Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma

摘要: 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 esophagus that were stage II or greater. The objectives trial to determine pathologic complete response rate (pCR), overall rate, progression-free survival, pattern disease relapse, two-year survival. Patients Methods: Preoperative staging included computed tomography, endoscopic ultrasound, and, when feasible, laparoscopy. Eligible placebo, plus continuous infusion 5-FU, cisplatin, paclitaxel, concurrent radiotherapy. Esophagectomy was performed on day 71. Adjuvant paclitaxel available all patients. Results: Between August 2000 June 2001, 15 a planned 78 into trial. One patient after randomization withdrew consent. Fourteen patients, 7 each arm, completed treatment surgery. pCR achieved 5 patients; 1/ 4/ placebo. Disease improvement /7 2 At median follow-up 28 months, (2 prinomastat, placebo) are alive no evidence disease. primary related toxicity moderate severe musculoskeletal interfering daily function. managed rest, dose reduction, discontinuation. Five (3 had life-threatening thrombo-embolic events, which led early evaluation safety efficacy, subsequent termination study. Conclusions: All regardless able successfully undergo neoadjuvant esophagectomy. However, closure due unexpected events precluded any conclusions regarding clinical activity locally advanced esophageal cancer