Adjuvant Hepatic Arterial Infusion Pump Chemotherapy Without Systemic Therapy After Repeat Local Treatment for Patients With Liver-only Recurrence of Colorectal Cancer

BACKGROUND: Approximately 30% of patients develop liver-confined recurrences after local treatment for colorectal liver metastases (CRLM), which may be reduced by adjuvant therapy. Hepatic arterial infusion pump (HAIP) chemotherapy delivers high-dose liver-directed chemotherapy. OBJECTIVE: To investigate adjuvant HAIP chemotherapy without systemic therapy in patients with resectable liver-confined recurrence after prior local treatment of CRLM. METHODS: This multicenter, single-arm phase II trial enrolled patients with resectable recurrent CRLM across 3 centers in the Netherlands. Patients with prior or present extrahepatic disease were excluded. Adjuvant HAIP with floxuridine was administered up to 6 cycles. The primary endpoint was hepatic disease-free survival (hDFS) estimated using the Kaplan-Meier method, with a prespecified efficacy boundary of 36 months. RESULTS: Forty-five patients underwent local treatment followed by adjuvant HAIP chemotherapy without systemic therapy. Twenty-eight patients(62%) were treated for a first recurrent CRLM, and 17 patients for a second or higher. Twenty-five patients (56%) had ≥3 CRLM. All patients started HAIP chemotherapy, with a median of 6 cycles (interquartile range: 4 to 6). After a median follow-up of 38.7 months (95% CI: 33.0-42.3), the median hDFS was 16.5 months (95% CI: 9.1-25.8). The median progression-free survival was 14.0 months (95% CI: 7.7-23.0), and the 3-year overall survival was 71% (95% CI: 58%-87%). Initial recurrence included the liver in 23 patients (51%). HAIP implantation-related complications (Clavien-Dindo grade ≥3) occurred in 4 patients (9%), and HAIP chemotherapy-related complications (Common Terminology Criteria for Adverse Events grade ≥3) occurred in 6 patients (13%). Biliary sclerosis occurred in 4 patients; 3 required stent placement. CONCLUSION: Adjuvant HAIP chemotherapy without systemic therapy did not achieve the hypothesized hDFS in patients undergoing repeat local treatment for recurrent CRLM.