Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.
OBJECTIVE
We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC.


METHODS
Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks.


RESULTS
Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases.


CONCLUSIONS
IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.
Nagai
Hidenari
H
Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo 143-8541, Japan. hidenari@aol.com
Matsui
Teppei
T
Kanayama
Masahiro
M
Momiyama
Kouichi
K
Shizawa
Kazue
K
Wakui
Noritaka
N
Shinohara
Mie
M
Watanabe
Manabu
M
Iida
Kazunari
K
Ishii
Koji
K
Igarashi
Yoshinori
Y
Sumino
Yasukiyo
Y
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001201:Ascites / Q000139:chemically induced / Q000209:etiology; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D024141:Collagen Type IV / Q000097:blood; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007261:Infusions, Intra-Arterial / Q000009:adverse effects*; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D000637:Transaminases / Q000097:blood
D024141:Collagen Type IV; D010446:Peptide Fragments; D011347:Procollagen; D012709:Serum Albumin; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid; D000637:Transaminases; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil