ISSN:
1569-8041
Keywords:
biochemical modulation
;
colorectal cancer
;
5-fluorouracil
;
high- versus low-dose
;
L-leucovorin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: Although leucovorin (LV) + 5-fluorouracil (5-FU) isconsidered the treatment of choice for advanced colorectal cancer in mostcountries, the optimal schedule of this combination has not yet beenestablished. Low-dose LV appears to be as active as high-dose LV in thedaily-times-five regimen, but no randomized study of the levorotatorystereoisomer (6S-LV) given at two different dose levels has been published. Patients and methods: Between November 1991 and June 1994, 422patients (all with measurable disease previously untreated with chemotherapy)were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg/sqm/15 min i.v.infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10mg/sqm/i.v.) + 5-FU (doses as above), also given for 5 days every 28 days (armB). The primary endpoint of the study was the comparison of response rates(WHO criteria); the secondary endpoint was the assessment of survival andtolerability. No evaluation of the quality of life or the symptomatic effectof treatment was planned. Results: The response rate was 9.3% in arm A (95% CI:5.4–13.1), with 2 CR and 18 PR, and 10.7% in arm B (95%CI: 6.5–14.9), with 3 CR + 19 PR, without any significant difference(P = 0.78). The median time to progression was eight months in bothgroups and overall survival was 11 months, with no difference betweentreatments. Toxicity mainly consisted of gastrointestinal side effects(mucositis and diarrhoea), which were rarely severe (grade 3–4:5%–10% of patients) and similar in the two groups. Conclusions: In this large-scale multicentre trial, the low and highdoses of 6S-LV appeared to be equivalent in terms of the biochemicalmodulation of 5-FU in advanced colorectal cancer although, for several reasons(including the timing and the strict criteria of response evaluation, the highnumber of patients with unfavourable prognostic factors, themulti-institutional nature of the study, the dose and modality of 5-FUadministration), the response rate was lower than that reported in some of theother published studies. Given the considerable difference in economic costbetween the two dosages, the use of high-dose 6S-LV in the daily-times-fiveregimen is not recommended in clinical practice.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008200713533
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