DOCTOR: A randomized phase II trial of preoperative cisplatin, 5-fluorouracil, and docetaxel with or without radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the esophagus and/or OG junction.

Abstract

TPS4145 Background: Surgery forms the mainstay of curative treatment for oesophageal and gastro-oesophageal junction adenocarcinoma (OAC). Preoperative chemotherapy (CTX) with or without concurrent radiotherapy (CRT) have resulted in modest improvements in outcome. Patients who demonstrate a histological response in the resected specimen following pre-operative therapy (CTX or CRT) have consistently better survival than non-responders. Recent data suggests that early metabolic response, assessed by FDG-PET scan performed 14+/-1 days after the start of CTX compared with a baseline PET scan, is predictive of a histological response and improved survival. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised OAC. Methods: 150 patients with resectable adenocarcinona of the oesophagus or GOJ will be registered and given 1 cycle of cisplatin and 5FU (CF). Patients will undergo a series of baseline tests including endoscopy, endoscopic ultrasound and 18FDG-PET. At Day 15 of the initial CF cycle the PET will be repeated. Patients with a PET response (≥ 35% reduction in SUVmax) to initial treatment will continue with CF as standard treatment prior to surgery. PET non-responders (< 35% reduction in SUVmax) will be randomized equally to receive either docetaxel, cisplatin and 5FU (DCF) or DCF plus radiatiotherapy. Following completion of the preoperative chemotherapy /chemoradiotherapy patients will have their cancer surgically removed. The primary end point is major histological response (<10% residual viable tumour) and secondary endpoints of progression-free and overall survival, toxicity, quality of life and feasibility of response-based therapy. Eligibility: T2 or greater tumours (by EUS or CT), or T1 tumours that are poorly differentiated, or T1 node positive, histologically proven invasive adenocarcinoma of the oesophagus or GOJ, technically resectable tumour which is sufficiently FDG avid on the initial PET staging scan. Status: Opened to accural 2009.