title: Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin- refractory colorectal cancer: a phase I/II study of the Arbeitsgemeinschaft für Internistische Onkologie (AIO).
abstract: BACKGROUND
  Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer.
  
  
  METHODS
  Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/ 500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/ 80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy.
  
  
  RESULTS
  13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease.
  
  
  CONCLUSIONS
  Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRIAIO alone.
authors.affiliation: Onkologisches Zentrum, III. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Germany. ralf.hofheinz@med3.ma.uni-heidelberg.de
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicka
authors.forename: Jörg
authors.initials: J
authors.lastname: Wollert
authors.forename: Dirk
authors.initials: D
authors.lastname: Arnold
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D000077156:Gefitinib; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D000077156:Gefitinib; D005472:Fluorouracil; D002166:Camptothecin