title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Patients received a fixed dose of LV (500 mg/m(2)) over 2 h 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 fi rst 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.
  
  
  CONCLUSIONS
  This weekly regimen showed a favorable toxicity profile and merits further investigation in patients with advanced/metastatic tumors of the GI tract.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Gkioulbasanis
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
authors.forename: N
authors.initials: N
authors.lastname: Vardakis
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.forename: Z
authors.initials: Z
authors.lastname: Saridaki
authors.forename: N
authors.initials: N
authors.lastname: Kentepozidis
authors.forename: A
authors.initials: A
authors.lastname: Polyzos
authors.forename: S
authors.initials: S
authors.lastname: Giassas
authors.forename: M
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: V
authors.initials: V
authors.lastname: Bozionelou
authors.forename: C
authors.initials: C
authors.lastname: Christophylakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin