Twelve weeks of protracted venous infusion of fluorouracil (5-FU) is as effective as 6 months of bolus 5-FU and folinic acid as adjuvant treatment in colorectal cancer.
We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of 5-fluorouracil (5-FU) delivered by protracted intravenous infusion (PVI 5-FU) against the standard bolus regimen of 5-FU and folinic acid (5-FU/FA) given for 6 months as adjuvant treatment in colorectal cancer. A total of 716 patients with curatively resected Dukes' B or C colorectal cancer were randomised to 5-FU/FA (5-FU 425 mg m(-2) i.v. and FA 20 mg m(-2) i.v. bolus days 1-5 every 28 days for 6 months) or to PVI 5-FU alone (300 mg m(-2) day for 12 weeks). With a median follow-up of 19.8 months, 133 relapses and 77 deaths have been observed. Overall survival did not differ significantly (log rank P=0.764) between patients receiving 5-FU/FA and PVI 5-FU (3-year survival 83.2 vs 87.9%, respectively). Patients in the 5-FU/FA group had significantly worse relapse-free survival (RFS, log rank P=0.023) compared to those receiving PVI 5-FU (3-year RFS, 68.6 vs 80%, respectively). Grades 3-4 neutropenia, diarrhoea, stomatitis and severe alopecia were significantly less (P<0.0001) and global quality of life scores significantly better (P&<0.001) for patients in the PVI 5-FU treatment arm. In conclusion, infused 5-FU given over 12 weeks resulted in similar survival to bolus 5-FU and FA over a 6 month period, but with significantly less toxicity.
Saini
A
A
Royal Marsden Hospital, London and Surrey, UK.
Norman
A R
AR
Cunningham
D
D
Chau
I
I
Hill
M
M
Tait
D
D
Hickish
T
T
Iveson
T
T
Lofts
F
F
Jodrell
D
D
Ross
P J
PJ
Oates
J
J
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011788:Quality of Life
D000970:Antineoplastic Agents; D002955:Leucovorin; D005472:Fluorouracil