Cited 47 times in
Phase I and Pharmacokinetic study of the oral fluoropyrimidine S-1 on a Once-Daily-for-28-day schedule in patients with advanced malignancies
DC Field | Value | Language |
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dc.contributor.author | 라선영 | - |
dc.date.accessioned | 2015-07-14T17:15:34Z | - |
dc.date.available | 2015-07-14T17:15:34Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/112525 | - |
dc.description.abstract | PURPOSE: The oral fluoropyrimidine S-1, which consists of a mixture of a 5-fluorouracil (5-FU) prodrug (tegafur), a dihydropyrimidine dehydrogenase inhibitor [5-chloro-2,4-dihydroxypyrimidine (CDHP)], and an inhibitor of orotate phosphoribosyltransferase [potassium oxonate (oxonic acid)], was developed to increase the feasibility and therapeutic index of 5-FU administered orally. The principal objective of this study was to assess the feasibility of administering S-1 on a once-daily-for-28-day schedule every 5 weeks, determine the maximum tolerated dose, characterize the pharmacokinetics of S-1, and seek evidence of anticancer activity. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were treated with escalating doses of S-1 on a once-daily oral schedule for 28 days every 5 weeks. The maximum tolerated dose was defined as the highest dose in which fewer than two of the first six new patients experienced dose-limiting toxicity. The pharmacokinetic profiles of the tegafur, CDHP, and oxonic acid constituents were characterized. RESULTS: Twenty patients were treated with 72 courses of S-1 at three dose levels ranging from 50 to 70 mg/m(2)/day. Diarrhea, which was often associated with abdominal discomfort and cramping, was the principal dose-limiting toxicity of S-1 on this protracted schedule. Nausea, vomiting, mucositis, fatigue, and cutaneous effects were also observed but were rarely severe. Myelosuppression was modest and uncommon. A partial response and a 49% reduction in tumor size were observed in patients with fluoropyrimidine- and irinotecan-resistant colorectal carcinoma. The pharmacokinetic data suggested potent inhibition of 5-FU clearance by CHDP, with resultant 5-FU exposure at least 10-fold higher than that reported from equitoxic doses of tegafur modulated by uracil in the oral fluoropyrimidine UFT. CONCLUSIONS: The recommended dose for Phase II studies of S-1 administered once daily for 28 consecutive days every 5 weeks is 50 mg/m(2)/day. The pharmacokinetic data indicate substantial modulation of 5-FU clearance by CDHP. Based on these pharmacokinetic data, the predictable toxicity profile of S-1, and the low incidence of severe adverse effects at the recommended Phase II dose, evaluations of S-1 on this schedule are warranted in malignancies that are sensitive to the fluoropyrimidines. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 4913~4921 | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Phase I and Pharmacokinetic study of the oral fluoropyrimidine S-1 on a Once-Daily-for-28-day schedule in patients with advanced malignancies | - |
dc.type | Article | - |
dc.contributor.college | Researcher Institutes (부설 연구소) | - |
dc.contributor.department | Cancer Metastasis Research Center (암전이연구센터) | - |
dc.contributor.googleauthor | Quincy Siu-Chung Chu | - |
dc.contributor.googleauthor | Lisa A. Hammond | - |
dc.contributor.googleauthor | Eric K. Rowinsky | - |
dc.contributor.googleauthor | Arthur P. DeCillis | - |
dc.contributor.googleauthor | Bharat Damle | - |
dc.contributor.googleauthor | Stephen P. Letrent | - |
dc.contributor.googleauthor | Brian Roedig | - |
dc.contributor.googleauthor | Kathleen Molpus | - |
dc.contributor.googleauthor | Louis Denis | - |
dc.contributor.googleauthor | Sun-Young Rha | - |
dc.contributor.googleauthor | Leonel Ochoa | - |
dc.contributor.googleauthor | Garry Schwartz | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-04-0469 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.relation.journalcode | J00564 | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 10 | - |
dc.citation.number | 15 | - |
dc.citation.startPage | 4913 | - |
dc.citation.endPage | 4921 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.10(15) : 4913-4921, 2004 | - |
dc.identifier.rimsid | 57724 | - |
dc.type.rims | ART | - |
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