title: Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO).
abstract: BACKGROUND
  The aim of the study was to establish the recommended dose and to evaluate the safety of gefitinib plus FUFOX regimen in irinotecan-refractory colorectal carcinoma (CRC).
  
  
  METHODS
  Patients with advanced CRC progressing on fluoropyrimidine/irinotecan-based chemotherapy and with an ECOG performance level 0-2 were enrolled. Four dose levels with sequential dose escalation of oral gefitinib and FUFOX were tested. Each cycle consisted of 5 weeks with gefitinib given daily to weekly FUFOX x4 to be repeated at day 36.
  
  
  RESULTS
  Eighteen patients were enrolled. No dose-limiting toxicity (DLT) was observed at the dose levels L1-L3. At L4 diarrhea was the major DLT requiring treatment interruption in 3 patients. Other grade 3/4 toxicities were observed with skin rash, paresthesia, anemia, and nausea/vomiting (n = 1 each). Grade 1/2 toxicities consisted of diarrhea (n = 9), mucositis (8), skin rash (10), paresthesia (10), nausea (7) as well as leukopenia (2) and fever (1). Clinical benefit was seen in 11 of 16 evaluable patients (69%): 4 patients showed partial response (25%), 7 stable disease (44%). Median time to progression was 219 days (range 50-387 days).
  
  
  CONCLUSIONS
  Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m(2) or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m(2) plus oxaliplatin has an acceptable safety profile.
authors.affiliation: Abteilung Onkologie/Hämatologie/Immunologie/Rheumatologie/Pulmologie, Südwestdeutsches Tumorzentrum -Comprehensive Cancer Center Tübingen, Eberhard-Karls-Universität Tübingen, Germany. joerg.hartmann@med.uni-tuebingen.de
authors.forename: Jorg Thomas
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: Pintoffl
authors.forename: Hendrik
authors.initials: H
authors.lastname: Kröning
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Martin
authors.initials: M
authors.lastname: Holtmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Höhler
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D000077156:Gefitinib; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008452:Maximum Allowable Concentration; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D000077156:Gefitinib; D005472:Fluorouracil; D002166:Camptothecin