In a single-center phase II trial reported in JAMA Oncology, Andrea Cercek, MD, and colleagues found that hepatic arterial infusion of floxuridine in combination with systemic gemcitabine/oxaliplatin produced high response and disease control rates and was associated with promising overall survival among patients with unresectable intrahepatic cholangiocarcinoma.
Andrea Cercek, MD
As noted by the investigators, intrahepatic cholangiocarcinoma has a poor prognosis, with a median overall survival of 11 months having been observed.
Study Details
The study involved 38 evaluable patients treated at Memorial Sloan Kettering Cancer Center between May 2013 and June 2019. Patients with resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted; those with distant metastatic disease were excluded.
Patients received a hepatic arterial infusion of floxuridine ([0.12 mg/kg × kg × 30]/pump flow rate) for 14 days starting on day 1 in 4-week cycles, with gemcitabine at 800 mg/m2 and oxaliplatin at 85 mg/m2 given on day 15 of the first cycle and then every 2 weeks with each subsequent pump access. The primary outcome was progression-free survival of 80% at 6 months.
Responses and Survival
The median follow-up was 30.5 months. Partial radiographic response was observed in 22 patients (58%), with 32 patients (84%) achieving disease control at 6 months. Response was sufficient to allow resection in four patients, with one patient having a complete pathologic response.
Median progression-free survival was 11.8 months, with a 6-month rate of 84.1%. Median overall survival was 25.0 months, with a 1-year rate of 89.5%. No significant difference in 24-month overall survival was observed between 18 patients with resectable regional lymph nodes vs patients with node-negative disease (50% vs 60%, P = .66). Among 33 patients with available data on somatic mutations, those with IDH1/2-mutated tumors had improved survival vs those with wild-type tumors (2-year overall survival = 90% vs 33%, P = .01).
KEY POINTS
- Treatment produced partial response in 58% of patients and disease control in 84%.
- Median progression-free survival was 11.8 months and median overall survival was 25.0 months.
Adverse Events
In the initial 3 months of therapy, 27 patients (71%) received the expected dose of floxuridine, with this number decreasing to 18 patients (47%) over the next 6 months. The most common causes of discontinuation or dose reduction of floxuridine included elevated liver function tests and abdominal pain. The most common grade 3 or 4 adverse events were elevated alanine aminotransferase (47%; 5% grade 4), elevated aspartate aminotransferase (39%; 5% grade 4), elevated bilirubin (23%; 5% grade 4), and anemia (16%). Grade 4 events led to removal of four patients (11%) from the study (portal hypertension in one, gastroduodenal artery aneurysm in two, and infection in pump pocket in one).
The investigators concluded: “Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable intrahepatic cholangiocarcinoma; further evaluation is warranted.”
William Jarnagin, MD, of the Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by a National Cancer Institute grant and the Kronthal Family. For full disclosures of the study authors, visit jamanetwork.com.
