Published online Jun 15, 2015. doi: 10.4251/wjgo.v7.i6.47
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.
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.