Long-term effects of proglumide on resection of cardiac adenocarcinoma

Abstract

Patients with advanced stage cardiac adenocarcinoma have a very poor prognosis. Surgery is the first choice of treatment for this kind of patients. Peptide hormone gastrin is a recognized growth factor for gastric cancer, and gastrin receptor antagonist proglumide can block the effects of gastrin. The aim of this study was to investigate the actions of proglumide as an adjuvant treatment to improve the postoperative long-term survival rate of patients with cardiac adenocarcinoma. We performed a randomized, controlled study of gastrin receptor antagonist proglumide in 301 patients with cardiac adenocarcinoma after proximal subtotal gastrectomy. The oral dose of 0.4 g proglumide thrice daily preprandially was maintained for more than 5 years in 153 cases (proglumide treatment group). In the control group, 148 patients underwent operation only. In clinicopathologic features, there was no significant difference between the two groups (P>0.05). All patients were followed up during their lifetime, and the survival rates were analyzed combined with clinicopathologic factors by SPSS 11.5 statistical software. The 1, 3, 5 and 10-year survival rate of the patients was 88.4%, 48.8%, 22.6% and 13.4%, respectively. The 1, 3, 5 and 10-year survival rate of the proglumide treatment group was 90.2%, 49.7%, 26.8% and 17.6% compared to 86.5%, 48.0%, 18.2% and 8.9% of the control group. There was a significant difference between the two groups (P = 0.0460). The patients in proglumide treatment group had no obvious side effects after administration of the drug, and no definite hepatic and renal function damage was found. According to single factor log-rank analysis, the long-term survival rate was correlated with the primary tumor position (P = 0.0205), length of the tumor (P = 0.0000), property of the operation (P = 0.0000), histopathologic grading (P = 0.0003), infiltrating degree of the tumor (P = 0.0000), influence of lymph node metastasis (P = 0.0000), clinicopathologic staging (P = 0.0000) and administration of proglumide (P = 0.0460). Cox regression analysis demonstrated the infiltrating degree of tumor (P = 0.000), influence of lymph node metastasis (P = 0.039) and the clinicopathologic staging (P = 0.003) were independent prognostic factors. Administration of proglumide (P = 0.081), length of the tumor (P = 0.304), radical status of the resection (P = 0.224) and histopathologic types (P = 0.072) were not the independent prognostic factors. Proglumide is convenient to use with no obvious toxic side effects, and prolonged postoperative administration of proglumide as a postoperative adjuvant treatment can increase the survival rate of patients after resection of cardiac adenocarcinoma. Proglumide may provide a new effective approach of endocrinotherapy for patients with gastric cardiac cancer.