Randomized trial comparing weekly bolus 5-fluorouracil plus leucovorin versus monthly 5-day 5-fluorouracil plus leucovorin in metastatic colorectal cancer

Background/Aims: The purpose of this study was to compare the efficacy and toxicity profiles of weekly intravenous (i.v.) bolus injection of 5-fluorou racil plus low-dose leucovorin with the Mayo Clinics' monthly 5-day schedul e of 5-fluorouracil and leucovorin in the treatment of metastatic colorecta l cancer. Methodology: A total of 96 patients with previously untreated metastatic co lorectal cancer were randomized to receive either a weekly i.v, bolus injec tion of 5-fluorouracil 400mg/m(2) plus leucovorin 20mg/m(2) (weekly arm), o r i.v. bolus injection of 5-fluorouracil 425mg/m(2) plus leucovorin 20mg/m( 2) for 5 consecutive days every 4 or 5 weeks (monthly arm). Therapy was con tinued until disease progression or unacceptable toxicity appeared. In the presence of disease progression, the study regimen was stopped and second-l ine treatment was instituted after the patient was discontinued from this s tudy. Results: There was no significant difference of response rates between both regimens. The response rate were 14.3% in the weekly arm (2 CR and 5 PR, 9 5% CI: 2.6-25.2%) and 10.6% in the monthly arm (1 CR and 4 PR; 95% CI: 6.5- 32.3%), respectively (P=0.8957). The survival times were also similar betwe en the two (P=0.4207, log-rank test). The median survival were 15.8 months in the monthly arm and 18.4 months in the weekly arm. Hematologic toxicity was minimal in both arms. However, the monthly arm produced a higher toxici ty in severe (grade 3-4) diarrhea (14.9% vs. 2%; P=0.029) and stomatitis (8 .5% vs. 0; P=0.054). Conclusions: Weekly bolus injection of 5-fluorouracil and low-dose leucovor in achieved a similar response rate and survival as compared with the Mayo Clinics' monthly 5-day schedule, but severe toxicity was less commonly seen using the weekly regimen. As current chemotherapeutic treatment for metast atic colorectal cancer is largely palliative rather than curative, the week ly bolus regimen may be a more favorable approach in managing metastatic co lorectal cancer.