Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma
Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma
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DOI：
10.1007/s10637-006-5934-5
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发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Forastiere, AA
中科院分区：
文献类型：
--
作者：
Heath, EI;Burtness, BA;Forastiere, AA
目的：这项随机II期平行设计研究评估了术前联合治疗和基质金属蛋白酶（MMP）抑制剂priomastat对II期或以上可切除食管腺癌患者的治疗效果。该试验的目的是确定病理完全缓解率（pCR）、总缓解率、无进展生存期、疾病复发模式、两年生存期和总生存期。患者和方法：术前分期包括计算机断层扫描，内镜超声，可行时，腹腔镜检查。符合条件的患者被随机分配到术前普莫司他组或安慰剂组。加5-FU持续输注，顺铂，紫杉醇，同步放疗。第71天行食管切除术。所有研究患者均可使用辅助紫杉醇和普莫司他。结果：在2000年8月至2001年6月期间，计划78名患者中的15名被随机分配到试验中。随机分组后1例患者撤回同意。14例，每组7例。完成术前治疗和手术。在5例患者中实现了pCR: 1/7普莫司他和q7安慰剂。7例患者病情改善；5/7普莫司他和2/7安慰剂。在中位28个月的随访中，7名患者（2名普诺司他，5名安慰剂）存活，无疾病证据。原发性原发性巨噬细胞相关毒性为中度至重度肌肉骨骼毒性，干扰日常功能。这种毒性是通过治疗休息、减少剂量或停药来控制的。5名患者（3名普诺司他和2名安慰剂）发生危及生命的血栓栓塞事件，这导致对安全性和有效性的早期评估，随后终止了研究。结论：所有患者，无论治疗组，都能够成功地进行新辅助联合治疗和食管切除术。然而，由于意外的血栓栓塞事件，该研究提前结束，因此无法得出有关普诺伐他在局部晚期食管癌患者中的临床活性的结论。
Purpose: This randomized phase II, parallel-design study evaluated preoperative combined modality therapy and the matrix metalloprotease (MMP) inhibitor prinomastat in patients with resectable adenocarcinoma of the esophagus that were stage II or greater. The objectives of the trial were to determine pathologic complete response rate (pCR), overall response rate, progression-free survival, pattern of disease relapse, and two-year and overall Survival.Patients and Methods: Preoperative staging included computed tomography, endoscopic ultrasound, and, when feasible, laparoscopy. Eligible patients were randomized to preoperative prinomastat or placebo. plus continuous infusion 5-FU, cisplatin, paclitaxel, and Concurrent radiotherapy. Esophagectomy was performed on day 71. Adjuvant paclitaxel and prinomastat were available to all Study patients.Results: Between August 2000 and June 2001, 15 of a planned 78 patients were randomized into the trial. One patient after randomization withdrew consent. Fourteen patients, 7 in each arm. completed preoperative treatment and Surgery. pCR was achieved in 5 patients: 1/7 prinomastat and Q 7 placebo. Disease improvement was achieved in 7 patients; 5/7 prinomastat and 2/7 placebo. At a median follow-up of 28 months, 7 patients (2 prinomastat, 5 placebo) are alive with no evidence of disease. The primary prinomastat related toxicity was moderate to severe musculoskeletal toxicity interfering with daily function. This toxicity was managed with treatment rest, dose reduction, or discontinuation. Five patients (3 prinomastat and 2 placebo) had life-threatening thrombo-embolic events, which led to early evaluation of safety and efficacy, and subsequent termination of the Study.Conclusion: All patients, regardless of treatment arm, were able to successfully undergo neoadjuvant combined modality therapy and esophagectomy. However, early closure of the study due to unexpected thrombo-embolic events precluded any conclusions regarding clinical activity of prinomastat in locally advanced esophageal cancer patients.