TY - JOUR
T1 - High-versus low-dose levo-leucovorin as a modulator of 5-fluorouracil in advanced colorectal cancer
T2 - A 'GISCAD' phase III study
AU - Labianca, R.
AU - Cascinu, S.
AU - Frontini, L.
AU - Barni, S.
AU - Fiorentini, G.
AU - Comella, G.
AU - Zaniboni, A.
AU - Gottardi, O.
AU - Arnoldi, E.
AU - Oliani, C.
AU - Duro, M.
AU - Pavanato, G.
AU - Martignoni, G.
AU - Raina, A.
AU - Piazza, E.
AU - Dallavalle, G.
AU - Valsecchi, R.
AU - Pancera, G.
AU - Luporini, G.
PY - 1997/2
Y1 - 1997/2
N2 - 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.
AB - 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.
KW - 5-fluorouracil
KW - biochemical modulation
KW - colorectal cancer
KW - high-versus low-dose
KW - L-leucovorin
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U2 - 10.1023/A:1008200713533
DO - 10.1023/A:1008200713533
M3 - Article
C2 - 9093726
AN - SCOPUS:0013405202
VL - 8
SP - 169
EP - 174
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 2
ER -