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重点关注转移性结直肠癌的 panitumumab。

Spotlight on panitumumab in metastatic colorectal cancer.

机构信息

Adis, a Wolters Kluwer Business, Auckland, New Zealand.

出版信息

BioDrugs. 2010 Aug 1;24(4):275-8. doi: 10.2165/11205460-000000000-00000.

Abstract

Panitumumab (Vectibix) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This spotlight reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacologic properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumors. The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicenter, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumors; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumors, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy (FOLFOX4) than with FOLFOX4 alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumors, but not in those with mutant KRAS tumors. Intravenous panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity. In conclusion, in patients with wild-type KRAS tumors, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.

摘要

帕尼单抗(Vectibix)是一种重组的、完全人源化的 IgG2 抗表皮生长因子受体(EGFR)单克隆抗体。本文重点介绍了静脉用帕尼单抗联合化疗治疗转移性结直肠癌一线和二线治疗,以及作为化疗耐药转移性结直肠癌的单药治疗的临床疗效,并总结了其药理学特性和耐受性。帕尼单抗适用于野生型而非突变型 KRAS 肿瘤患者。在转移性结直肠癌患者的随机、开放标签、多中心 III 期试验中,评估了每 2 周静脉给予 6mg/kg 帕尼单抗的疗效。作为一线或二线治疗联合化疗时,在野生型 KRAS 肿瘤患者中,帕尼单抗联合化疗显著延长无进展生存期,与单纯化疗相比差异有统计学意义;二线治疗试验中未观察到总生存期的显著组间差异。在突变型 KRAS 肿瘤患者中,与单独使用 FOLFOX4 相比,一线治疗试验中,帕尼单抗联合奥沙利铂为基础的化疗(FOLFOX4)的无进展生存期显著缩短,而二线治疗试验中,接受帕尼单抗联合伊立替康为基础的化疗(FOLFIRI)与单独接受 FOLFIRI 的患者之间无显著差异。在化疗耐药的转移性结直肠癌患者中,帕尼单抗单药联合最佳支持治疗显著延长无进展生存期,与单独最佳支持治疗相比差异有统计学意义,在总体人群和野生型 KRAS 肿瘤患者中均如此,但在突变型 KRAS 肿瘤患者中无显著差异。静脉用帕尼单抗单药或联合化疗治疗的耐受性良好。它与 EGFR 抑制剂相关的皮肤毒性特征有关,且似乎免疫原性风险低。总之,在野生型 KRAS 肿瘤患者中,帕尼单抗联合化疗是转移性结直肠癌一线和二线治疗的有效选择,或作为化疗耐药转移性结直肠癌的单药治疗。

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