Burris H A, Moore M J, Andersen J, Green M R, Rothenberg M L, Modiano M R, Cripps M C, Portenoy R K, Storniolo A M, Tarassoff P, Nelson R, Dorr F A, Stephens C D, Von Hoff D D
Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78245, USA.
J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer.
One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival.
Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated.
This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.
大多数晚期胰腺癌患者会经历疼痛，且由于肿瘤相关症状而不得不限制日常活动。迄今为止，尚无治疗方法对该疾病产生显著影响。在吉西他滨的早期研究中，胰腺癌患者的疾病相关症状有所改善。基于这些发现，进行了一项确定性试验，以评估吉西他滨对新诊断的晚期胰腺癌患者的有效性。
126例有症状的晚期胰腺癌患者完成了一个导入期，以确定疼痛特征并使其稳定，然后被随机分为两组，一组接受吉西他滨1000mg/m²，每周1次，共7次，随后休息1周，之后每4周每周1次，共3次（63例患者），另一组接受氟尿嘧啶（5-FU）600mg/m²，每周1次（63例患者）。主要疗效指标是临床获益反应，它是疼痛（镇痛药用量和疼痛强度）、卡氏功能状态评分和体重测量值的综合指标。临床获益要求至少一个参数持续改善（≥4周）且其他参数无恶化。其他疗效指标包括缓解率、疾病进展时间和生存率。
接受吉西他滨治疗的患者中有23.8%出现临床获益反应，而接受5-FU治疗的患者中这一比例为4.8%（P = 0.0022）。吉西他滨治疗组和5-FU治疗组的中位生存时间分别为5.65个月和4.41个月（P = 0.0025）。吉西他滨治疗患者12个月时的生存率为18%，5-FU治疗患者为2%。治疗耐受性良好。
本研究表明，在缓解晚期有症状胰腺癌患者的一些疾病相关症状方面，吉西他滨比5-FU更有效。与5-FU治疗相比，吉西他滨在生存方面也有适度优势。
