In a Dutch phase II trial (PUMP-2) reported in the Journal of Clinical Oncology, Franssen et al found that use of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine, with or without concomitant gemcitabine, plus cisplatin showed good activity and improved overall survival in patients with unresectable intrahepatic cholangiocarcinoma vs a historical cohort treated with gemcitabine plus cisplatin alone.
Study Details
In the multicenter study, 50 patients with or without prior systemic therapy were to receive up to six cycles of HAIP floxuridine plus up to eight concurrent cycles of standard gemcitabine plus cisplatin. HAIP floxuridine was given in a 4-week cycle, in which the pump reservoir was filled with floxuridine (0.12 mg/kg/day) on day 1; on day 15, the pump was emptied and refilled with heparin and saline solution and given for 2 weeks. Patients who had not received prior gemcitabine plus cisplatin received cisplatin at 25 mg/m2 followed by gemcitabine at 800 mg/m2 every 2 weeks during each subsequent pump access. The primary outcome measure was 1-year overall survival, compared with a rate of 47% observed in a historical gemcitabine plus cisplatin cohort.
Key Findings
Between January 2020 and September 2022, 50 patients had a pump placed. Two patients (4%) did not start HAIP floxuridine (one patient died due to COVID-19 and one patient had hepatic arterial dissection). The remaining 48 patients (96%) started HAIP chemotherapy, combined with systemic gemcitabine plus cisplatin in the 37 patients (74%) who had not previously received the combination.
In intention-to-treat analysis, 22 patients (44%) had a partial response and 42 (84%) had disease control at 6 months. Conversion to resection occurred in five patients (10%), with one having a complete pathologic response.
Median overall survival was 22.3 months (95% confidence interval [CI] = 19.7–35.9 months). The 1-year overall survival rate was 80.0% (95% CI = 69.6%–91.9%), which was superior to the historical control rate of 47% (P < .001). At 3 years, overall survival was 31.5% (95% CI = 20.4%–48.6%), exceeding the 3-year historical control rate of 3%.
Median overall survival was similar with HAIP chemotherapy with gemcitabine plus cisplatin as initial treatment vs HAIP chemotherapy after previous systemic treatment (25.3 vs 22.1 months, P = .645).
A total of six patients (12%) had a HAIP-specific complication. Grade 3 or 4 adverse events associated with floxuridine occurred in seven patients (14%).
The investigators concluded: “Combining HAIP chemotherapy with floxuridine and systemic [gemcitabine plus cisplatin] in patients with unresectable liver-confined [intrahepatic cholangiocarcinoma] had a 1- and 3-year [overall survival] superior to [gemcitabine plus cisplatin] alone in historical cohorts.”
Bas Groot Koerkamp, MD, PhD, of the Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by KWF Dutch Cancer Society. For full disclosures of all study authors, visit ascopubs.org.
