title: A phase II study of gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin in previously untreated patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  We investigated the gefitinib, 5-fluorouracil (5-FU), leucovorin and oxaliplatin (IFOX) regimen as first-line therapy in patients with metastatic colorectal cancer.
  
  
  METHODS
  Eligible patients had stage IV colorectal adenocarcinoma, and had not received prior chemotherapy for metastatic disease. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin, leucovorin, and 5-FU (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg orally daily throughout the 14-day cycle.
  
  
  RESULTS
  Forty-five patients were enrolled and were assessable for toxicity. Forty-three patients were assessable for response. Thirty-one of the 43 patients (72%) had either a complete or partial response by the Response Evaluation Criteria in Solid Tumors. Median overall survival was 20.5 months. Median time to progression was 9.3 months. Commonly encountered grade 3 or 4 toxicities included diarrhea in 67% of patients and neutropenia in 60%. Grade 2 acneiform skin rash typical of gefitinib occurred in 60% of patients.
  
  
  CONCLUSIONS
  IFOX is an active first-line regimen in patients with metastatic colorectal adenocarcinoma, showing higher response rates but also increased toxicities compared with FOLFOX-4 alone in a similar patient population.
authors.affiliation: Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5151, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Fisher
authors.forename: Timothy
authors.initials: T
authors.lastname: Kuo
authors.forename: Meghan
authors.initials: M
authors.lastname: Ramsey
authors.forename: Erich
authors.initials: E
authors.lastname: Schwartz
authors.forename: Robert V
authors.initials: RV
authors.lastname: Rouse
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Cho
authors.forename: Joanne
authors.initials: J
authors.lastname: Halsey
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D000077156:Gefitinib; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D000077150:Oxaliplatin; D002955:Leucovorin; D000077156:Gefitinib; D005472:Fluorouracil