Preoperative radiotherapy in combination with metronidazole for resectable gastric cancer: long-term results of a phase 2 study.

AIM: Surgery remains the main treatment of stomach carcinoma. Poor long-term survival mandates the study of other techniques. An original treatment scheme with preoperative radiotherapy and metronidazole as a radiosensitizer is reported here. METHODS: Between 1982 and 1988, MRRC RAMS carried out a prospective clinical trial of preoperative radiotherapy (20 Gy/5 days) in combination with metronidazole (given orally, 3 times, 5 gms per metre(2)). Of 91 patients who received preoperative radiotherapy, 67 patients were operated on with curative intent and were eligible for further analysis. RESULTS: Acute gastro-intestinal toxicity was significant but manageable without surgery delay in most cases. There were 4 postoperative deaths. Overall 5-year, 10-year survival and median survival were 46%, 36% and 46 months. Serosal and nodal involvement were the most significant adverse prognostic factors. Tumours confined to the gastric wall, node negative cases, middle and distal location, differentiated tumours, female sex and age more than 50 years were associated with relatively good long-term results: overall 5-year survival was 50% or better, overall 10-year survival was 40% or better. CONCLUSION: The combined treatment showed significant but manageable acute toxicity. The long-term results seem encouraging and support further investigations in multimodal treatment of gastric cancer.

A prospective, randomized trial of pre-operative and intraoperative radiotherapy versus surgery alone in resectable gastric cancer.

INTRODUCTION: Worldwide, gastric cancer remains one of the most common malignancies. Discouraging survival rates after surgical treatment promote the study of adjuvant therapy. A prospectively, randomized, controlled clinical trial was performed in order to determine whether pre-operative and intraoperative radiotherapy improves treatment results of gastrectomy for stomach carcinoma. METHODS: From 1993 to 1998, 112 patients were randomized and underwent exploratory laparotomy; among them 78 satisfied protocol requirements and entered in the trial. Patients in the experimental group were treated with pre-operative radiotherapy (20 Gy/5 days), gastrectomy and intraoperative radiotherapy (20 Gy using 8-12 electrons). Patients in the control group underwent surgery alone. RESULTS: Incidence and distribution of post-operative complications were similar in both groups except significantly higher incidence of pancreatitis after surgical treatment. No late radiation-related morbidity was registered. There was no significant difference in survival between the two treatment groups (Chi(2)=1.026, df=1, P=0. 311) as well as in N0 (Chi(2)=0.0029, df=1, P=0.956) and T1-2 subgroups (Chi(2)=0.1928, df=1, P=0.660). In contrast, combined treatment had marked survival advantage in more advanced stages: in the case of lymph-node involvement (Chi(2)=4.19, df=1, P=0.04) and extragastric tumour extension (Chi(2)=4.118, df=1, P=0.042). CONCLUSION: The proposed intensive treatment programme is feasible, shows good acute and late tolerance and has the potential to improve survival in patients with locally advanced gastric cancer.