Increased hyperthermic response with prostaglandin E1 in VX2 liver carcinoma in rabbits

Most studies examining the potential of vasoactive drugs to selectively reduce the blood flow in a tumor and to enhance the thermal response to hyperthermia have used tumors growing in muscle tissues. We investigated the effect of prostaglandin E1 on a VX2 liver carcinoma in 95 female Japanese white rabbits. During continuous 20-minute intravenous infusions of prostaglandin E1 at doses of 1, 3, and 5 micrograms/kg per minute in rabbits with this liver tumor, the mean arterial blood pressure decreased to 81%, 74%, and 51% of initial levels, respectively. In the tumor, regional blood flow was 86%, 70%, and 56% of initial levels, respectively; in the adjacent liver tissue, it was 149%, 110%, and 86% of initial levels, respectively. The tumor and adjacent liver tissues were heated by a microwave generator, and the liver tissue was kept at 42.0 degrees C. The average temperature at the center of the tumor, which was 43.0 degrees C in the absence of prostaglandin E1, increased to 44.3 degrees C, 44.3 degrees C, and 44.2 degrees C when doses of 1, 3, and 5 micrograms/kg per minute were given, respectively. The therapeutic effect was determined on the basis of the tumor growth ratio (geometric tumor volume 7 days after treatment/volume at start of treatment). Hyperthermia alone resulted in a small reduction in the tumor growth ratio--from the control value of 11.82 to a value of 9.03. Hyperthermia combined with prostaglandin E1 led to an augmented reduction in tumor growth ratio (4.28, 4.70, and 4.79 during 1, 3, and 5 micrograms/kg per minute, respectively), compared with findings with hyperthermia alone. These results indicate that prostaglandin E1 reduces tumor blood flow, elevates tumor temperature during hyperthermia, and retards tumor growth after local heat treatment. For these reasons, prostaglandin E1 may be an effective adjuvant drug in clinical studies of hyperthermia in liver tumor.