Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial
Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial
复制标题
DOI：
10.1200/jco.2010.29.6244
复制
发表时间：
2010-10-01
影响因子：
45.3
通讯作者：
Kerr, David J.
中科院分区：
文献类型：
--
作者：
Midgley, Rachel S.;McConkey, Christopher C.;Kerr, David J.
目的实验室和病例对照研究表明环氧化酶-2 （COX-2）通路在结直肠癌发生中起关键作用。本研究的目的是测试COX-2抑制剂rofecoxib在结肠直肠癌（CRC）的辅助治疗中是否可以减少复发和提高生存率。患者和方法接受有可能治愈的II期和III期CRC手术并完成辅助治疗的患者随机分配接受罗非昔布（20mg /天）或安慰剂。主要终点为总生存期（OS）。在有福尔马林固定石蜡包埋肿瘤组织样本的情况下，通过免疫组织化学评估COX-2的表达并与临床结果相关。结果共纳入2434例患者。由于罗非昔布在全球范围内的停药，该试验被提前终止。在这一点上，1167名患者接受了罗非昔布治疗，1160名患者接受了安慰剂治疗，中位治疗时间分别为7.4个月和8.2个月。对于罗非昔布组和安慰剂组，中位随访时间分别为4.84年和4.85年，分别有241年和246人死亡，297年和329人复发。两组患者的OS（风险比[HR] = 0.97; 95% CI, 0.81 ~ 1.16; P = 0.75）和复发率（HR = 0.89; 95% CI, 0.76 ~ 1.04; P = 0.15）比较无差异。通过免疫组化对871例患者的肿瘤COX-2表达进行了评估，但没有观察到预后或预测效果。结论在本研究中，罗非昔布在CRC辅助治疗中的缩短治疗并没有改善未选择患者的OS或防止复发。此外，COX-2表达与预后总体无关，也不能预测COX-2抑制剂的有效性。
PurposeLaboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 ( COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC).Patients and MethodsPatients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome.ResultsTwo thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed.ConclusionIn this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors.