Selective TACE with irinotecan-loaded 40 μm microspheres and FOLFIRI for colorectal liver metastases: phase I dose escalation pharmacokinetic study

BACKGROUND: Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited. The aim of this study was to prospectively evaluate the feasibility, tolerability, and pharmacokinetics of selective transarterial chemoembolization (TACE) with irinotecan-loaded 40 μm microspheres combined with systemic FOLFIRI for colorectal liver metastases refractory to oxaliplatin regimen. METHODS: The dose escalation study was conducted in three patient groups with different amounts of irinotecan loaded (50, 75 and 100 mg per mL-microspheres). Selective catheterization was performed to embolize subsegments or segments of located tumors using TACE navigation system. FOLFIRI was administrated 7 days after TACE. Plasma concentration was measured before and time points after administration. RESULTS: Nine patients successfully underwent a total of 22 TACE procedures. Dose-limiting toxicity did not appear at any level. The overall response rate was 55.6%. The median progression free and overall survival were 8.1 and 18.2 months, respectively. The AUC and C(max) of plasma SN-38 per 1 mg injected irinotecan dose were significantly higher in irinotecan-loaded microspheres compared with FOLFIRI (P = 0.009 and P < 0.001, respectively). CONCLUSION: Selective TACE using 40 μm irinotecan-loaded microspheres combined with systemic FOLFIRI was feasible and safe even when a high dose of irinotecan was loaded. Irinotecan-loaded microspheres resulted in a higher plasma concentration and AUC of SN-38 than treatment with FOLFIRI. Further large scale trials to evaluate the efficacy are mandatory. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367; Registered date; 08,10,2014.