title: Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study.
abstract: BACKGROUND
  Metastases to the liver receive most of their blood supply from the arterial route, therefore for patients with hepatic metastases from large bowel cancer, hepatic arterial infusion adopting drug-eluting beads preloaded with irinotecan (DEBIRI) may offer a chance of cure.
  
  
  METHODS
  In a multi-institutional study, 74 patients were randomly assigned to receive DEBIRI (36) versus systemic irinotecan, fluorouracil and leucovorin (FOLFIRI, 38). The primary end-point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost and influence of molecular markers.
  
  
  RESULTS
  At 50 months, overall survival was significantly longer for patients treated with DEBIRI than for those treated with FOLFIRI (p=0.031, log-rank). Median survival was 22 (95% Confidence Interval CI=21-23) months, for DEBIRI and 15 (95% CI=12-18) months for FOLFIRI. Progression-free survival was 7 (95% CI=3-11) months in the DEBIRI group compared to 4 (95% CI=3-5) months in the FOLFIRI group and the difference between groups was statistically significant (p=0.006, log-rank). Extrahepatic progression had occurred in all patients by the end of the study, at a median time of 13 (95% CI=10-16) months in the DEBIRI group compared to 9 (95% CI 5-13) months in the FOLFIRI group. A statistically significant difference between groups was not observed (p=0.064, log-rank).The median time for duration of improvement to quality of life was 8 (95% CI=3-13) months in the DEBIRI group and 3 (95% CI=2-4) months in the FOLFIRI group. The difference in duration of improvement was statistically significant (p=0.00002, log-rank).
  
  
  CONCLUSIONS
  This study showed a statistically significant difference between DEBIRI and FOLFIRI for overall survival (7 months), progression-free survival (3 months) and quality of life (5 months). In addition, a clinically significant improvement in time to extrahepatic progression (4 months) was observed for DEBIRI, a reversal of the expectation for a regional treatment. This suggests a benefit of DEBIRI treatment over standard chemotherapy and serves to establish the expected difference between these two treatment options for planning future large randomized studies.
authors.affiliation: Department of Oncology-Hematology, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy. g.fiorentini@alice.it
authors.forename: Giammaria
authors.initials: G
authors.lastname: Fiorentini
authors.forename: Camillo
authors.initials: C
authors.lastname: Aliberti
authors.forename: Massimo
authors.initials: M
authors.lastname: Tilli
authors.forename: Luca
authors.initials: L
authors.lastname: Mulazzani
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Paolo
authors.initials: P
authors.lastname: Giordani
authors.forename: Andrea
authors.initials: A
authors.lastname: Mambrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Montagnani
authors.forename: Paolo
authors.initials: P
authors.lastname: Alessandroni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Paolo
authors.initials: P
authors.lastname: Coschiera
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin