Selective augmentations of intratumoral 5-fluorouracil concentration by local immunotherapy with OK-432 and fibrinogen

PURPOSE: Pyrimidine nucleoside phosphorylase is an enzyme that converts 5'- deoxy-5-fluorouridine into its active metabolite, 5-fluorouracil. In colore ctal cancer tissue: pyrimidine nucleoside phosphorylase has been proven to be produced by macrophages in the cancer stroma despite presence of the can cer cells. We reported that local immunotherapy with OK-432 and fibrinogen induced aggregation of macrophages in the cancer stroma and enforced their pyrimidine nucleoside phosphorylase expression. Thus it was hypothesized th at if colon cancer were treated with 5'-deoxy-5-fluorouridine, the 5-fluoro uracil concentration in. cancer tissues would be enhanced by local immunoth erapy. The present study was conducted to investigate whether local immunot herapy for colon cancer could increase the intratumoral 5-fluorouracil conc entration in patients given chemotherapy with 5'-deoxy-5-fluorouridine. MET HODS: Twenty patients with resectable colorectal cancer were examined in th is study. They were given 5'-deoxy-5-fluorouridine (600 mg/day) orally for seven days preoperatively. Nine randomly selected patients underwent intrat umoral injection of OK-432 mixed with fibrinogen, which was performed on th e third preoperative day (OK-432 and fibrinogen plus 5'-deoxy-5-fluorouridi ne group); eleven patients were given oral 5'-deoxy-5-fluorouridine only (5 '-deoxy-5-fluorouridine group). The 5-fluorouracil concentration in tumor t issue and normal colon mucosa tissue was measured, and the influence of the local immunotherapy was assessed. RESULTS: The 5-fluorouracil concentratio n in the cancer tissue was increased by the local immunotherapy, whereas th at in the normal colon mucosa was not influenced. Thus, the influence of lo cal immunotherapy was selective to the cancer tissue where the mixture of O K-432 and fibrinogen was injected. CONCLUSION: In patients with colorectal canter, selective high 5-fluorouracil concentration in the cancer tissue co uld be achieved by a combination of 5'-deoxy-5-fluorouridine and local immu notherapy with a mixture of OK-432 and fibrinogen.