Reichle Albrecht, Grassinger Jochen, Bross Klaus, Wilke Jochen, Suedhoff Thomas, Walter Bernhard, Wieland Wolf-Ferdinand, Berand Anna, Andreesen Reinhard
Department of Hematology and Oncology, University Hospital of Regensburg.Department of Urology, University Hospital of Regensburg, Germany.
Biomark Insights. 2007 Feb 7;1:87-98.
Two consecutive multi-center phase II trials were designed to prove the hypothesis, whether therapeutic modeling of tumor-associated inflammatory processes could result in improved tumor response.Therapy in both trials consisted of low-dose capecitabine 1g/m2 twice daily p.o. for 14 days, every 3 weeks, day 1+, and rofecoxib 25 mg daily p.o., day 1+ (from 11/04 etoricoxib 60 mg daily instead) plus pioglitazone 60 mg daily p.o., day 1+. In study II low-dose IFN-alpha 4.5 MU sc. three times a week, week 1+, was added until disease progression.Eighteen, and 33 patients, respectively, with clear cell renal carcinoma and progressive disease were enrolled. Objective response (48%) was exclusively observed in study II (PR 35%, CR 13%), and paralleled by a strong CRP response after 4 weeks on treatment, p = 0.0005, in all 29 pts (100%) with elevated CRP levels. Median progression-free survival could be more than doubled from a median of 4.7 months (95% CI, 1.0 to 10.4) to 11.5 months (6.8 to 16.2) in study II, p = 0.00001. Median overall survival of population II was 26 months.Efficacious negative regulation of tumor-associated inflammation by transcription modulators may result in a steep increase of tumor response and survival.
两项连续的多中心II期试验旨在验证肿瘤相关炎症过程的治疗模式是否能改善肿瘤反应这一假设。两项试验的治疗方案均为：卡培他滨低剂量1g/m²，口服，每日两次，共14天，每3周重复，从第1天开始；罗非昔布25mg，口服，每日一次，从第1天开始（从2004年11月起改为依托考昔60mg，每日一次）；吡格列酮60mg，口服，每日一次，从第1天开始。在研究II中，低剂量干扰素α 450万单位，皮下注射，每周三次，从第1周开始，直至疾病进展。分别有18例和33例透明细胞肾癌和疾病进展患者入组。仅在研究II中观察到客观缓解（48%）（部分缓解35%，完全缓解13%），并且在所有29例（100%）C反应蛋白（CRP）水平升高的患者中，治疗4周后CRP反应强烈，p = 0.0005。在研究II中，无进展生存期的中位数从4.7个月（95%置信区间，1.0至10.4）增加到11.5个月（6.8至16.2），增加了一倍多，p = 0.00001。人群II的总生存期中位数为26个月。转录调节剂对肿瘤相关炎症的有效负调控可能会导致肿瘤反应和生存期急剧增加。
