Transarterial Embolization Alone Versus Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma

Summary

Developed in Japan in the 1980s, TACE became the most frequent treatment for unresectable hepatocellular carcinoma (HCC) in patients with preserved hepatic function after 2002, when two radiochemotherapies (RCTs) showed survival benefits for HCC patients who underwent conventional Lipiodol-based TACE (cTACE). Nowadays, nearly half of HCC patients undergo this procedure during their clinical history. In the last ten years, cTACE has been challenged by an alternative procedure, drug-eluting beads-TACE (DEB-TACE), after the introduction of calibrated embolizing microspheres loaded with a chemotherapeutic agent. DEB-TACE is considered to be less toxic and better standardized than cTACE, with reported no differences in patient survival. Since 2006, DEB-TACE has become the standard in many centers worldwide. Though, the need of adding doxorubicin to small beads embolization alone (TAE) remains unsettled. Though cTACE/DEB-TACE and TAE have been compared in several RCTs, no study demonstrated a clear survival benefit associated with the former.

Our study aims to compare first-line DEB-TACE and TAE on a random sample of HCC with the hypothesis that the addition of drug to embolization with small size beads is not associated with a survival benefit when compared to embolization alone performed with tiny calibrated microspheres. HCC is considered a chemo-resistant tumor and to date there is no clear evidence of benefits in associating anticancer agents to TAE. On the other hand, the optimal size of embolic agents has still to be defined. A comparative evaluation of TACE and TAE is essential for two additional reasons: a) it is still unclear whether side effects following embolization procedures are related to the embolization itself, to drug addition or both; b) DEB-TACE procedure is more expensive than TAE and, given the current attention on cancer-related health care cost control, identification of opportunities for cost savings in HCC treatments of an increasingly common cancer would be valuable.

Conditions

• Carcinoma, Hepatocellular

Interventions

COMBINATION_PRODUCT

DEB-TACE

The chemotherapy used in this arm is the Doxorubicin that will be carried into the tumor by Embozene TANDEM® (Boston Scientific) microspheres. TANDEM® embozene microspheres are made of non-resorbable, biocompatible, hydrogel microspheres, subjected to precision calibration and coated with an inorganic perfluorate polymer (Polyzene®-F). TANDEM® embozene microspheres are available in three different sizes, in 2 ml and 3 ml volumes of product and are supplied in preloaded vials and syringes.The maximum loadable amount on the hydrospheres 50 mg of Doxorubicina for ml. The maximum injectable dose of Doxorubicin for each treatment is 150 mg and therefore the maximum amount of microspheres that can be used for each treatment is 3 ml. The size of microspheres that will be used in this study is up to 100 ± 25 μm.

DEVICE

TAE

The TAE will be performed with Embozene microspheres (Boston Scientific). Embozene microspheres are spherical particles of hydrogel, precisely calibrated, biocompatible, non-absorbable and coated with a perfluorinated inorganic polymer (Polyzene®-F). This medical device is available in various sizes; in this study, to avoid that the particle size exceeds the one used for the treatment of arm A, it will be possible to use microspheres with dimensions up to 100 μm (range 75 ± 125 μm). Embozene microspheres are offered in vials containing 1 ml of suspended product in physiological saline solution for apyrogenic sterile transport. The total volume of the Embozene microspheres, including the transport solution, is about 7 ml. To this product it is necessary to add an appropriate amount of non-ionic contrast medium in order to obtain a homogeneous suspension and with good visibility during the injection under fluoroscopy.

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna

  lead OTHER

Principal Investigators

• Rita Golfieri, Professor · IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-12-04

Primary Completion

2022-04-30

Completion

2022-04-30

Countries

• Italy

Study Locations