Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials.
BACKGROUND
The goal of the current study was use metaanalysis to evaluate the effect of postoperative adjuvant chemotherapy after resection of hepatocellular carcinoma (HCC), especially in cirrhotic patients.


METHODS
One hundred-eight patients with radical resection of HCC were included in 1 of 3 prospective randomized control studies that used different postoperative chemotherapy protocols. Fifty-one patients underwent resection alone, and 57 patients received postoperative adjuvant chemotherapy. The first protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after surgery followed by oral tegafur (300 mg/day) for 1 year. The second protocol was intraarterial epirubicin (40 mg/m(2)) at 1 month after resection followed by intravenous epirubicin (40 mg/m(2)) every 3 months for 2 years. Additionally, carmofur 300 mg/day was administered for 2 years. The third protocol was intravenous epirubicin (40 mg/m(2)) every 2 months starting 1 month after surgery for 1 year.


RESULTS
There were no significant differences in clinicopathologic background in each of the three protocols between the groups with and without chemotherapy. Postoperative chemotherapy using the current protocols failed to improve patient outcome in all patients and failed to improve disease-free and overall survival in any patients who were included in individual protocols. In patients with cirrhosis, postoperative chemotherapy was associated with significantly worse disease-free (P = 0.0376) and overall survival rates (P = 0.0077).


CONCLUSIONS
The current study indicated that cancer recurrence in the remnant liver is enhanced and the long-term outcome is deteriorated by postoperative chemotherapy after resection of HCC in cirrhotic patients.
Ono
T
T
Second Department of Surgery, Shimane Medical University, Izumo, Japan. nigeka50@shimane-med.ac.jp
Yamanoi
A
A
Nazmy El Assal
O
O
Kohno
H
H
Nagasue
N
N
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006498:Hepatectomy; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000401:mortality* / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005641:Tegafur; D015251:Epirubicin; C017367:carmofur; D005472:Fluorouracil