Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma.

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.