Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury.
OBJECTIVE
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.
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. nbhagat1@jhmi.edu
Nikhil
N
Bhagat
Diane K
DK
Reyes
Mingde
M
Lin
Ihab
I
Kamel
Timothy M
TM
Pawlik
Constantine
C
Frangakis
J F
JF
Geschwind
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001659:Biliary Tract / Q000293:injuries*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects*; D003287:Contrast Media; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008863:Microspheres; D018358:Neuroendocrine Tumors / Q000473:pathology*; D018579:Patient Selection; D016896:Treatment Outcome; D047368:Tumor Burden
D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D004317:Doxorubicin