title: Locoregional therapy and systemic cetuximab to treat colorectal liver metastases.
abstract: OBJECTIVE
  To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases.
  
  
  METHODS
  Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m(2) and then 250 mg/m(2); good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS).
  
  
  RESULTS
  Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy.
  
  
  CONCLUSIONS
  DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Giammaria
authors.initials: G
authors.lastname: Fiorentini
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Aliberti
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Sarti
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Coschiera
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tilli
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Mulazzani
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giordani
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Alfonso Marqués
authors.initials: AM
authors.lastname: Gonzalez
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Raul García
authors.initials: RG
authors.lastname: Marcos
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Fernando Gómez
authors.initials: FG
authors.lastname: Mugnoz
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cantore
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ricci
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.affiliation: Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", San Salvatore Hospital, 61122 Pesaro, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mambrini
keywords: Cetuximab; Chemoembolization; Colon rectal tumor; Hepatic metastases; Irinotecan; Irinotecan-loaded drug-eluting beads