Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: A north central cancer treatment group phase II trial
Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: A north central cancer treatment group phase II trial
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DOI：
10.1200/jco.2004.05.034
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发表时间：
2004-12-15
影响因子：
45.3
通讯作者：
Fitch, TR
中科院分区：
文献类型：
--
作者：
Alberts, SR;Schroeder, M;Fitch, TR
目的吉西他滨仍是治疗转移性胰腺癌的标准药物，但活性有限。ISIS-2503是一种针对H-ras的反义化合物，在肿瘤模型中具有针对胰腺ACA的临床前活性。ISIS-2503和吉西他滨的组合已经在先前的I期研究中进行了评估。方法转移性或局部晚期胰腺ACA患者不适合手术或局部放射治疗，在第1天和第8天接受吉西他滨1,000 mg/m2静脉内输注30分钟，ISIS-2503 6 mg/kg/d连续静脉内输注14天，每3周为一个周期。每6 weeks.Results放射影像学反应进行了监测，48名符合条件的患者入组，43例转移性疾病。存活患者的中位随访时间为12.6个月（范围：2.2至16.8个月）。给予中位4个周期的治疗（范围，1至18个周期）。对所有患者的反应和毒性进行评估。6个月生存率为57.5%（95%CI，44.9%~ 73.5%），中位生存期为6.6个月。应答率为10.4%（1例完全应答，4例部分应答）。临床上显着的毒性是有限的，除了一个致命的肺embolis.Conclusion本研究显示了一个有希望的反应率，吉西他滨和ISIS-2503联合胰腺ACA患者。观察到这些患者的6个月生存率符合我们方案定义的成功标准。该方案是可以耐受的，但其益处尚不明确。应考虑评估吉西他滨和ISIS-2503在胰腺ACA治疗中的作用的其他研究。
Purpose Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study.Methods Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks.Results Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism.Conclusion This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.