Dose escalating clinical study of high dose infusional 5-fluorouracil and leukovorin (AIO regimen) plus alternate weekly administration of oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal tract

作者：Gkioulbasanis I; Souglakos J; Vardakis N; Kotsakis A; Saridaki Z; Kentepozidis N; Polyzos A; Giassas S; Ignatiadis M; Bozionelou V; Christophylakis C; Georgoulias V^*

来源：Journal of Buon, 2007, 12(2): 197-202.

• 5-fluorouracil
• gastrointestinal tumors
• irinotecan
• leukovorin
• oxaliplatin
• phase I

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of weekly high dose 5-fluorouracil (5FU) continuous infusion and leukovorin (LV) alternatively combined with oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal (GI) tract.
Patients and methods: Patients received a fixed dose of L V (500 mg/m(2)) over 2 It infusion on weeks 1 to 4 and escalated doses of: oxaliplatin (starting dose 65 mg/m(2);. 120 min i.v. infusion on weeks 1 and 3); irinotecan (starting dose 80 mg/m(2); 90 min i. v. infusion on weeks 2 and 4) and 5FU (starting dose 1500 mg/m(2); 22 h continuous i.v. infusion, on weeks 1 to 4), in cycles of 5 weeks. DLTs were evaluated during the first cycle.
Results: Twenty-eight patients were treated on 8 dose levels and all but two patients received the regimen at least as second-line treatment. The DLT level was reached at the oxaliplatin dose of 90 mg/m(2), irinotecan dose of 110 mg/m(2), LV dose of 500 mg/m(2) and 5FU dose of 1750 mg/m(2), the recommended MTDs were 85 mg/m(2) for oxaliplatin, 110 mg/m(2) for irinotecan, 1750 mg/m(2) for 5FU and 500 mg/m(2) for LV Grade 3 or 4 diarrhea and grade 3 nausea/vomiting were the dose-limiting events. Diarrhea was the most common toxicity of the regimen, occurring in 12 (42.8%) patients. Hematological toxicity was mild and there were no treatment-related deaths.
Conclusion: This weekly regimen showed a favorable toxicity profile and merits further investigation inpatients with advanced/metastatic tumors of the GI tract.

• 出版日期2007-6
• 单位中国人民解放军第四〇一医院