title: A phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Gefitinib inhibits the epidermal growth factor receptor tyrosine kinase and preclinical studies indicate that it may enhance CPT-11 cytotoxicity. This randomized phase II trial investigates the feasibility and efficacy of gefitinib and 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) in patients with metastatic colorectal cancer.
  
  
  METHODS
  Patients were randomized to FOLFIRI +/- gefitinib 250 mg daily p.o. Patients randomized to FOLFIRI + gefitinib without disease progression after 6 months continued to receive gefitinib alone until disease progression.
  
  
  RESULTS
  From October 2002 to September 2004, 100 patients were enrolled. Twenty-three patients (47.9%) in the FOLFIRI arm and 23 (45.1%) in the FOLFIRI + gefitinib arm experienced an objective response. The median progression-free survival and overall survival were 8.3 and 18.6 months in the FOLFIRI arm, and 8.3 and 17.1 months in the FOLFIRI + gefitinib arm, respectively. In the combination arm, grades 3-4 adverse events were experienced by 35 (67.3%) patients versus 25 patients (52.1%) in the FOLFIRI arm; 12 patients (23.1%) withdrew for an adverse event in the FOLFIRI + gefitinib arm and 5 (10.4%) in the FOLFIRI arm.
  
  
  CONCLUSIONS
  These data show that adding gefitinib to FOLFIRI does not improve the efficacy of FOLFIRI regimen. These disappointing results could be related to the high toxicity observed that led to significant dose reductions and delays.
authors.affiliation: Unità Operativa di Oncologia e Ematologia, Istituto Clinico Humanitas, Rozzano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: A
authors.initials: A
authors.lastname: Comandone
authors.forename: L
authors.initials: L
authors.lastname: Rimassa
authors.forename: C
authors.initials: C
authors.lastname: Granetti
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: C
authors.initials: C
authors.lastname: Oliva
authors.forename: M
authors.initials: M
authors.lastname: Ronzoni
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.forename: M
authors.initials: M
authors.lastname: Zuradelli
authors.forename: E
authors.initials: E
authors.lastname: Mari
authors.forename: T
authors.initials: T
authors.lastname: Pressiani
authors.forename: C
authors.initials: C
authors.lastname: Carnaghi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011799:Quinazolines; D002955:Leucovorin; D000077156:Gefitinib; D005472:Fluorouracil; D002166:Camptothecin