Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.
BACKGROUND
Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.


METHODS
Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.


RESULTS
The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).


CONCLUSIONS
This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.
Department of Surgery, Sahlgrenska Hospital, Göteborg, Sweden.
L
L
Hafström
B
B
Engarås
S B
SB
Holmberg
B
B
Gustavsson
P E
PE
Jönsson
P
P
Lindnér
P
P
Naredi
G
G
Tidebrant
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D003250:Constriction; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery / Q000601:surgery*; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D016019:Survival Analysis; D016896:Treatment Outcome
D000493:Allopurinol; D005472:Fluorouracil