Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer

AIM To study tumor response, and tolerability of arterially directed embolic therapy(ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases(CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients.METHODS Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status(PS), tumor marker antigens, and quality of life(QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale(PPS).RESULTS We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response(CR), 48% of partial response(PR), 8% stable disease(SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease(PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo(range 0.8-6). Median follow-up was 14 mo(0.8-25 range). ADETs were performed with no complications. Observed side effects(mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.

Multidisciplinary approach of colorectal cancer liver metastases

Large bowel cancer is a worldwide public health challenge.More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases.Selection criteria for early diagnosis,chemotherapy and surgery have been recently expanded.The definition of resectability remains unclear.The presence of metastases is the most significant prognostic factor.For this reason the surgical resection of hepatic metastases is the leading treatment.The most appropriate resection approach remains to be defined.The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes.The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies(chemoembolization,thermal ablation,arterial infusion chemotherapy) contribute to extend favorable results.Standardized evidence-based protocols are missing,hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team.This article reviews the outcomes of resection,systemic and loco-regional therapies of liver metastases originating from large bowel cancer.

Locoregional therapy and systemic cetuximab to treat colorectal liver metastases

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/m L). 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.