title: Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin-Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma.
abstract: OBJECTIVE
  This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100 μm for hepatocellular carcinoma.
  
  
  METHODS
  A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEM™ loaded with 150 or 100 mg of doxorubicin.
  
  
  RESULTS
  The mean diameter of the tumors was 7.28 ± 2.09 cm (range 4-12) and distribution dominant/multiple 51.9/48.1 %. Child A/B distribution was 32/20 (61.5/38.5 %) and etiology HBV/HCV/HBV/HCV-hemochromatosis was 61.6/9.6/9.6/15.4 %. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92 % thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7 %) in the high loading. Mean maximum plasma concentration of doxorubicin C max ± SD was 284.9 ± 276.2 ng/mL for the high and 108.5 ± 77.6 ng/mL for the low loading (p < 0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82 % at 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6 %, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups.
  
  
  CONCLUSIONS
  Initial evidence shows that (a) TANDEM™ achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity.
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece. kmalag@otenet.gr.
authors.forename: Katerina
authors.initials: K
authors.lastname: Malagari
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kiakidis
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Pomoni
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Hippokratis
authors.initials: H
authors.lastname: Moschouris
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Emmanouil
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Themis
authors.initials: T
authors.lastname: Spiridopoulos
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Vlasios
authors.initials: V
authors.lastname: Sotirchos
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Savvas
authors.initials: S
authors.lastname: Tandeles
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koundouras
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Kelekis
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Filippiadis
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Charokopakis
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Bouma
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Achilles
authors.initials: A
authors.lastname: Chatziioannou
authors.affiliation: 2nd Department of Internal Medicine, Hepatology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Dourakis
authors.affiliation: 2nd Department of Internal Medicine, Hepatology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Koskinas
authors.affiliation: Foundation Biomedical Research of Academy of Athens (FBRA), Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Karampelas
authors.affiliation: Foundation Biomedical Research of Academy of Athens (FBRA), Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tamvakopoulos
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kelekis
authors.affiliation: 2nd and 1st Department of Radiology, National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, 20 Papadiamandopoulou, 11528, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kelekis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Chemoembolization; Drug eluting beads; Hepatocellular carcinoma; Tightly calibrated microspheres