Kindler Hedy Lee, Friberg Gregory, Skoog Linda, Wade-Oliver Kurombi, Vokes Everett E
University of Chicago Medical Center, Illinois 60637-1470, USA.
Am J Clin Oncol. 2005 Aug;28(4):340-4. doi: 10.1097/01.coc.0000159558.19631.d5.
Colorectal cancers frequently overexpress the epidermal growth factor receptor. Gefitinib (Iressa), an inhibitor of the epidermal growth factor receptor tyrosine kinase, is synergistic with oxaliplatin in preclinical colon cancer models. The authors conducted a phase I/II trial of gefitinib plus oxaliplatin in patients with previously treated metastatic colorectal cancer. In the phase I portion, 14 patients received oxaliplatin 130 mg/m2 intravenously every 21 days and gefitinib orally daily at 1 of 2 dose levels: 250 mg/day (8 patients), and 500 mg/day (6 patients). There were no objective responses. Three patients (38%) in the 250-mg cohort experienced disease stabilization for a median of 12 weeks, and 1 patient in the 500-mg cohort had stable disease for 18 weeks. Nausea/vomiting and rash were dose limiting. The randomized phase II part of the trial, in which patients were to receive oxaliplatin with or without gefitinib, was canceled due to the inactivity of single-agent gefitinib observed in the phase I portion, and emergent phase III data regarding the minimal activity of single-agent oxaliplatin. The authors conclude that the combination of gefitinib plus oxaliplatin is inactive in advanced colorectal cancer.
结直肠癌常过度表达表皮生长因子受体。吉非替尼（易瑞沙）是一种表皮生长因子受体酪氨酸激酶抑制剂，在临床前结肠癌模型中与奥沙利铂具有协同作用。作者开展了一项吉非替尼联合奥沙利铂用于既往治疗过的转移性结直肠癌患者的I/II期试验。在I期部分，14例患者接受奥沙利铂130mg/m²静脉注射，每21天1次，吉非替尼口服，每日1次，采用2个剂量水平之一：250mg/天（8例患者）和500mg/天（6例患者）。未观察到客观缓解。250mg组有3例患者（38%）病情稳定，中位持续时间为12周，500mg组有1例患者病情稳定18周。恶心/呕吐和皮疹为剂量限制性毒性。该试验的随机II期部分，即患者接受奥沙利铂联合或不联合吉非替尼治疗，由于在I期部分观察到单药吉非替尼无效，以及出现关于单药奥沙利铂最小活性的III期数据，而被取消。作者得出结论，吉非替尼联合奥沙利铂在晚期结直肠癌中无活性。
