Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Abstract

BackgroundThis phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction.MethodsPatients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS).ResultsA total of 24 patients were included. Four patients were treated at DL 1, 13 patients at DL 2 and 7 patients at DL 3. The MTD of the RCT was considered DL 2 with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2. Objective response (CR/PR) was observed in 32% (7/22) of patients. Eighteen patients (75%) underwent surgery after RCT. The median PFS for all patients (n = 24) was 6.5 months. The median overall survival for all patients (n = 24) was 16.3 months. Patients treated at DL 2 had a median overall survival of 29.5 months.ConclusionNeoadjuvant RCT with docetaxel 20 mg/m2 and oxaliplatin 50 mg/m2 was effective and showed a good toxicity profile. Future studies should consider the addition of targeted therapies to current neoadjuvant therapy regimens to further improve the outcome of patients with advanced cancer of the oesophagogastric junction.Trial RegistrationNCT00374985

Concurrent Neoadjuvant Chemoradiotherapy for Siewert II and III Adenocarcinoma at Gastroesophageal Junction

“…No other previous studies have found such results. 6 , 14 , 23 , 24 In addition, the pathological complete remission rate in this study was 16.7% and is consistent with previously reported results that ranged from 15% to 30%. 25 – 29 …”

“…However, the necessity for neoadjuvant therapy has not been confirmed. 12 – 14 Patients with adenocarcinoma of the gastroesophageal junction were not separated from those with esophageal, or gastric, cancer in most of these studies. The authors were able to identify on a few studies that seem to have been conducted investigating adenocarcinoma at the gastroesophageal junction.…”

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

“…Today, new neoadjuvant radio-chemotherapy regimens are under investigation. In a phase I/II trial, radiation with docetaxel and oxaliplatin in patients with advanced cancer of the esophagogastric junction appeared safe and showed efficacy with a median overall survival of 29.5 months in patients treated at the higher dose level (21). One option would be the addition of modern targeted therapies, such as EGFR antibodies, which resulted in significantly improved outcomes in patients irradiated for head-and-neck cancers (10,11).…”

Long‐term results of definitive concurrent chemoradiotherapy using paclitaxel plus oxaliplatin in unresectable locally advanced esophageal cancer: a prospective phase II trial

“…The profile of acute toxicity during CCRT was consistent with that reported in our previous phase II trial in the setting of PTX/platinum and irradiation 10. In another phase I/II study which assessed the safety of neoadjuvant chemoradiotherapy with docetaxel and OHP in patients with locally advanced adenocarcinoma of the esophagogastric junction, results also indicated that the treatment regimen based on docetaxel and OHP was effective and showed a good toxicity profile 16. Compared with CDDP‐based chemotherapy plus 60 Gy radiotherapy, our recent systemic review and pooled analysis which enrolled 1915 patients from 26 clinical studies also showed that the most common acute toxicities of grade 3 or higher for CDDP‐based CCRT were hematologic toxicities, the most severe grade 3 or higher radiation‐related acute toxicity was esophagitis, and the pooled incidence of esophagitis was 12.8% which was in line with this cohort 17.…”