Table 1 Prior studies of circadian variability in 5-fluorouracil plasma levels during CVI
From: Circadian variation in plasma 5-fluorouracil concentrations during a 24 hour constant-rate infusion
Reference | Pts | 5-FU dose (mg/m2/d) | Sampling (hours) | Data analysis | Peak time | Trough time | Estimated [5-FU] change (peak to trough) |
|---|---|---|---|---|---|---|---|
Petit [6] | 7 | 450-966 | Q3 | ANOVA of mean transformed [5-FU] by time (% change from pt mean) | 1:00 | 13:00 | −43% (2× amplitude from cosinor analysis) |
Harris [4] | 7 | 300 | Q3 | Cosinor analysis of transformed [5-FU] (% change from pt mean) | 11:00 | 23:00 | −80% (mean of individual patient peaks and troughs) |
Sparano [7] | 15 | 150-300 | Q1-16 | Cosinor analysis of transformed [5-FU] (% change from pt mean) | 8:00 | 20:00 | −2.5 standard deviations from individual’s mean [5-FU] (at individual’s peak and trough) |
Metzger [8] | 4 | 600 | Q6 | ANOVA of mean [5-FU] by time | 4:00 | 13:00 | −88% (mean [5-FU] at the population’s peak and trough) |
Van Kuilenburg [9] | 5 | 300-450 | Q4 | Not stated | No circadian variation observed | ||
Strocchi [10] | 9 | 600 | Q3 | Not stated | 3 of 9 pts had “marked circadian variation” but peak was variable | ||
Takimoto [11] | 14 | 1758 | Q3 | ANOVA of mean [5-FU] by time (Kruskal-Wallis test) | No consistent circadian variation observed; 5 Fu concentrations within individuals varied 1.7 fold | ||
Kuwahara [12] | 35 | 400-550 | Q12 | Comparison of two timepoints | Higher concentrations observed at 17:00 and lower at 5:00. Difference observed only at lower dosage. | ||