding antibodies to panitumumab were detected in <1% of patients.

摘要

帕尼单抗是一种完全人源化的免疫球蛋白G2单克隆抗体,对表皮生长因子受体(EGFR)具有高度选择性,EGFR在25%-77%的结直肠癌中过度表达。这种过度表达通常与预后不良相关。在一项针对成年转移性结直肠癌预处理患者且肿瘤细胞EGFR染色≥1%的大型、随机、非盲、多中心III期研究中,每2周给予帕尼单抗6 mg/kg加最佳支持治疗(BSC)在改善无进展生存期方面显著(p<0.0001)优于单纯BSC;在中位随访19周后,接受帕尼单抗加BSC的患者疾病进展率比单纯接受BSC的患者低46%。在三项非对照、多中心II期研究中,每2周给予帕尼单抗6 mg/kg或每周给予2.5 mg/kg作为单药治疗,转移性结直肠癌预处理患者的部分缓解率为8%-13%,疾病稳定率为21%-30%。II期初步结果还表明,帕尼单抗在与氟尿嘧啶、亚叶酸和伊立替康联合用于转移性结直肠癌患者的一线治疗中可能发挥作用。帕尼单抗总体耐受性良好。在III期研究中,14%接受帕尼单抗加BSC的患者报告了3/4级皮肤相关毒性(而单纯接受BSC的患者为0%)。对汇总数据的分析发现,<1%的患者检测到针对帕尼单抗的高亲和力结合抗体。

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