title: The effect of doxorubicin loading on response and toxicity with drug-eluting embolization in resectable hepatoma: a dose escalation study.
abstract: OBJECTIVE
  The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC).
  
  
  METHODS
  Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals.
  
  
  RESULTS
  Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor.
  
  
  CONCLUSIONS
  Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin.
authors: Department of Interventional Radiology, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Darren
authors: D
authors: Klass
authors: Department of Pathology, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: David
authors: D
authors: Owen
authors: Department of Hepatobiliary Surgery, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Andrezj
authors: A
authors: Buczkowski
authors: Department of Hepatobiliary Surgery, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Stephen W
authors: SW
authors: Chung
authors: Department of Hepatobiliary Surgery, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Charles H
authors: CH
authors: Scudamore
authors: Division of Gastroenterology, University of British Columbia, Faculty of Medicine, BC Cancer Agency, Vancouver, BC, Canada.
authors: Alan A
authors: AA
authors: Weiss
authors: Division of Gastroenterology, University of British Columbia, Faculty of Medicine, BC Cancer Agency, Vancouver, BC, Canada.
authors: Eric M
authors: EM
authors: Yoshida
authors: Division of Gastroenterology, University of British Columbia, Faculty of Medicine, BC Cancer Agency, Vancouver, BC, Canada.
authors: Jo-Ann E
authors: JA
authors: Ford
authors: Department of Interventional Radiology, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors: Stephen
authors: S
authors: Ho
authors: Department of Interventional Radiology, University of British Columbia, Faculty of Medicine, Vancouver General Hospital, Vancouver, BC, Canada david.liu@vch.ca.
authors: David M
authors: DM
authors: Liu
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Hepatocellular carcinoma; chemoembolization; drug eluting beads; imaging; lipiodol; microsphere; pathology; response