Can the 2-(13)C-uracil breath test be used to predict the effect of the antitumor drug S-1?
OBJECTIVE
S-1 is an oral anticancer drug containing tegafur (FT), a pro-drug of fluorouracil, combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), at a molar ratio of 1:0.4:1. CYP2A6 genetic polymorphism and dihydropyrimidine dehydrogenase (DPD) inhibition are important for the antitumor effect of S-1. Exploiting the usefulness of the 2-(13)C-uracil breath test (UrBT) as an indicator of DPD activity, we examined whether the results of CYP2A6 genetic polymorphism analysis and UrBT could be used to predict the antitumor effect of S-1.


METHODS
Thirty-four patients with advanced or recurrent cancer (15, 16 and 3 with gastric, colorectal and pancreatic cancer, respectively) were orally administered 40 mg/m(2) S-1 twice daily in the morning and evening. Eighteen patients with a complete response (CR)/partial response (PR) (2 with CR, 16 with PR) and 16 with progressive disease (PD) were compared with respect to CYP2A6 genetic polymorphisms (1- vs. 2-allele mutation), UrBT results, and plasma FT and 5-fluorouracil levels at 3 h after S-1 ingestion in the morning.


RESULTS
On multivariate analysis between the CR/PR and PD groups, only the UrBT results was an independent factor of CR/PR to S-1 (95% CI 1.02-1.10).


CONCLUSIONS
These results suggest that the anticancer effect of S-1 can be predicted by performing UrBT 3 h after the initial oral S-1 administration.
Ishii
Yukimoto
Y
Department of Surgery, Nerima Hikarigaoka Hospital, Nihon University School of Medicine, 2-11-1 Hikarigaoka, Nerima-ku, Tokyo, 179-0072, Japan. yishii@med.nihon-u.ac.jp
Suzuki
Shigeru
S
Takahashi
Yasuo
Y
Takayama
Tadatoshi
T
Asai
Satoshi
S
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001944:Breath Tests; D002851:Chromatography, High Pressure Liquid; D065637:Cytochrome P-450 CYP2A6; D004338:Drug Combinations; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010094:Oxonic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D019275:Radiopharmaceuticals; D005641:Tegafur / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014498:Uracil
D004338:Drug Combinations; D019275:Radiopharmaceuticals; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6