Bimonthly high dose leucovorin and 5-fluorouracil 48-hour continuous infusion in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

BACKGROUND

It has been suggested that there is a relationship between 5-fluorouracil (5-FU) dose levels and response rates. A bimonthly 2-day regimen of leucovorin (LV) and 5-FU bolus plus infusion has been found to be superior to a monthly 5-FU bolus with low dose LV. Based on these reports, a first-line Phase II study was performed in 101 patients with advanced colorectal carcinoma who were given a bimonthly combination of high dose LV and a high dose 48-hour infusion of 5-FU.

METHODS

The selected regimen included a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. Evaluation was performed every six cycles. This study reports the treatment of 101 patients with measurable disease.

RESULTS

World Health Organization toxicity Grade 3-4 occurred in 15% of patients, nausea in 2%, diarrhea in 5.1%, mucositis in 4%, neutropenia in 4% (Grade 4: 2%), hand-foot syndrome in 2%, alopecia in 4%, and encephalopathy in 1%. The overall response rate was 33.7%. Five patients had a complete response (5%), and 29 had a partial response (28.7%). In 45 patients disease was stable (44.6%), and in 19 patients there was disease progression (18.8%). Three patients (3%) could not be evaluated. The median progression free survival was 8 months and median survival was 18 months.

CONCLUSIONS

In the current study, bimonthly high dose LV and a high dose 48-hour infusion of 5-FU had activity in patients with advanced colorectal carcinoma. Toxicity is notably low, and the regimen is suitable for use in combination with other drugs.