Abstract | BACKGROUND: Although leucovorin (LV) + 5-fluorouracil (5-FU) is considered the treatment of choice for advanced colorectal cancer in most countries, the optimal schedule of this combination has not yet been established. Low-dose LV appears to be as active as high-dose LV in the daily-times-five regimen, but no randomized study of the levorotatory stereoisomer (6S-LV) given at two different dose levels has been published. PATIENTS AND METHODS: Between November 1991 and June 1994, 422 patients (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 (10 mg/sqm/i.v./5-FU (doses as above), also given for 5 days every 28 days (arm B). The primary endpoint of the study was the comparison of response rates (WHO criteria): the secondary endpoint was the assessment of survival and tolerability. No evaluation of the quality of life or the symptomatic effect of 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 both groups and overall survival was 11 months, with no difference between treatments. 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 high doses of 6S-LV appeared to be equivalent in terms of the biochemical modulation of 5-FU in advanced colorectal cancer although, for several reasons (including the timing and the strict criteria of response evaluation, the high number of patients with unfavourable prognostic factors, the multi-institutional nature of the study, the dose and modality of 5-FU administration), the response rate was lower than that reported in some of the other published studies. Given the considerable difference in economic cost between the two dosages, the use of high-dose 6S-LV in the daily-times-five regimen is not recommended in clinical practice.
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Authors | R Labianca, S Cascinu, L Frontini, S Barni, G Fiorentini, G Comella, A Zaniboni, O Gottardi, E Arnoldi, C Oliani, M Duro, G Pavanato, G Martignoni, A Raina, E Piazza, G Dallavalle, R Valsecchi, G Pancera, G Luporini |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 8
Issue 2
Pg. 169-74
(Feb 1997)
ISSN: 0923-7534 [Print] England |
PMID | 9093726
(Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Colorectal Neoplasms
(drug therapy)
- Drug Administration Schedule
- Female
- Fluorouracil
(administration & dosage, adverse effects)
- Humans
- Leucovorin
(administration & dosage)
- Male
- Middle Aged
- Treatment Outcome
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