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 carbonyl-imino¿N-methyl-4,2-pyrrole¿carbonylimino])-bis- (1,5-naphthalene) disulfonic acid, is a noncytotoxic 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 treatment 48 h prior to intravenous injection with tumor cells was associated with 60% inhibition of lung metastasis from B16F10 murine melanoma and 82% inhibition of liver metastasis from M5076 murine reticulosarcoma. Marginal inhibition was observed in the latter model, administering 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 was confirmed in two models of spontaneous metastasis: in Lewis lung carcinoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 17 was associated with 77% inhibition of lung metastasis; on M5076 reticulosarcoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 14 prior to amputation of the tumor was associated with significant inhibition of liver metastasis (79%); conversely, 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 concluded that FCE 27266 is a novel, promising molecule, with significant efficacy on lung and liver metastases of murine and human origin; its mode of action is still under study and is probably exerted through inhibition of growth factors and cytokines influencing the different steps of angiogenesis and metastasis.