Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer
Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer
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DOI：
10.1007/s12094-011-0637-6
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发表时间：
2011-03-01
影响因子：
3.4
通讯作者：
Jimeno, Antonio
中科院分区：
文献类型：
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作者：
Gravalos, Cristina;Gomez-Martin, Carlos;Jimeno, Antonio
HER 2过表达和/或扩增存在于9-38%的胃癌或胃食管交界处（GEJ）癌中，并与不良结局相关。我们进行了一项多中心II期试验，以评估曲妥珠单抗联合顺铂治疗未经治疗的HER 2阳性晚期胃癌或GEJ癌患者的疗效。（IHC 3+或IHC 2+和FISH+）、年龄18岁、ECOG 1千分之一货币符号2、左心室射血分数1千分之一50%和适当的器官功能合格。治疗包括曲妥珠单抗（第1周期第1天8 mg/kg作为负荷;后续周期6 mg/kg）和顺铂（75 mg/m2），均在第1天静脉注射，每21天1次。228例患者中有22例（10%）为HER 2阳性，并被纳入该II期试验。中位年龄为66岁，ECOG 0/1为41%/59%。中位周期数为4（范围1-41）。确认的ORR为32%，64%的患者实现了疾病控制。中位进展时间为5.1个月。3级不良事件包括虚弱（27%）、中性粒细胞减少（18%）、厌食（14%）、腹泻（9%）和腹痛（9%）。未发生4级毒性或治疗相关死亡。基线HER细胞外结构域（ECD）水平越高，在反应和生存率方面的结果越好。曲妥珠单抗联合顺铂是一种有效的治疗方案，在晚期HER 2阳性胃癌或胃食管癌中具有良好的毒性。
HER2 over-expression and/or amplification are present in 9-38% of gastric or gastroesophageal junction (GEJ) cancers and are correlated to poor outcome. We conducted a multicentre phase II trial to evaluate trastuzumab in combination with cisplatin in patients with untreated HER2-positive advanced gastric or GEJ cancer.Chemo-na < ve patients with measurable, non-resectable, advanced or metastatic gastric or GEJ adenocarcinoma, with HER2 over-expression and/or amplification (IHC 3+, or IHC 2+ and FISH+), age a parts per thousand yen18 years, ECOG a parts per thousand currency sign2, left ventricle ejection fraction a parts per thousand yen50% and adequate organ function were eligible. Treatment consisted of trastuzumab (8 mg/kg on cycle 1 day 1 as loading; 6 mg/kg in subsequent cycles) and cisplatin (75 mg/m(2)), both intravenously on day 1, every 21 days.Twenty-two out of 228 patients (10%) were HER2-positive and were included in this phase II trial. The median age was 66 years and ECOG 0/1 was 41%/59%. The median number of cycles was 4 (range 1-41). The confirmed ORR was 32% and disease control was achieved in 64% of patients. Median time to progression was 5.1 months. Grade 3 adverse events included asthenia (27%), neutropenia (18%), anorexia (14%), diarrhoea (9%) and abdominal pain (9%). There were no grade 4 toxicities or treatment-related deaths. Higher baseline HER extracellular domain (ECD) levels were associated with better outcome in terms of response and survival.Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers.