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-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.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D004396:Coloring Agents / Q000493:pharmacokinetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D007267:Injections; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D051381:Rats; D011919:Rats, Inbred Strains; D012394:Rosaniline Dyes / Q000493:pharmacokinetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013052:Spectrometry, X-Ray Emission; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*