Prophylactic antimetastatic treatment with aryldimethyltriazenes as adjuvants to surgical tumor removal in mice bearing Lewis lung carcinoma.

The effects of two benzenoid dimethyltriazenes (1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt [DM-COOK] and 1-p-tolyl-3,3-dimethyltriazene), which have been previously shown to reduce the formation of spontaneous lung metastases in mice bearing subcutaneous Lewis lung carcinoma, have been investigated in mice implanted im with the same tumor in the calf of the hind leg. Primary tumor was removed surgically by amputation in mice treated with the tested compounds preoperatively, and the survival time of the animals was then determined. A high rate of cures, ranging from 23\% to 43\%, has been observed when the treatment consisted of eight or three daily doses prior to tumor removal; a single immediately preoperative dose was less effective and caused a 10\% cure rate. Survival time of uncured mice was also significantly increased, particularly by DM-COOK. The division of the dose into two daily injections did not modify the activity of the triazenes, thus indicating that the antimetastatic coverage between two subsequent doses is not limited by fast pharmacokinetics or decomposition of the drugs. These results show that, at least in one animal system, aryldimethyltriazenes can be used also on palpable tumors as prophylactic adjuvants to surgery in order to reduce preoperative and intraoperative tumor spread.