Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2015; 7(6): 47-54
Published online Jun 15, 2015. doi: 10.4251/wjgo.v7.i6.47
Locoregional therapy and systemic cetuximab to treat colorectal liver metastases
Giammaria Fiorentini, Camillo Aliberti, Donatella Sarti, Paolo Coschiera, Massimo Tilli, Luca Mulazzani, Paolo Giordani, Francesco Graziano, Alfonso Marqués Gonzalez, Raul García Marcos, Fernando Gómez Mugnoz, Maurizio Cantore, Stefano Ricci, Vincenzo Catalano, Andrea Mambrini
Giammaria Fiorentini, Donatella Sarti, Paolo Giordani, Francesco Graziano, Vincenzo Catalano, Oncology Unit, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, San Salvatore Hospital, 61122 Pesaro, Italy
Camillo Aliberti, Oncology Radiodiagnostics, Oncology Institute of Veneto, Institute for the Research and Treatment of Cancer (IRCC), 35128 Padova, Italy
Paolo Coschiera, Luca Mulazzani, Diagnostics for Images Unit and Interventional Radiology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, 61122 Pesaro, Italy
Massimo Tilli, Diagnostics for Images and Interventional Radiology, Azienda USL of Ferrara, Delta Hospital, 44023 Ferrara, Italy
Alfonso Marqués Gonzalez, Unit of Anestesiology, La Fe University Hospital and Polytechnic, 46026 Valencia, Spain
Raul García Marcos, Medical Imaging and Interventional and Vascular Radiology, La Fe University Hospital and Polytechnic, 46026 Valencia, Spain
Fernando Gómez Mugnoz, Medical Imaging Center (CDIC), Provincial Clinic Hospital , 08036 Barcelona, Spain
Maurizio Cantore, Oncology Unit, Azienda Ospedaliera “Carlo Poma”, 46010 Mantova, Italy
Stefano Ricci, Department of Vascular and Interventional Radiology, INRCA Hospital-IRCCS, 60124 Ancona, Italy
Andrea Mambrini, Oncology Unit, Carrara General Hospital, ASL 1 Massa-Carrara, 54033 Carrara, Italy
Author contributions: All authors contributed to this work.
Ethics approval: The study was reviewed and approved by the Azienda Ospedaliera “Ospedali Riuniti Marche Nord” Institutional Review Board.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: There is no conflict of interest.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Giammaria Fiorentini, Oncology Unit, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, San Salvatore Hospital, Via Lombroso 1, 61122 Pesaro, Italy. g.fiorentini@alice.it
Telephone: +39-721-364124 Fax: +39-721-364094
Received: December 30, 2014
Peer-review started: December 31, 2014
First decision: February 7, 2015
Revised: April 2, 2015
Accepted: May 5, 2015
Article in press: May 6, 2015
Published online: June 15, 2015

AIM: 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/m2 and then 250 mg/m2; 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.

CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.

Keywords: Cetuximab, Irinotecan-loaded drug-eluting beads, Hepatic metastases, Chemoembolization, Colon rectal tumor, Irinotecan

Core tip: Irinotecan-loaded drug-eluting beads (DEBIRI) has shown manageable toxicities and favorable response rates for unresectable colorectal liver metastasis (CRC-LM). This study is the first in the world investigating effectiveness and toxicity of the association DEBIRI and cetuximab (DEBIRITUX) as second line therapy of CRC-LM. Forty cases were enrolled. The overall response rate (ORR) was 50%. Most frequent side effects were: post-embolization syndrome, diarrhea, skin rushes and asthenia. The group of patients with wild type KRas had ORR significantly higher than mutant Kras. The median progression free survival was 9.8 mo and overall survival was 20.4 mo. DEBIRITUX regimen seems effective and safe after first line chemotherapy for CRC-LM.