FCE-27266, A SULFONIC DISTAMYCIN DERIVATIVE, INHIBITS EXPERIMENTAL AND SPONTANEOUS LUNG AND LIVER METASTASIS

FCE 27266, 2,2'-(carbonyl-bis[imino-N-methyl-4,2-pyrrole l-4,2-pyrrole }carbonylimino])-bis(1,5-naphthalene) disulfonic acid, is a noncytotox ic compound able to complex bFGF, PDGF beta, IL-8, VEGF and IL-1 beta and to inhibit the binding to their receptors. A single intravenous tr eatment 48 h prior to intravenous injection with tumor cells was assoc iated with 60% inhibition of lung metastasis from B16F10 murine melano ma and 82% inhibition of liver metastasis from M5076 murine reticulosa rcoma. Marginal inhibition was observed in the latter model, administe ring the drug 24 h after tumor cell injection. Efficacy was maintained in athymic mice, with 95 and 100% Inhibition of lung metastasis from B16F10 melanoma and A375 human melanoma. The antimetastatic activity w as confirmed in two models of spontaneous metastasis: in Lewis lung ca rcinoma implanted intramuscularly, daily intraperitoneal treatment fro m day 1 to 17 was associated with 77% inhibition of lung metastasis; o n M5076 reticulosarcoma implanted intramuscularly, daily intraperitone al treatment from day 1 to 14 prior to amputation of the tumor was ass ociated with significant inhibition of liver metastasis (79%); convers ely, daily intraperitoneal treatment from day 15 to 28 starting 1 day after amputation was marginally effective. The administered doses did not inhibit the growth of the primary tumor in both models. It is conc luded that FCE 27266 is a novel, promising molecule, with significant efficacy on lung and liver metastases of murine and human origin; its made of action is still under study and is probably exerted through in hibition of growth factors and cytokines influencing the different ste ps of angiogenesis and metastasis.