Ajani Jaffer A, Hecht J Randolph, Ho Linus, Baker Jackie, Oortgiesen Marga, Eduljee Arnavaz, Michaeli Dov
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2006 May 1;106(9):1908-16. doi: 10.1002/cncr.21814.
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.
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 gastroesophageal adenocarcinoma with near-normal organ function. The primary endpoint 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.
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 > or =1 units (successfully vaccinated patients or immune-responders). The TTP 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 < or =.0001). In a multivariate analysis, successful vaccination was an independent OS prognosticator (P = .0001). G17DT did not have an adverse effect on safety.
The results demonstrated that successful G17DT vaccination was correlated with longer TTP and MS. AGA response was an independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer is warranted.
胃泌素对体外培养的胃癌具有营养作用，抗胃泌素抗体（AGAs）具有抗增殖和抗转移作用。人类胃癌中胃泌素基因及其对胃泌素营养作用产生反应的受体过表达。免疫原G17DT可引发特异性且高亲和力的AGAs。作者评估了G17DT疫苗联合顺铂加5-氟尿嘧啶用于治疗胃腺癌的效果。
在这项多中心II期研究中，患者在第1、5、9和25周接受G17DT疫苗肌肉注射，每28天接受顺铂加5-氟尿嘧啶治疗。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，且器官功能接近正常。该研究的主要终点是总体缓解率（ORR），次要终点包括总生存期（OS）、安全性以及成功接种疫苗对患者预后的影响。
共有来自5个国家的103例患者入组。7例因意外过量使用5-氟尿嘧啶（严重违反方案）的患者被排除在分析之外。在79例接受疗效评估的患者中，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%）连续两次AGAs滴度≥1单位（成功接种疫苗的患者或免疫应答者）。免疫应答者的TTP比无免疫应答者更长（P = .0005）。同样，免疫应答者的MS比无免疫应答者更长（10.3个月对3.8个月；P≤.0001）。在多变量分析中，成功接种疫苗是独立的OS预后因素（P = .0001）。G17DT对安全性没有不良影响。
结果表明，成功接种G17DT疫苗与更长的TTP和MS相关。AGAs应答是独立的OS预后因素。有必要对G17DT在胃癌中的应用进行III期评估。
