Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Abstract

Background Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. Patients and Methods A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle–Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. Results After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0–39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. Conclusion HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.

Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti‐PD‐1 immunotherapy for unresectable intrahepatic cholangiocarcinoma

“…14,15,24,28 Furthermore, a meta-analysis showed that HAIC achieved a pooled PR and the weighted median PFS of 52.7% and 11.4 months, respectively. 29 Despite different criteria for the response rate, treatment efficacy of the HAIC-based triple-combination therapy in our study was better than that of the majority of previous studies. However, it should be noted that in previous studies, patients had received surgical HAIC pump placement and regional lymphadenectomy, unlike our patients.…”

“…In previous studies on HAIC for ICC, the PR based on RECIST was reported to be 27.3%–59.5%, and the median PFS was 7.4–12.8 months 14,15,24,28 . Furthermore, a meta‐analysis showed that HAIC achieved a pooled PR and the weighted median PFS of 52.7% and 11.4 months, respectively 29 . Despite different criteria for the response rate, treatment efficacy of the HAIC‐based triple‐combination therapy in our study was better than that of the majority of previous studies.…”

The Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Based on FOLFIRI for Advanced Intrahepatic Cholangiocarcinoma as Second-Line and Successive Treatment: A Real-World Study

“…This small sample study suggested the feasibility of HAIC in iCCA treatment. A recent meta-analysis (pooling data from 9 studies that had enrolled a total of 154 patients) showed that hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA was associated with a favorable 3-year OS of 39.5% (95% CI 31.5–47.4%) compared with systemic chemotherapy, with no patients surviving beyond 3 years observed in the ABC trial [ 31 ]. Therefore, we further explored the application of HAIC based on the FOLFIRI regimen in iCCA patients as a second-line and successive therapy.…”

Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians

“…21 Recent advances in our understanding of the genomic landscape in ICC have also led to the implementation of targeted therapies for up to 40% of patients with actionable alterations, including those in isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR), but resistance to these agents typically develops within months of initiation, and survival remains poor. [22][23][24][25] Emerging effective treatment strategies that combine systemic and locoregional therapies, such as radioembolization or hepatic artery infusion (HAI), have also been developed 20,26,27 (Figure 1).…”