A COMPARATIVE-STUDY WITH 2 ADMINISTRATION SCHEDULES OF LEUCOVORIN AND5-FLUOROURACIL IN ADVANCED COLORECTAL-CANCER

One hundred and seven previously untreated patients with measurable me tastatic colorectal cancer who were treated with 5-fluorouracil (5FU) and leucovorin (LV) in two different maximum doses and schedules were retrospectively analyzed. Group A, 52 pts, was treated with LV 200 mg/ m(2)/D IV push, followed by 5FU 700 mg/m(2)/D IV 1 h infusion for 5 D. Cycle was repeated every 21 D. Group B, 55 pts, was treated with LV 5 00 mg/m(2)/D in a 2 h infusion and 5FU 600 mg/m(2)/D IV bolus at mid-t ime of LV infusion, repeated every week for 6 wk followed by 2-wk rest period. There was no difference in response (A 8%, B 11%). Median sur vival for A was 37 (2-131) wk, B was 59 (1-112) wk (P = 0.021), time t o progression for A was 20 (0-131) wk, B 30 (0-102) wk (P = 0.021). Ad ministered mean dose intensity of LV was 350.8 mg/m(2)/wk in group A a nd 405.0 mg/m(2)/wk in group B without any significant difference; tha t of 5FU was significantly higher in group A as compared to group B (1 205.3 vs 468.9 mg/m(2)/wk, respectively) (p < 0.0001). This difference was a consequence of the planned dose intensity for this drug in the two treatment regimens. Toxicity was more frequent and intense in grou p A for mucositis (P < 0.001), fatigue (P < 0.01), and neurotoxicity ( P < 0.05), and in group B for neutropenia (P < 0.001) and nausea-vomit ing (P < 0.001). There were one and four iatrogenic deaths in group A and B patients, respectively (NS). Although this study was not prospec tive and randomized, we can conclude that toxicity was significantly d ifferent in the two groups, with a prevalence of mucositis in group A and neutropenia in group B and a higher number of iatrogenic deaths in the latter group. Response rates were the same for the two groups alt hough survival and time to progression were significantly increased fo r group B patients.