Systematic review of histamine type 2 receptor antagonists as an adjunct to curative surgical resection in gastrointestinal malignancies
e15085 Background: H2RAs have induced regression in a number of malignancies. The mechanisms that may contribute to this effect include inhibition of T-suppressor lymphocytes, increased tumor infiltrating lymphocytes and blockade of histamine-induced tumor proliferation and angiogenesis. Unique to cimetidine is its ability to inhibit vascular endothelial expression of the cell adhesion molecule E-selectin, to which many GI tumor cells adhere via carbohydrate antigen ligands. The optimal use of H2RAs in cancer patients could therefore be as adjuvant therapy rather than for metastatic disease. Methods: This systematic review examines the impact of H2RAs on the overall survival of patients when used as an adjunct to curative surgical resection for a GI malignancy. Using a sensitive search strategy, randomized controlled trials were identified in relevant databases. Criteria for study selection included: patients with colorectal or gastric cancer surgically resected with curative intent; H2RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for both the type of malignancy and the H2RA used and analyzed by meta-analysis using Cochrane Collaboration software. Results: Of 350 trials identified, 8 were eligible for inclusion and had sufficient data for analysis, including a total of 1461 patients. Meta-analysis revealed a risk ratio for mortality of 0.86 (95% CI 0.76–0.99, p = 0.03) for patients randomised to H2RAs. Trials of colorectal cancer patients where cimetidine was the H2RA being evaluated demonstrated a significant survival advantage, risk ratio 0.53 (95% CI 0.33–0.84, p = 0.007). All other subgroups demonstrated a non-significant trend favouring H2RAs. Conclusions: H2RAs, and cimetidine in particular, appear to confer a survival benefit when given as an adjunct to curative surgical resection of GI cancers. The trial designs were heterogeneous and further large studies are warranted. No significant financial relationships to disclose.