Much attention has recently focused on the role of
tumor cell-platelet interaction in the metastatic cascade.
Prostacyclin and stable
prostacyclin analogues have been shown to inhibit specifically the formation of
metastases in experimental
tumor models. This action is based on their ability to reduce the attachment of
tumor cells to platelets and to inhibit adhesion of
tumor cells-platelet aggregates to the endothelial lining. To investigate the antimetastatic potential of two
prostacyclin analogues (
Iloprost and
Eptaloprost, Schering AG), we have tested these compounds in the spontaneously metastasizing R 3327 MAT Lu prostate
carcinoma of the Cop rat in two types of experiments. Treatment was performed for 33 days, starting one day before s.c. implantation of the
tumor. The primary s.c.-implanted
tumor remained in situ throughout the experiment. In the first test,
Iloprost (0.3 micrograms/kg/min) and
Eptaloprost (0.1 micrograms/kg/min) were administered via Alzet mini pumps s.c.. There was a considerable reduction of the number of visible lung
metastases by
Eptaloprost. In the second test,
Eptaloprost was administered p.o. in doses of 0.1 and 0.5 mg/kg daily. The number of lung
metastases was significantly reduced. Both compounds had no effect on the growth of the primary
tumor in the first as well as in the second test. These data show that the
prostacyclin analogue
Eptaloprost has a significant antimetastatic activity in a spontaneously metastasizing
tumor model and thus merits further investigation.