Document Detail


Phase I trial of oral S-1 combined with gemcitabine and cisplatin for advanced biliary tract cancer (KHBO1002).
MedLine Citation:
PMID:  22237958     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: We aimed to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the addition of S-1, an oral fluorouracil derivative, to gemcitabine and cisplatin combination therapy, which is the current standard treatment for advanced biliary tract cancer. METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The planned dosages of gemcitabine (mg/m(2))/cisplatin (mg/m(2))/S-1 (mg/m(2)/day) were as follows: level 0, 800/25/60; level 1, 1,000/25/60; and levels 2 and 3, 1,000/25/80. In each cycle, gemcitabine and cisplatin were intravenously administered on day 1 (or days 1 and 8 at level 3), and S-1 was orally administered twice daily on days 1-7 (or days 1-14 at level 3); this was repeated every 14 days (or 21 days at level 3). RESULTS: Seventeen patients were enrolled, and level 1 was chosen as the starting dose. Two of six patients developed DLTs (grade 4 neutropenia and grade 3 febrile neutropenia) at level 1, and the dose was escalated to level 2. DLTs (grade 3 rashes and grade 3 vasovagal reactions) occurred in two of six assessable patients at level 2; we then proceeded to level 3. The first three assessable patients enrolled at level 3 developed DLTs (two cases of grade 4 neutropenia, one of grade 4 leucopenia, two of grade 3 fatigue, one of grade 3 anorexia, and one of grade 3 febrile neutropenia) during their first cycle, and this dose was determined to be the MTD. Therefore, we selected level 2 as the recommended dose (RD) for a subsequent phase II study. CONCLUSIONS: We determined the RD of gemcitabine/cisplatin/S-1 combination therapy for advanced biliary tract cancer; we are proceeding to a phase II study to investigate the efficacy of this combination therapy for advanced biliary tract cancer.
Authors:
Masashi Kanai; Etsuro Hatano; Syogo Kobayashi; Yutaka Fujiwara; Daisuke Sakai; Yuzo Kodama; Tetsuo Ajiki; Hiroaki Nagano; Tatsuya Ioka
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-12
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  -     ISSN:  1432-0843     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Outpatient Oncology Unit, Kyoto University Hospital, Kyoto, Japan, kanai@kuhp.kyoto-u.ac.jp.
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