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

Abstract

Despite the theoretical advantages of a high local concentration of anti‐cancer 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 inside or around s.c. rat tumors in rats. In the same way, Patent Blue dye distributed poorly from the peritoneal cavity into the tumor nodules of rats with peritoneal carcinomatosis. The potent vasoconstrictor, epinephrine (1 mg/kg of body weight) was shown to facilitate the penetration of Patent Blue dye into s.c. and peritoneal rat tumors. Platinum concentration evaluated by micro‐PIXE in s.c. DHD/K12/PROb colon tumors or by atomic absorption spectrometry in DHD/K12/PROb peritoneal tumors was 4‐ to 12‐fold higher when epinephrine was added to local cisplatin. Peri‐tumoral or intra‐tumoral injection of cisplatin (2 mg/kg) alone does not cure s.c. DHD/K12/PROb colon tumors or GV1A1 glioma tumors in BD IX rats. By contrast, a complete and lasting cure of s.c. tumors was achieved regularly and without skin necrosis when epinephrine was added to intra‐tumoral or peri‐tumoral cisplatin. Rats with peritoneal‐tumor nodules 1 to 2 mm in diameter, and insensitive to i.p. cisplatin alone, were cured when the anti‐cancer drug was combined with epinephrine. These experimental results could justify clinical trials using a combination of cisplatin and epinephrine in the treatment of locally growing solid tumors. Int. J. Cancer 81:779–784, 1999. © 1999 Wiley‐Liss, Inc.

Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study

“…It has been described that administration of anticancer agents immediately after tumor cell inoculation can eliminate all disease, whereas late administration (later than 3 days after tumor inoculation, when usually macroscopic disease is present) may slow down tumor growth but cannot be used with curative intent. [16][17][18][19][20] The current study shows, in accordance with the experimental literature mentioned, that the application of intraperitoneal chemotherapy 1 day after surgery is still effective to eliminate microscopic tumor cells after cytoreductive procedures, without use of hyperthermic circumstances. Twelve animals from the EPIC group and five animals from the HIPEC group were alive at the end of the follow-up period of 24 weeks.…”

Use of an Anti-Vascular Endothelial Growth Factor Antibody in a Pharmacokinetic Strategy to Increase the Efficacy of Intraperitoneal Chemotherapy

“…However, the high concentrations of glucose in dialysate solutions led to severe hyperglycemia, and it has been concluded that this adjunct therapy is not viable for clinical use. Duvillard et al (1999) investigated the effect of epinephrine on the penetration of cisplatin and patent blue dye into abdominal tumors after intraperitoneal dosing. They observed that epinephrine strongly enhanced the penetration of the dye into tumor nodules.…”

Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth

“…Epinephrine is a local vasoconstrictor commonly added to local anesthetic drugs and has recently been used in association with intratumoral and intraperitoneal chemotherapy for enhancement of tumor penetration and antitumoral activity. 39,40 In our experiments, epinephrine greatly enhanced intratumoral transfection rate without any toxicity at the concentration used (1 mg/l).…”