Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer
Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer
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DOI：
10.3816/ccc.2006.n.030
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Kugler, John W.
中科院分区：
文献类型：
--
作者：
O'Connell, Michael J.;Sargent, Daniel J.;Kugler, John W.
背景资料：左旋咪唑联合5-氟尿嘧啶（5-FU）以前被证明可以显着减少肿瘤复发，并提高患者的生存期时，切除的III期结肠癌患者术后。随后的实验室研究证明，随着左旋咪唑浓度的增加，5-FU对人癌细胞系的细胞毒性直接呈剂量依赖性增强。本研究设计了一项临床试验，以测试左旋咪唑以其最大耐受剂量与5-FU为基础的化疗联合给药的价值。患者和方法：878例高危II/III期结肠癌患者接受了完全手术切除，根据已知的预后因素分层，并随机接受2种治疗方案之一：标准剂量左旋咪唑联合5-FU和甲酰四氢叶酸;或高剂量左旋咪唑联合相同的化疗。在一组患者中监测血清新蝶呤以评估免疫功能。结果如下：严重的呕吐和神经系统副作用需要减少左旋咪唑的剂量，这在高剂量左旋咪唑方案中是安全的。两种治疗方案之间的无病生存期、总生存期或血清新蝶呤水平无显著差异。结论：左旋咪唑联合5-FU和甲酰四氢叶酸以其最大耐受剂量给药不可能提高高危结肠癌患者手术辅助化疗的疗效。观察到高剂量左旋咪唑方案的严重胃肠道和神经系统副作用发生率很高。
Background: Levamisole combined with 5-fluorouracil (5-FU) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer. Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines. A clinical trial was designed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy. Patients and Methods: Eight hundred seventy-eight patients who had undergone complete surgical resection of high-risk stage II/III colon cancer were stratified by known prognostic factors and randomized to receive 1 of 2 treatment regimens: standard-dose levamisole combined with 5-FU and leucovorin; or high-dose levamisole combined with the same chemotherapy. Serum neopterin was monitored in a cohort of patients to evaluate immune function. Results: Severe vomiting and neurologic side effects required reduction in the dose of levamisole that could be safely administered on the high-dose levamisole regimen. There were no significant differences in disease-free survival, overall survival, or levels of serum neopterin between the treatment regimens. Conclusion: It was not possible to improve the efficacy of surgical adjuvant chemotherapy for patients with high-risk colon cancer by giving levamisole at its maximum tolerated dose in combination with 5-FU and leucovorin. High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen.