Phase I dose escalation study of oxaliplatin combined with oral tegafur-uracil and leucovorin in patients with advanced gastric cancer.
Our aim was to determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose of oxaliplatin combined with oral tegafur-uracil and leucovorin. Twenty-eight chemo-naive patients with advanced gastric cancer were enrolled. Oxaliplatin (55, 70, 85, 100 and 115 mg/m2) was given as a 2-h infusion on days 1 and 15. Oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) were given 3 times a day from days 1 to 21 (28-day cycle). DLTs were defined as grade IV hematologic toxicity or grade III non-hematologic toxicity. The MTD for oxaliplatin was 100 mg/m2. The most common DLT was diarrhea. Major grade III/IV toxicities included vomiting, diarrhea, renal dysfunction, leukopenia and thrombocytopenia. There were two treatment-related deaths. Intent-to-treat response was graded as partial response in 13 patients (46.4%; 95% confidence interval 26.74-66.12%), stable disease in nine and disease progression in five. As of June 2004, 17 patients had died. The median time to treatment failure, time to progression and overall survival were 124, 308 and 434 days, respectively. The recommended dose for the phase II study is oxaliplatin 100 mg/m2 biweekly with oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) 3 times a day for 21 days.
Chen
Jen-Shi
JS
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. js1101@adm.cgmh.org.tw
Huang
Jen-Seng
JS
Yang
Tsai-Shen
TS
Lin
Yung-Chang
YC
Wang
Hung-Ming
HM
Liau
Chi-Ting
CT
Rau
Kun-Ming
KM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin