© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 497-505, Copyright © 1997 by Oxford University Press
BACKGROUND: Systemic delivery of cytotoxic drugs yields relatively low
doses in the liver, a major site of recurrence for colorectal cancer.
Giving chemotherapy by means of continuous portal vein infusion (PVI) into
the liver during the immediate postoperative period may improve therapeutic
efficacy. PURPOSE: We undertook a meta-analysis to assess the effects on
recurrence and survival of administering fluorouracil (5- FU)-based
chemotherapy by PVI after colorectal cancer surgery. METHODS: Data on
mortality and recurrence were sought for all patients enrolled in
randomized trials initiated before 1987 in which a few days (range, 5-7
days) of continuous postoperative PVI of cytotoxic drugs was compared with
no further treatment. Data from 10 trials (a promising initial study and
nine hypothesis-testing trials) involving about 4000 patients were
available for analysis. The main cytotoxic drug in each trial was 5-FU
(given with heparin); however, mitomycin C was co- administered in two of
the trials. Four trials included an additional control group of patients
treated with continuous noncytotoxic PVI of either heparin or urokinase
alone; one trial included a second control group of patients treated with
continuous systemic infusion of 5-FU. Reported P values are two-sided.
RESULTS: Among the 3499 patients randomly assigned to receive either
cytotoxic PVI or no further treatment, 1557 deaths are known to have
occurred. Survival with and without PVI appeared to be the same for the
first 2 years; thereafter, it diverged significantly, with the absolute
survival difference (i.e., improvement) associated with PVI at 5 years
being 4.7 % (standard deviation [SD] = 1.2 %) (P = .006). When just the
nine hypothesis- testing trials were considered, the absolute survival
difference was 3.6% (SD = 1.2%) (P = .04). If, ignoring any potential for
bias in stage assignment, attention was restricted to patients with Dukes'
stage A, B, or C disease (88.3% of the total), the absolute effect on 5-
year survival for all 10 trials increased to 6.0% (SD = 1.8%) (P = .001);
this estimate remained statistically significant when the initial study was
excluded (absolute survival difference = 4.8%; SD = 1.8%; P = .01). In
contrast to the highly significant reduction in liver metastases seen in
the initial study (79% reduction; SD = 15%; P = .00000007), the reduction
found in the nine hypothesis-testing trials was not significant (14%
reduction; SD = 10%; P = .2). In the trials with additional control groups,
survival appeared to be better with cytotoxic PVI than with noncytotoxic
PVI or with systemic cytotoxic drug infusion. CONCLUSIONS: PVI of 5-FU
(with or without other cytotoxic drugs) for about 1 week after surgery in
patients with colorectal cancer may produce an absolute improvement in
5-year survival of a few percent. Although encouraging, this finding is not
statistically secure, and additional evidence from randomized trials
involving several thousand more patients is needed.
REVIEWS
Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies. Liver Infusion Meta-analysis Group
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