Cicaprost, a stable
prostacyclin analogue, has been shown to be anti-metastatically 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 reported that in rats bearing mammary-fat-pad-implanted SMT2A mammary
carcinoma,
cicaprost treatment starting before
tumor implantation led to a strong decrease in the number of lung
metastases. In order to determine the effect on occult
tumor metastasis, the present study examined the effect of starting treatment when
tumor metastasis is already present.
Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to day 32 reduced the number of lung
metastases by about 75% compared with the control, whereas surgical removal of palpable primary
tumors on day 5 or day 10 failed to influence lung
metastasis. Using different treatment schedules, a pronounced reduction of the number of lung
metastases was achieved by administration of
cicaprost until the end of the experiment (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 implantation, there was a strong decrease of lung
metastases by
cicaprost given 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 demonstrate that
cicaprost exhibits strong anti-metastatic activity in the SMT2A rat mammary-
carcinoma model with treatment started when occult
tumor metastases are already present. Results also indicate that direct effects on
tumor cells may contribute to the anti-metastatic action of
cicaprost in spontaneously metastasizing
tumors.