Renal chemoembolization with mitomycin c/Ethibloc: pharmacokinetics and efficacy in an animal model.
OBJECTIVE
Arterial embolization can be an alternative treatment for kidney malignancy. We investigated the efficacy of renal embolization with a combination of an occlusive agent (Ethibloc) and the cytotoxic substance mitomycin C (MMC) in an animal model.


METHODS
In 32 rats with implanted Yoshida sarcoma, nephrectomy was carried out 15, 30, 60, or 90 minutes after chemoembolization (1 mg v 2 mg of MMC/mL of Ethibloc) or chemoperfusion (1 mg of MMC/mL of NaCl) of the tumor-bearing kidney. The MMC tissue concentration was measured in the kidney specimens. Six dogs also underwent chemoembolization or chemoperfusion with monitoring of MMC serum concentration at the same intervals. We compared the survival time of rats with Yoshida sarcoma after chemoembolization (N = 15), chemoperfusion (N = 18), embolization (N = 18), nephrectomy (N = 21), and no treatment (N = 25).


RESULTS
The MMC tissue concentration in the rat model was much higher after chemoembolization than after chemoperfusion for at least 1.5 hours. The MMC serum concentration in the dogs showed a high initial peak (0.6 mg/L) after chemoperfusion, then dropped quickly to the same level seen 30 minutes after chemoembolization with 1 mg of MMC/mL of Ethibloc (0.15 mg/L). The MMC serum concentration following chemoembolization with 2 mg of MMC/mL of Ethibloc stayed higher (0.3-0.25 mg/L) for 60 minutes. The survival rates after nephrectomy were equal to those after chemoembolization (80% survival after 30 days), with poorer survival being seen after embolization (75%) and chemoperfusion (70%). In the control group, all rats were dead at the 27th day.


CONCLUSIONS
Chemoembolization produces persistently high tissue concentrations of MMC and avoids toxic peak serum levels. It improves the efficacy of organ ablative vasoocclusion in renal malignancies.
Kurzidem
M
M
Department of Urology, Klinikum Heilbronn, University of Heidelberg, Am Gesundbrunnen 20, 74074 Heilbronn, Germany.
Seidensticker
P
P
Rassweiler
J
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D003973:Diatrizoate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005227:Fatty Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000628:therapy; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023421:Models, Animal; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D012077:Renal Artery; D012517:Sarcoma, Yoshida / Q000628:therapy; D012597:Sclerosing Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015028:Zein / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D005227:Fatty Acids; D011409:Propylene Glycols; D012597:Sclerosing Solutions; D003973:Diatrizoate; D016685:Mitomycin; D015028:Zein; C020481:alcoholic prolamine solution