Irinotecan-Eluting 75-150-μm Embolics Lobar Chemoembolization in Patients with Colorectal Cancer Liver Metastases: A Prospective Single-Center Phase I Study

J Vasc Interv Radiol. 2018 Dec;29(12):1646-1653.e5. doi: 10.1016/j.jvir.2018.08.010. Epub 2018 Oct 15.

Abstract

Purpose: The primary end point of this trial was to determine the feasibility and safety of transarterial chemoembolization with the use of 75-150-μm drug-eluting embolics loaded with irinotecan (DEE-IRI) for the treatment of metastatic colorectal cancer (CRC) refractory to systemic chemotherapy.

Materials and methods: Fourteen patients (mean age 57.9 years) with liver-dominant metastatic disease (14.3% unilobar, 85.7% bilobar), who had failed at least 1 line of chemotherapy, were enrolled and received up to 4 (mean 2.3) cycles of DEE-IRI lobar transarterial chemoembolization. Technical complications and adverse events were recorded, and response was assessed by means of imaging-based criteria. Levels of irinotecan and angiogenesis biomarkers in the serum were measured at multiple time points.

Results: Thirty-two DEE-IRI transarterial chemoembolizations were successfully performed, and the full dose (100 mg) was delivered in all cases. The only grade 3-4 toxicity was abdominal pain (29%). One patient had objective response according to the Response Evaluation Criteria in Solid Tumors and World Health Organization, and 3 patients had objective response according to the European Association for the Study of the Liver. The median overall survival was 18.14 months, and the 1-year survival was 65%. The average plasma Cmax of the active metabolite was 41.5 ± 26.1 ng/mL, with average Tmax of 1.3 ± 0.5 hours. The treatment significantly reduced levels of vascular endothelial growth factor receptor 1 (VEGFR1) at 24 hours.

Conclusions: Lobar transarterial chemoembolization with the use of DEE-IRI is a technically feasible and well tolerated palliative treatment for patients with refractory liver-predominant CRC metastatic disease and has acceptable pharmacokinetics. VEGFR1 is a potential biomarker for predicting treatment efficacy and risk of adverse events.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Biomarkers, Tumor / blood
  • Chemoembolization, Therapeutic / adverse effects
  • Chemoembolization, Therapeutic / methods*
  • Chemoembolization, Therapeutic / mortality
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Connecticut
  • Drug Carriers*
  • Feasibility Studies
  • Female
  • Humans
  • Irinotecan / administration & dosage*
  • Irinotecan / adverse effects
  • Irinotecan / blood
  • Irinotecan / pharmacokinetics
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Male
  • Microspheres
  • Middle Aged
  • Palliative Care
  • Prospective Studies
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Drug Carriers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Irinotecan
  • FLT1 protein, human
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2