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Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

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Abstract

Purpose

To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial.

Methods

Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria.

Results:

DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect.

Conclusions

Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

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Acknowledgments

This study was partially funded by National Institutes of Health Grant No. R01 CA160771-2 and BioCompatibles UK Ltd. Clinical Trials.gov trial no. NCT00730483. Previous presentations include the following: (1) American Society of Clinical Oncology, Gastrointestinal Cancers Symposium, San Francisco, CA, January 20 to 22, 2011; (2) Cardiovascular and Interventional Radiological Society of Europe, 2011, Sept 10–14, and (3) Society of Interventional Radiology, 36th Annual Scientific Meeting, Chicago, IL, 2011.

Conflict of interest

Nikhil Bhagat, Mingde Lin, and Jean-Francois Geschwind were partially funded by National Institutes of Health Grant No. R01 CA 160771-2. Jean-Francois Geschwind was partially funded by Biocompatibles UK Ltd.

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Authors and Affiliations

  1. Division of Vascular and Interventional Radiology, Department of Radiology, Johns Hopkins University Medical Center, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, Baltimore, MD, 21287, USA

    Nikhil Bhagat, Diane K. Reyes, Ihab Kamel & J. F. Geschwind

  2. Clinical Informatics, Interventional, and Translational Solutions (CIITS), Philips Research North America, Briarcliff, NY, 10510, USA

    Mingde Lin

  3. Department of Surgery, Johns Hopkins University Medical Center, Baltimore, MD, 21287, USA

    Timothy M. Pawlik

  4. Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21287, USA

    Constantine Frangakis

Authors
  1. Nikhil Bhagat
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  2. Diane K. Reyes
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  3. Mingde Lin
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  4. Ihab Kamel
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  5. Timothy M. Pawlik
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  6. Constantine Frangakis
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  7. J. F. Geschwind
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Corresponding author

Correspondence to J. F. Geschwind.

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Bhagat, N., Reyes, D.K., Lin, M. et al. Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury. Cardiovasc Intervent Radiol 36, 449–459 (2013). https://doi.org/10.1007/s00270-012-0424-y

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