Prospective Randomised Study of Doxorubicin in the Treatment of Hepatocellular Carcinoma by Drug-Eluting Bead Embolisation

The objective of this study is to assess the safety and efficacy of DC Bead™ delivered by intra-arterial embolisation for the treatment of Hepatocellular Carcinoma


Eligibility Criteria:
Inclusion criteria

* Patients with a confirmed diagnosis of HCC according to the EASL criteria for diagnosis, see appendix 4 and staged according to the BCLC criteria.
* Patient chooses to participate and has signed the informed consent document
* Age above 18 years old
* Patients with HCC not suitable for resection or percutaneous ablation according to the BCLC Staging classification, see Figure 2.
* Patient is eligible for resection or percutaneous ablation but the treatment is unfeasible or the patient has declined. This decision must be documented in the patient's records.
* Patient is eligible for chemoembolisation prior to transplantation and the expected transplant waiting time exceeds 6 months.
* Patients who demonstrates recurrence following potentially curative treatment (resection and percutaneous ablation) who have clearly measurable disease according to RECIST or EASL
* Patients with Performance Status ECOG 0 and 1
* Patients with well preserved liver function (Child-Pugh A and B)
* Patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3 weeks.

Exclusion criteria

* Patients with another primary tumour, with the exception of conventional basal cell carcinoma or superficial bladder neoplasia
* Patients previously treated with transarterial embolisation (with or without chemotherapy).
* Patients previously treated with anthracyclines (ie doxorubicin).
* Patients' whose only measurable disease is within an area of the liver previously subjected to radiotherapy.
* Advanced liver disease:

  * Child-Pugh C,
  * active gastrointestinal bleeding,
  * encephalopathy or clinically relevant ascites.
* Bilirubin levels \>3mg/dl
* Advanced tumoural disease:

  * BCLC class C, (vascular invasion including segmental portal obstruction, extrahepatic spread or cancer-related symptoms= ECOG 2, 3 and 4) or
  * BCLC class D (WHO performance status 3 or 4, Okuda III stage) or
  * Diffuse HCC defined as \>50% tumour involvement of the whole liver
* Any contraindication for doxorubicin administration:

  * serum bilirubin \>5mg/dL,
  * WBC \<3000 cells/mm3
  * neutrophil \<1500 cells/mm3,
  * cardiac ejection fraction \<50 percent assessed by isotopic ventriculography, echocardiography or MRI
* Any contraindication for hepatic embolisation procedures:

  * porto-systemic shunt,
  * hepatofugal blood flow;
  * impaired clotting tests (platelet count \<50000/mm3, prothrombin activity \<50 percent),
  * renal insufficiency/failure, serum creatinine \> 2mg/dl (177umol/l)
  * severe atheromatosis,
  * AST and/or ALT \>5x ULN or, when greater \>250U/l
* Women who are pregnant or breast feeding
* Allergy to contrast media
* Contraindication to hepatic artery catheterisation, such as severe peripheral vascular disease precluding catheterisation
* The availability of alternative therapies those, in the judgment of the physician (referring or treating), are more appropriate for the patient
* Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk, that would preclude the safe use of DC Bead™, or TACE
* Patients who are contraindicated for MRI