IRL‐1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats

BACKGROUND IRL‐1620, a potent endothelin B receptor agonist, enhanced the efficacy of paclitaxel in a breast tumor model, but its effect in prostate cancer is not known. The present study was conducted to evaluate the effect of IRL‐1620 on tumor perfusion, uptake of [ 14 C]‐doxorubicin in the tumor and efficacy of doxorubicin (DOX), and 5‐flurouracil (5‐FU) in a rat prostate tumor model. METHODS JHU‐4 (Mat‐Lu) cells inoculated prostate tumor model in Copenhagen rats was used for the study. RESULTS Administration of IRL‐1620 (3 nmol/kg, i.v) significantly increased (102.8%) prostate tumor perfusion and tumor uptake of [ 14 C]‐doxorubicin (115%) compared to vehicle treated rats. Results of the efficacy study demonstrate that IRL‐1620 administration 15 min prior to DOX (5 mg/kg) or 5‐FU (50 mg/kg) on every third day for a total of four doses significantly reduced tumor volume compared to vehicle treated rats. CONCLUSIONS IRL‐1620 significantly enhanced the uptake and efficacy of anticancer agents in prostate cancer. Prostate 67: 701–713, 2007. © 2007 Wiley‐Liss, Inc.