Dose-effect relationship of bolus 5-fluorouracil in the treatment of advanced colorectal cancer.
Acta Oncol
; 41(6): 525-31, 2002.
Article
em En
| MEDLINE
| ID: mdl-12546525
ABSTRACT
The effect of different dose intensities of 5-fluorouracil (5-FU) in advanced colorectal cancer was investigated. A total of 312 patients were randomized to receive 400 mg/m2 (group A), 500 mg/m2 (group B) or 600 mg/m2 (group C) of 5-FU with leucovorin 60 mg/m2 on two consecutive days every second week. Treatment continued to progression. Pharmacokinetic analyses with calculation of the area under the concentration (AUC) were performed in 91 patients. The primary endpoint was survival, and secondary endpoints were time to disease progression, toxicity and, if the disease was measurable, tumour response. The study was well balanced in the three groups with respect to a number of patient characteristics. Crude survival as estimated by Kaplan-Meier plots was not statistically significantly different (p = 0.07) but tended to show the best results in the intermediate dose group (median survival 10, 12.5 and 10 months, respectively). Analyses of time to progression or death showed significant differences among the three groups (p = 0.02) with the longest progression-free interval in the intermediate group receiving 500 mg/m2. The objective response rates were 23%, 39% and 28%, respectively (p = 0.02). The actual/projected dose intensity (mg/m2/week) was 92%, 92% and 84%, respectively. AUC did not correlate with response or survival. The frequency of severe side effects in group C was significantly higher than that of groups A and B. The study indicated that an increase from 800 to 1000 mg/m2 of bolus 5-FU fortnightly improved the treatment results but a further increase only worsened the toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Fluoruracila
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Acta Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Dinamarca