Randomized trial of intraportal and/or systemic adjuvant chemotherapy in patients with colon carcinoma.
BACKGROUND
5-fluorouracil-based adjuvant chemotherapy after surgical resection of colon cancer is standard treatment. However, the choice of best delivery route--that is, systemic (i.e., intravenous or oral) or regional (i.e., intraportal, intraperitoneal, or hepatic arterial infusion)--has been controversial. In a randomized clinical trial of patients with colon cancer, we compared the benefits of chemotherapy delivered by these routes individually or in combination.


METHODS
From April 2, 1992, through April 30, 1998, 1084 eligible patients with Dukes' stage B or C colon carcinoma were randomly assigned: 369 patients to the IP regimen (continuous portal vein infusion of 5-fluorouracil at 500 mg/m2 of body surface daily and heparin at 5000 IU daily for 7 consecutive days, beginning on the day of surgery), 358 patients to the SY regimen (six 28-day courses of systemic leucovorin at 100 mg/m2 daily on days 1 through 5 followed by systemic bolus 5-fluorouracil at 370 mg/m2 daily on days 1 through 5, with treatment initiated 15-35 days after surgery), and 357 patients to the IP+SY regimen (the IP regimen followed by the SY regimen, with the same scheduling). Primary survival was analyzed with the log-rank statistic and a Cox multivariable regression model. All statistical tests were two sided.


RESULTS
At a median follow-up time of 99 months, 389 events (recurrences, second malignancies, or deaths) had occurred, and 361 patients died. Sites of first recurrences were similar among the three arms. At 5 years, overall and event-free survival rates were similar among those on the IP (74% and 68%, respectively), SY (78% and 71%), and IP+SY (73% and 67%) regimens. When compared with the group on the SY regimen, the risk for death associated with the IP regimen (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.82 to 1.36) was similar to that associated with the IP+SY regimen (HR = 1.12, 95% CI = 0.78 to 1.45) (P =.69), as were the risks for first event (HR = 1.07, 95% CI = 0.84 to 1.37 and HR = 1.10, 95% CI = 0.86 to 1.41, respectively) (P=.74).


CONCLUSIONS
Overall and event-free survival rates were similar in all three arms. The combined regimen was no better than either single regimen alone.
Labianca
Roberto
R
Unità Operativa di Oncologia Medica, Ospedali Riuniti, Bergamo, Italy (RL).
Fossati
Roldano
R
Zaniboni
Alberto
A
Torri
Valter
V
Marsoni
Silvia
S
Nitti
Donato
D
Boffi
Lamberto
L
Scatizzi
Marco
M
Tardio
Berardino
B
Mastrodonato
Nicola
N
Banducci
Stefano
S
Consani
Giampiero
G
Pancera
Gianfranco
G
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007558:Italy; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011169:Portal Vein; D011379:Prognosis; D012107:Research Design; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil