In a French phase II trial (PACHA-01) reported in the Journal of Clinical Oncology, Gelli et al found that adjuvant hepatic infusion of oxaliplatin improved hepatic recurrence–free survival vs intravenous (IV) oxaliplatin, both combined with fluorouracil/leucovorin (LV5FU2), after curative-intent surgery for four or more colorectal liver metastases.
Study Details
In the multicenter trial, 99 patients were randomly assigned between June 2015 and December 2020 to receive oxaliplatin at 85 mg/m2 over 6 hours via infusion and 4 hours thereafter via hepatic arterial infusion (n = 50) or via 2-hour IV infusion (n = 49). Both groups received concomitant IV LV5FU2 (2-hour leucovorin at 400 mg/m2 concomitant with oxaliplatin) followed by bolus (400 mg/m2) and then infusional (2,400 mg/m2) fluorouracil over 46 hours. Treatment was repeated every 14 days. The primary outcome measure was hepatic recurrence–free survival.
Key Findings
Patients in both groups had a median of six liver metastases. Four or more cycles of adjuvant chemotherapy were received by 81% of patients in the hepatic arterial infusion group and 78% in the IV group (P = .75).
Median follow-up was 59 months (interquartile range = 45–71 months). Median hepatic recurrence–free survival was 25 months (95% confidence interval [CI] = 16–37 months) in the hepatic arterial infusion group vs 12 months (95% CI = 8–19 months) in the IV group (hazard ratio [HR] = 0.63, 95% CI = 0.40–0.99, P = .047). Median recurrence-free survival was 14 months (95% CI = 10–20 months) in the hepatic arterial infusion group vs 9 months (95% CI = 7–11 months) in the IV group (HR = 0.63, 95% CI = 0.41–0.97, P = .03). Median overall survival was 74 months (95% CI = 51 months to not defined) in the hepatic arterial infusion group vs 57 months (95% CI = 37–69 months) in the IV group (HR = 0.61, 95% CI = 0.33–1.12, P = .11); 5-year rates were 62% vs 47%.
Grade 3 to 4 adverse events occurred in 58% of hepatic arterial infusion patients and 32% of IV patients (P = .02). No treatment-related deaths were reported.
The investigators concluded: “Adjuvant oxaliplatin [hepatic arterial infusion] plus LV5FU2 improves [hepatic recurrence-free survival] after curative-intent surgery of [colorectal liver metastases] in high-risk patients, with an acceptable safety profile. These results support further evaluation in a phase III trial.”
Maximiliano Gelli, MD, PhD, of the Department of Anaesthesia, Surgery and Interventional Radiology, Gustave Roussy Hospital, University of Paris–Saclay, Villejuif, France, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the French National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
