A Prospective, Multicenter Phase II Study of the Efficacy and Feasibility of 15-minute Panitumumab Infusion Plus Irinotecan for Oxaliplatin- and Irinotecan-refractory, KRAS Wild-type Metastatic Colorectal Cancer (Short Infusion of Panitumumab Trial)
A Prospective, Multicenter Phase II Study of the Efficacy and Feasibility of 15-minute Panitumumab Infusion Plus Irinotecan for Oxaliplatin- and Irinotecan-refractory, KRAS Wild-type Metastatic Colorectal Cancer (Short Infusion of Panitumumab Trial)
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DOI：
10.1016/j.clcc.2017.10.004
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发表时间：
2018-03-01
影响因子：
3.4
通讯作者：
Shimada, Yasuhiro
中科院分区：
文献类型：
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作者：
Akiyoshi, Kohei;Hamaguchi, Tetsuya;Shimada, Yasuhiro
目前的前瞻性多中心II期研究是为了评估KRAS野生型奥沙利铂或伊立替康耐药的转移性结直肠癌患者较短15分钟Panitumab输注的可行性。研究结果表明，15分钟的Panitumab输注与以前的报道相似，没有输液相关的反应，也没有增加不良事件的频率和严重程度。背景：在最近更新的一些临床指南中，完全人源化的单抗Panitumab联合伊立替康已被推荐为KRAS野生型转移性结直肠癌(MCRC)的可选三线化疗。目前的前瞻性多中心II期研究评估了短期15分钟Panitumab输注的有效性和安全性。患者和方法：从2011年1月至2011年12月，在8个中心登记了KRAS野生型mCRC患者。关键的合格标准是年龄=20岁以及对伊立替康、氟嘧啶和奥沙利铂耐药或不耐受。所有患者接受6 mg/kg的Panitumumab和150 mg/m(2)或先前耐受剂量的伊立替康，每两周一次，直到疾病进展或不可接受的毒性。最初的Panitumab输液是60分钟，然后是30分钟的输液，然后是15分钟的输液。主要终点是使用实体肿瘤反应评估标准确认的应答率，1.0版。次要终点是无进展生存期、总生存期和毒性。该试验已在大学医院医学信息网临床试验登记处注册(UMIN编号000004647)。结果：43例患者中，中位年龄62岁(32~75岁)，男性58%，东部合作肿瘤组功能状态为0~1，总有效率37.2%(95%可信区间23.0~53.3)，确认有效率18.6%(95%可信区间8.4~33.4)。中位无进展生存期为5.8个月(95%CI，3.3~8.4个月)，总生存期为13.6个月(95%CI，10.8~16.5个月)。最常见的3/4级毒性是厌食症(12%)、白细胞减少(9%)和中性粒细胞减少(9%)。9名患者没有达到15分钟的输液时间，主要是因为疾病的进展。未观察到输液相关反应。结论：在KRAS野生型、奥沙利铂和伊立替康耐药的mCRC患者中，短时15分钟的Panitumab方案耐受性良好，且不影响安全性和有效性。
The present prospective, multicenter phase II study was conducted to evaluate the feasibility of shorter, 15-minute panitumumab infusions in patients with KRAS wild-type oxaliplatin-or irinotecan-refractory metastatic colorectal cancer. The findings indicate that 15-minute panitumumab infusions has efficacy similar to that in previous reports, with no infusion-related reactions or increases in the frequency or severity of adverse events.Background: In some recently updated clinical guidelines, the fully humanized monoclonal antibody panitumumab, combined with irinotecan, has been recommended as an optional third-line chemotherapy for KRAS wild-type metastatic colorectal cancer (mCRC). The present prospective, multicenter phase II study evaluated the effectiveness and safety of short 15-minute panitumumab infusions. Patients and Methods: From January 2011 to December 2011, patients with KRAS wild-type mCRC were enrolled at 8 centers. The key eligibility criteria were age >= 20 years and resistance or intolerance to irinotecan, fluoropyrimidine, and oxaliplatin. All patients received 6 mg/kg of panitumumab and 150 mg/m(2) or the previous tolerated dose of irinotecan, biweekly, until disease progression or unacceptable toxicity. The initial panitumumab infusion was 60 minutes, followed by a 30-minute infusion and then 15-minute infusions. The primary endpoint was the confirmed response rate using Response Evaluation Criteria In Solid Tumors, version 1.0. The secondary endpoints were progression-free survival, overall survival, and toxicity. The trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN no. 000004647). Results: Of the 43 patients, the median age was 62 years (range, 32-75 years), 58% were male, and the Eastern Cooperative Oncology Group performance status was 0 to 1. The total response rate was 37.2% (95% confidence interval [CI], 23.0-53.3), and the confirmed response rate was 18.6% (95% CI, 8.4-33.4). The median progression-free and overall survival were 5.8 months (95% CI, 3.3-8.4 months) and 13.6 months (95% CI, 10.8-16.5 months), respectively. The most frequent grade 3/4 toxicities were anorexia (12%), leukopenia (9%), and neutropenia (9%). Nine patients did not reach the 15-minute infusion, primarily because of disease progression. No infusion-related reactions were observed. Conclusion: The short 15-minute panitumumab infusion regimen was well tolerated, without compromising safety or efficacy in patients with KRAS wild-type, oxaliplatin-and irinotecan-refractory mCRC.