Search

The use of bolus 5-fluorouracil (5-FU) as a short-term infusion over 10-30 min is increasing at the cost of a push injection, mainly due to practical advantages. Since even a short prolongation of the administration time results in lower 5-FU peak and area under the curve (AUC) levels, there might be a risk of decreased efficacy. The aim of this study was to compare a rapid intravenous (i.v.) 5-FU injection and a short-term 5-FU infusion with respect to objective responses and toxicity in patients with advanced colorectal cancer. 203 patients with measurable advanced colorectal cancer were randomised to bolus 5-FU either as an injection for 2-4 min or as a short-term infusion lasting 10-20 min. In both groups, the 5-FU dose was 500 mg/m2 and leucovorin 60 mg/m2 was given 40 min after the start of 5-FU. Treatment was given on two successive days every other week until progression. Objective tumour regression was seen in 27/100 (27%) in the injection group and in 13/103 (13%) in the infusion group (P = 0.02). Severe toxicity was rare and did not differ significantly between the groups. Progression-free survival tended to be longer in the injection group (P = 0.07), but overall survival did not differ between the groups. Bolus 5-FU should be administered as a rapid i.v. injection rather than as a short-term infusion, since the former rate of administration results in a higher response rate without being significantly more toxic.

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

Carl J, Brunsgaard N, Kjaer M, Norgaard-Pedersen B. Estimated treatment responses in metastatic colorectal carcinoma based on longitudinal carcinoembryonic antigen series. Scand J Clin Lab Invest 1993; 53: 829-834.Patients presenting with advanced or metastatic colorectal carcinoma were randomized to treatment with either 5-Fluoro-Uracil + leucovorin or 5-Fluoro-Uracil + interferon α-2-a. Longitudinal series of Carcino-embryonic-antigen were obtained and analyzed with a dynamic model in seven of 16 patients had CEA levels above lOngml−1. Clinical evaluation based on X-ray, ultrasound and CT-scans showed a partial response to the given treatment in three of the seven patients. The dynamic model consistinly estimated the maximal accumulated cell kill (approximately three logs) in the patients experiencing a clinical response. The remaining four patients with CEA levels above lOngml−1 showed some reduction in CEA as a consequence of the treatment cycles, although no clinical response could be established. No...

The use of bolus 5-fluorouracil (5-FU) as a short-term infusion over 10-30 min is increasing at the cost of a push injection, mainly due to practical advantages. Since even a short prolongation of the administration time results in lower 5-FU peak and area under the curve (AUC) levels, there might be a risk of decreased efficacy. The aim of this study was to compare a rapid intravenous (i.v.) 5-FU injection and a short-term 5-FU infusion with respect to objective responses and toxicity in patients with advanced colorectal cancer. 203 patients with measurable advanced colorectal cancer were randomised to bolus 5-FU either as an injection for 2-4 min or as a short-term infusion lasting 10-20 min. In both groups, the 5-FU dose was 500 mg/m2 and leucovorin 60 mg/m2 was given 40 min after the start of 5-FU. Treatment was given on two successive days every other week until progression. Objective tumour regression was seen in 27/100 (27%) in the injection group and in 13/103 (13%) in the infusion group (P = 0.02). Severe toxicity was rare and did not differ significantly between the groups. Progression-free survival tended to be longer in the injection group (P = 0.07), but overall survival did not differ between the groups. Bolus 5-FU should be administered as a rapid i.v. injection rather than as a short-term infusion, since the former rate of administration results in a higher response rate without being significantly more toxic.