Chemoembolization of rat liver metastasis with irinotecan and quantification of tumor cell reduction.
OBJECTIVE
Hematogenic metastasis of patients with colorectal cancer most frequently effects the liver; the prognosis of affected patients is dramatically worsened by the presence of this lesion. The aim of this study was to evaluate the effect of hepatic arterial chemoembolization (HACE) with irinotecan versus 5-fluorouracil as a standard agent in a rat liver metastasis model.


METHODS
Diffuse liver metastasis was induced by injecting 4 x 10(6) CC531-lac-Z rat colorectal carcinoma cells into the portal vein of male Wag/Rij rats. Irinotecan (10 mg/kg, 30 mg/kg, and 60 mg/kg) and 5-fluorouracil (40 mg/kg, 60 mg/kg, and 90 mg/kg) were administered concomitantly with degradable starch microspheres (30 mg/kg) for temporary embolization. The tumor cell load was determined quantitatively using a chemoluminescence assay.


RESULTS
HACE with irinotecan induced a complete remission in 44% of the animals and the highest dose reduced the mean tumor cell load by 66% (P < 0.001). In contrast, the highest dose of 5-FU caused a reduction of only 18% (P = 0.026) and altogether 23% complete remissions were observed in response to 5-FU. The sensitivity of CC531-lac-Z cells versus irinotecan (IC50 32 pM after 72 h) and 5-FU (IC50 80 microM) mirrored the effects observed in vivo on a qualitative basis.


CONCLUSIONS
In conclusion, the effect of HACE with irinotecan surpassed that of HACE with 5-FU and prompts further investigation in clinical trials.
Saenger
Jan
J
Unit of Toxicology and Chemotherapy, German Cancer Research Center, Im Neuenheimer Feld 120, 69120, Heidelberg.
Leible
Maike
M
Seelig
Matthias H
MH
Berger
Martin R
MR
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003110:Colonic Neoplasms / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D000077146:Irinotecan; D008163:Luminescent Measurements; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin