Abstract
BackgroundEfficacy 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.MethodsThe 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.ResultsNine 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 Cmax 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).ConclusionSelective 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 registrationUniversity Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367; Registered date; 08,10,2014.
Highlights
Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited
Oxaliplatin regimens such as FOLFOX combined with biological agents are widely used as first-line treatment for unresectable colorectal liver metastases, resulting in high response rates of around 45 to 62% and long progression free survival (PFS) of 10 to 11 months [1, 2]
Several previous reports showed that transarterial chemoembolization (TACE) with irinotecan-loaded microspheres was effective for treating colorectal liver metastases (mCRC) after failure of standard systemic chemotherapies [4,5,6]
Summary
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. Oxaliplatin regimens such as FOLFOX (folinic acid, 5fluorouracil, and oxaliplatin) combined with biological agents are widely used as first-line treatment for unresectable colorectal liver metastases (mCRC), resulting in high response rates of around 45 to 62% and long progression free survival (PFS) of 10 to 11 months [1, 2]. Embozene TANDEM (Boston Scientific, Marlborough, MA) is a second generation drug-eluting microsphere available in a smaller, precisely calibrated 40 μm size (http://www.bostonscientific.com/en-EU/products/embo lization/embozene_tandem_microspheres.html)
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