RODENT MODEL OF SYSTEMIC MAMMARY-TUMOR DISEASE BY SURGICAL REMOVAL OFTHE SPONTANEOUSLY METASTASIZING SMT2A MAMMARY-CARCINOMA - INHIBITORY EFFECT OF THE STABLE PROSTACYCLIN ANALOG CICAPROST ON OCCULT METASTASIS

Cicaprost, a stable prostacyclin analogue, has been shown to be anti-m etastatically active in a series of metastasizing rodent tumors. Start of treatment with cicaprost immediately before tumor implantation was a characteristic feature of our previous investigations. We have repo rted that in rats bearing mammary-fat-pad-implanted SMT2A mammary carc inoma, cicaprost treatment starting before tumor implantation led to a strong decrease in the number of lung metastases. In order to determi ne the effect on occult tumor metastasis, the present study examined t he effect of starting treatment when tumor metastasis is already prese nt. Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to da y 32 reduced the number of lung metastases by about 75% compared with the control, whereas surgical removal of palpable primary tumors on da y 5 or day 10 failed to influence lung metastasis. Using different tre atment schedules, a pronounced reduction of the number of lung metasta ses was achieved by administration of cicaprost until the end of the e xperiment (from day 5 to day 35), whereas short-term treatments (from day 5 to day 15 or to day 25) were without significant effect. In rats whose SMT2A tumors were surgically removed 10 days after tumor implan tation, there was a strong decrease of lung metastases by cicaprost gi ven from day 20 to day 36. In addition to its inhibitory potential in animals with advanced tumor disease, cicaprost showed anti-metastatic action when used in peri-operative treatment of animals whose primary tumors had been removed. In conclusion, the present results demonstrat e that cicaprost exhibits strong antimetastatic activity in the SMT2A rat mammary-carcinoma model with treatment started when occult tumor m etastases are already present. Results also indicate that direct effec ts on tumor cells may contribute to the anti-metastatic action of cica prost in spontaneously metastasizing tumors. (C) 1995 Wiley-Liss, Inc.