Epinephrine enhances penetration and anti-cancer activity of local cisplatin on rat sub-cutaneous and peritoneal tumors

Despite the theoretical advantages of a high local concentration of anti-ca ncer drugs, local chemotherapy often fails to produce complete and lasting responses in experimental and human solid tumors. Experiments using Patent Blue dye showed that fluids diffused poorly into tumor mass when injected i nside or around s.c. rat tumors in rats. In the same way, Patent Blue dye d istributed poorly from the peritoneal cavity into the tumor nodules of rats with peritoneal carcinomatosis. The potent vasoconstrictor, epinephrine mg /kg of body weight was shown to facilitate the penetration of Patent Blue d ye into s.c. and peritoneal rat tumors. Platinum concentration evaluated by micro-PIXE in s,c, DHD/KI2/PROb colon tumors or by atomic absorption spect rometry in DHD/KI2/PROb peritoneal tumors was 4- to Ii-fold higher when epi nephrine was added to local cisplatin. Peri-tumoral or intra-tumoral inject ion of cisplatin (2 mg/kg) alone does not cure s.c. DHD/KI2/PROb colon tumo rs or GVIAI glioma tumors in ED IX rats. By contrast, a complete and lastin g cure of s.c. tumors was achieved regularly and without skin necrosis when epinephrine was added to intra-tumoral or peri-tumoral cisplatin. Rats wit h peritoneal-tumor nodules I to 2 mm in diameter, and insensitive to i.p. c isplatin alone, were cured when the anti-cancer drug was combined with epin ephrine. These experimental results could justify clinical trials using a c ombination of cisplatin and epinephrine in the treatment of locally growing solid tumors. Int. j. Cancer 81:779-784,1999. (C) 1999 Wiley-Liss, Inc.