BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil UFT], tegafur + gimeracil + osteracil [S-1 (TS-1)]) relative to DPD activity, with other fluoropyrimidines as controls. METHODS: The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancer patients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients. RESULTS: In patients with low DPD activity (under 40 U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40 U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (16), and progressive disease (PD) in the rest. UFF induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6). CONCLUSION: It is recommended to use S-1 rather than UFF in patients with high DPD activity. Measurement of DPD was useful in drug selection.
BACKGROUND:Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil UFT], tegafur + gimeracil + osteracil [S-1 (TS-1)]) relative to DPD activity, with other fluoropyrimidines as controls. METHODS: The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancerpatients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients. RESULTS: In patients with low DPD activity (under 40 U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40 U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (16), and progressive disease (PD) in the rest. UFF induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6). CONCLUSION: It is recommended to use S-1 rather than UFF in patients with high DPD activity. Measurement of DPD was useful in drug selection.
Authors: S Saji; K Aiba; H Araki; K Sasaki; T Shirasaka; M Sowa; M Tanaka; Y Chung; T Toge; K Hirata; K Yasumoto; S Yamamitsu; H Wada Journal: Gan To Kagaku Ryoho Date: 1997-10
Authors: S Ohwada; T Ogawa; M Izumi; T Inoue; O Teshigawara; T Ikeya; T Kusaba; T Roppongi; Y Iino; Y Morishita Journal: Anticancer Res Date: 1997 May-Jun Impact factor: 2.480
Authors: T Shirasaka; Y Shimamato; H Ohshimo; M Yamaguchi; T Kato; K Yonekura; M Fukushima Journal: Anticancer Drugs Date: 1996-07 Impact factor: 2.248
Authors: D Machover; E Goldschmidt; P Chollet; G Metzger; J Zittoun; J Marquet; J M Vandenbulcke; J L Misset; L Schwarzenberg; J B Fourtillan Journal: J Clin Oncol Date: 1986-05 Impact factor: 44.544