Background: A Cochrane meta-analysis of randomised trials using histamine-type 2 receptor antagonists with surgery for colorectal cancer (CRC) demonstrated a hazard ratio of 0.53 for mortality if patients used cimetidine¹. The benefit is likely to be specific to patients whose tumours express the antigens that allow circulating cells to bind to endothelial selectin (E-selectin), the expression of which is induced by inflammatory cytokines perioperatively and inhibited by cimetidine. This trial sought to evaluate several key issues critical to informing the conduct of a phase 3 trial.

Methods: Patients with non-metastatic CRC planned for curative-intent surgery were randomised to receive cimetidine 800mg BID or placebo orally for 5 weeks, starting 2-7 days preoperatively. A subset of patients had serial blood sampling for inflammatory cytokines. In addition to DFS and OS, endpoints assessed include treatment compliance and toxicity, recruitment issues, post-operative stay and complications, and tumour characteristics including expression of sialyl Lewis antigens and COX-2.

Results: 123 patients (36% female) have been recruited in 4 centres over 3.5 years; another 5 are required to complete the planned 120 treated patients. The primary tumour was rectal in 45% and pathological postoperative tumour stage was 0-1, 2, 3 and 4 in 29%, 32%, 34% and 2% respectively. About 50% of CRC patients were eligible and fewer than half of those were recruited. Patient compliance was excellent with 89% of patients taking their medication orally in the first 2 days postoperatively. Inflammatory cytokines were commonly elevated postoperatively for up to 2 weeks but normalised by 4 weeks. Immunostaining for tumour antigens is in progress and will be presented. DFS and OS data are immature.

Conclusions: Oral administration of cimetidine for 5 weeks is well-tolerated and feasible over the perioperative period, and covers the duration of elevated inflammatory cytokines. Correlative immunostaining studies will be presented.