[Intra-arterial infusion chemotherapy combine with noradrenalin administration (an improved antitumor effect using a cancerous blood vessel]

We have performed experimental and clinical studies to observe whether higher concentrations of drugs are selectively delivered into tumor tissues through the tumor vessels and improved chemotherapy results were obtained by using noradrenaline in intraarterial chemotherapy. Noradrenaline administered into the tumor-feeding artery may enhance drug delivery into the tumor tissue and show improved chemotherapy results on Walker-256 formed tumor vessels. These advantages of using vasoconstrictive agents may be considered to be derived from the high injection pressure caused by increased vascular resistance and various other factors induced in abnormal microcirculation of the tumor vessels. MMC concentration in Walker-256 (weight 0.2 to 0.39 g) after intraarterial administration of 10 mg of MMC in 2.5 ml of physiological saline were 2.20 +/- 1.26 mcg/g (n = 11) in the noradrenaline group and 0.52 +/- 0.22 mcg/g (n = 13) in the MMC alone group. The 90-day survival ratio for intraarterial injection of 0.25 mg/kg of MMC and 2 mcg of noradrenaline was 42.9% (6/14), a result equivalent to a dose range of between 0.50 mg/kg and 0.75 mg/kg without the use of any vasoactive drug. The median survival periods for stomach cancer (Stage 4) after non-radical surgery by means of intraarterial chemotherapy with and without noradrenaline were, respectively, 12 months (n = 8) and 5.8 months (n = 6), with statistical significance (P greater than 0.05). Effective histological changes estimated microscopically by Takahashi's criteria of preoperative treatment in 31 stomach cancer patients were found in 11 patients (36.7%) with primary tumor and 12 patients (52.2%) with metastatic lymph nodes. A partial response rate of 54.5 (6/11) for hepatic tumor (Stages 3 to 4 according to was achieved with the use of the Ariel's classification) following regimen: intravenous injection of 70 mg/body of CDDP on the first day, followed by intraarterial injection of 0.1 to 0.4 mg/kg of MMC and 0.1 to 0.6 mg/kg of ADM together with 0.3 to 1.0 mg of noradrenaline in 40 to 100 ml of physiological saline for 3 to 20 minutes within one week after the first treatment. Most of the complications were due to hemorrhage from ulceration of the intestinal canal because of mucosal damage caused by the high concentration of anti-cancer drugs induced by noradrenaline. Decrease of hemoglobin of more than 1.0 g/dl was found in 19 out of 31 patients (61.3%) who received no treatment for bleeding, and in one out of 13 patients (7.7%) who was administered 200 mg of cimetidine twice a day for one week.