An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer: The GC4 study
An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer: The GC4 study
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DOI：
10.1002/cncr.21814
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发表时间：
2006-05-01
期刊：
影响因子：
6.2
通讯作者：
Michaeli, D
中科院分区：
文献类型：
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作者：
Ajani, JA;Hecht, JR;Michaeli, D
背景胃泌素激素对体外培养的胃癌有促进作用，抗胃泌素抗体具有抗增殖和抗转移的作用。人类胃癌过度表达胃泌素基因和受体，对胃泌素的营养作用作出反应。免疫原G17 DT能特异性地激发高亲和力的阿加抗原。作者评价了G17 DT疫苗联合顺铂和5-氟尿嘧啶治疗胃腺癌的效果。在该多中心、II期研究中，患者在第1、5、9和25周肌内接受G17 DT疫苗接种，每28天接受顺铂加5-氟尿嘧啶。符合条件的患者患有未经治疗的转移性或不可切除的胃或胃食管腺癌，器官功能接近正常。该研究的主要终点是过度反应率（ORR），次要终点包括总生存期（OS）、安全性和成功接种疫苗对患者结局的影响。在5个国家共入组了103例患者。从分析中排除了7例因疏忽而过量使用5-氟尿嘧啶（严重违反方案）的患者。在79例接受缓解评价的患者中，确认的ORR为30%。中位疾病进展时间（TTP）为5.4个月，中位生存期（MS）为9.0个月（n = 96例患者）。94例接种疫苗的患者中有65例（69%）连续2次阿加滴度为2：1单位（成功接种疫苗的患者或免疫应答者）。免疫应答者的71，713比免疫无应答者长（P = 0.0005）。同样，免疫应答者的MS比免疫无应答者的MS长（10.3个月对3.8个月; P
BACKGROUND. Gastrin hormone is trophic to in vitro gastric cancer, and the antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human gastric cancers overexpress gastrin genes and receptors that react to gastrin's trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for the treatment gastric adenocarcinoma.METHODS. in this multicenter, Phase II study, patients received G17DT vaccination intramuscularly on weeks 1, 5, 9 and 25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had untreated, metastatic, or unresectable gastric or gastro-esophageal adenocarcinoma with near-normal organ function. The primary end-point of the study was the over response rate (ORR), and secondary endpoints included overall survival (OS), safety, and the impact of successful vaccination on patient outcome.RESULTS. In total, 103 patients were enrolled in 5 countries. Seven patients who were overdosed inadvertently with 5-fluorouracil (a major protocol violation) were removed from the analysis. The confirmed ORR was 30% in 79 patients who were evaluated for response. The median time-to-progression (TTP) was 5.4 months, and the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94 patients who were vaccinated (69%) had 2 consecutive AGA titers of 2:1 units (successfully vaccinated patients or immune-responders). The 71,713 was longer in immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8 months; P