Boorjian Stephen A, Berglund Ryan K, Maschino Alexandra C, Savage Caroline J, Herr Harry W
Section of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
J Urol. 2009 Oct;182(4):1306-12. doi: 10.1016/j.juro.2009.06.026. Epub 2009 Aug 14.
Studies suggest that the antitumor effect of bacillus Calmette-Guerin depends on bacillus Calmette-Guerin attachment to fibronectin at fibrin clot formation sites and medications that impact fibrin clot formation may modify bacillus activity. We evaluated the impact of fibrin clot inhibitors on the clinical efficacy of bacillus Calmette-Guerin.
We reviewed the records of 907 consecutive patients treated with bacillus Calmette-Guerin between 1990 and 2006. Time to disease recurrence and progression to surgery were compared in patients who did and did not receive fibrin clot inhibitors by Kaplan-Meier methods and multivariate Cox regression models.
Overall 221 patients (24%) received at least 1 fibrin clot inhibitor, including 170, 34 and 52 on aspirin, clopidogrel and warfarin, respectively. Patients on warfarin had shorter time to progression than patients not on warfarin (median 2.1 vs 9.0 years, p <0.005). Patients on aspirin had a significantly improved 5-year probability of freedom from surgery (66% vs 56%, p = 0.029). On multivariate analysis warfarin was associated with an increased risk of progression to surgery (HR 1.89, 95% CI 1.31, 2.74, p = 0.0007), while aspirin was associated with a decreased risk (HR 0.71, 95% CI 0.52, 0.96, p = 0.024). Warfarin alone was associated with an increased risk of tumor recurrence (HR 1.39, 95% CI 1.00, 1.94, p = 0.047).
These data suggest that the risks of recurrence and progression to surgery after bacillus Calmette-Guerin are higher in patients on warfarin, while the risk of progression is lower in patients on aspirin. These findings may have important treatment implications in patients in whom bacillus Calmette-Guerin is contemplated.
研究表明,卡介苗的抗肿瘤作用取决于卡介苗在纤维蛋白凝块形成部位与纤连蛋白的附着,而影响纤维蛋白凝块形成的药物可能会改变卡介苗的活性。我们评估了纤维蛋白凝块抑制剂对卡介苗临床疗效的影响。
我们回顾了1990年至2006年间连续接受卡介苗治疗的907例患者的记录。采用Kaplan-Meier方法和多变量Cox回归模型,比较了接受和未接受纤维蛋白凝块抑制剂的患者疾病复发时间和进展至手术的时间。
共有221例患者(24%)至少接受过1种纤维蛋白凝块抑制剂,其中分别有170例、34例和52例服用阿司匹林、氯吡格雷和华法林。服用华法林的患者进展时间比未服用华法林的患者短(中位时间2.1年对9.0年,p<0.005)。服用阿司匹林的患者5年免于手术的概率显著提高(66%对56%,p = 0.029)。多变量分析显示,华法林与进展至手术的风险增加相关(风险比1.89,95%置信区间1.31至2.74,p = 0.0007),而阿司匹林与风险降低相关(风险比0.71,95%置信区间0.52至0.96,p = 0.024)。单独使用华法林与肿瘤复发风险增加相关(风险比1.39,95%置信区间1.00至1.94,p = 0.047)。
这些数据表明,服用华法林的患者在接受卡介苗治疗后复发和进展至手术的风险较高,而服用阿司匹林的患者进展风险较低。这些发现可能对考虑使用卡介苗治疗的患者具有重要的治疗意义。