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pubmed:abstractText |
S-1 is an oral fluorouracil anticancer drug that contains the 5-FU prodrug tegafur. Tegafur has been shown to be converted enzymatically to 5-FU to exert its antitumor effect, and this conversion is principally catalyzed by CYP2A6. Forty-six non-small-cell lung cancer patients were enrolled. The frequencies of the CYP2A6*4C, CYP2A6*7, and CYP2A6*9 alleles were 17.4, 19.6, and 15.2%, respectively. In the S-1 pharmacokinetic analysis, the area under the concentration-time curve from 0 to 10 h (AUC(0-10)) ratios of 5-FU/tegafur showed large interindividual variabilities, ranging from 5.14 to 112.6. The AUC(0-10) for tegafur was 1.5-fold higher in patients with the CYP2A6*4C allele than in patients without the CYP2A6*4C allele P < 0.05). Furthermore, patients with the CYP2A6*4C allele had a significantly lower maximum plasma concentration (102.6 +/- 32.9 ng/ml) for 5-FU than patients without the CYP2A6*4C allele (157.0 +/- 65.5 ng/ml, P < 0.05). Genotyping of CYP2A6 polymorphisms may provide vital information for effective cancer therapy using S-1.
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