July 7, 2011

Largest Multi-Centre Evaluation of Radioembolization Using Sir-Spheres for Patients With Inoperable Primary Liver Cancer Published in Hepatology

PAMPLONA, Spain, July 7, 2011 /PRNewswire/ --

Results of the multi-centre European Network on Radioembolization with
Yttrium-90 Resin Microspheres (ENRY) analysis of the long-term outcomes
related to survival and safety of radioembolization using SIR-Spheres in
patients with inoperable primary liver tumours were published on-line today
in Hepatology, the peer-reviewed journal of the American Association of the
Study of Liver Diseases.[1]

Evaluation of 325 patients with inoperable primary liver cancer
(unresectable hepatocellular carcinoma), who were treated by teams of liver
specialists, oncologists, interventional radiologists and nuclear medicine
physicians at eight centres in Germany, Italy and Spain, provided "robust
evidence of the survival outcomes achieved with radioembolization, including
patients with advanced disease and few treatment options," said Bruno
Sangro, MD, PhD, Professor of Hepatology in the Liver Unit of the Clinical
University of Navarra, Pamplona, Spain, and chair of the ENRY group.

About Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) occurs in people whose livers have become
severely damaged or cirrhotic, due to conditions such as hepatitis and
alcoholism. It is one of the ten most-common cancers in the world, with
nearly 750,000 cases diagnosed annually, and the third-leading cause of
cancer deaths.[2] It occurs with greatest frequency in regions where
hepatitis is most often diagnosed, such as in Asia Pacific and Southern

Hepatocellular cancer can be cured only by surgery, either by resecting
the diseased parts of the liver, or by transplantation with a liver from a
healthy donor. These interventions, however, are inappropriate for the great
majority of patients, whose survival may range from a few months to two or
more years depending largely on the state of their liver at the time of
their diagnosis and the extent of tumour invasion.

Findings of the ENRY Evaluation

The majority of the patients (82.5%) evaluated by the ENRY group had
liver disease that was reasonably-well compensated (Child-Pugh class A),
with underlying cirrhosis (78.5%) and good ECOG Performance status (ECOG
0-1: 87.7%). However, many of them had multiple tumour nodes (75.9%), with
disease present in both lobes of the liver (53.1%) and/or occlusion of the
portal vein (the vessel that transports blood from the gastrointestinal
tract to the liver) in either a branch of the vein (13.5%) or the main
vessel (9.8%).

Over 40 per cent of the patients (41.5%) had progressed following one or
more other treatments prior to receiving radioembolization with SIR-Spheres
(yttrium-90 resin microspheres; Sirtex Medical Limited, Sydney, Australia),
including surgery or liver transplantation, percutaneous procedures such as
ethanol injection or radiofrequency ablation of individual liver tumours, or
vascular procedures such as transarterial embolisation (TAE) or
chemoembolisation (TACE) that block the liver arteries that feed tumours.

Using Barcelona Clinic Liver Cancer (BCLC) staging criteria, the vast
majority of patients evaluated by the ENRY group had either advanced (BCLC
C: 56.3%) or intermediate (BCLC B: 26.8%) disease.

The patients who received radioembolization (also called selective
internal radiation therapy or SIRT) were administered a median dose of 1.6
GBq of beta-radiating yttrium-90 resin microspheres, predominately as a
single procedure delivered transarterially to the liver via a catheter
through the femoral and hepatic arteries. The median overall survival of the
SIRT-treated patients evaluated by the ENRY group was 12.8 months. Survival
varied significantly by disease stage: 24.4 months for patients in BCLC A;
16.9 months in BCLC B; and 10.0 months in BCLC C.

"As ENRY was not a prospective study, our findings must be interpreted
conservatively," Professor Sangro explained. "What we can say, based on our
evaluation of a broad range of patients with HCC treated in routine clinical
practice, is that radioembolization using SIR-Spheres directly targets
tumours and spares viable liver tissue, which enables us to reduce the
burden of disease and potentially increase both the patient's survival and
quality of life. The greatest survival benefit can be expected in those
patients with better performance status, fewer tumour nodules and no
occlusion of the portal vein.

"It is also clear from our analysis," he added, "that radioembolization
may be particularly helpful in four specific patient populations. These
include, firstly, patients who might otherwise be considered for TACE but
may benefit more from SIR-Spheres; patients who are poor candidates for TACE
due to the high number of tumour nodules (>5) or spread to both lobes of the
liver; patients who have previously failed TACE; and, finally, patients who
are ineligible for TACE because of portal vein occlusion. These patients
have few other treatment options."

Other treatment options that have been demonstrated to extend survival
for patients with inoperable HCC include TACE, which requires repeated
interventional procedures and hospitalisation due to the resulting
post-embolisation syndrome; and sorafenib, an oral medication taken twice
daily which can give side effects leading to discontinuation of the drug in
more than a third of patients (38%).[3]

The ENRY collaboration found that radioembolization was very
well-tolerated by these otherwise ill patients. More than half (54.5%)
experienced fatigue; around one third (32.0%) reported nausea or vomiting;
while slightly more than a quarter (27.1%) reported abdominal pain and one
in ten reported a mild fever. These symptoms were transient in all cases.

A very small number of patients (3.7%) suffered from gastrointestinal
ulceration, which can occur when some microspheres inadvertently pass into a
gastric artery.

"Based on the ENRY evaluation," Prof Sangro concluded, "we believe that
radioembolization merits routine use in a number of patients with primary
liver cancer. Radioembolization may also be a synergistic option when
combined with newer pharmaceutical treatments, such as the tyrosine kinase
inhibitor, sorafenib."

Physicians and patients interested in participating in either of two
recently-initiated randomised controlled trials of radioembolization using
SIR-Spheres may learn more at:

        - http://www.soramic.de - the SORAMIC trial (
          http://www.clinicaltrials.gov identifier NCT01126645) is being conducted
          in Europe on SIR-Spheres combined with sorafenib compared to sorafenib
          alone in patients with HCC;
        - http://www.sirvenib.com - the SIRveNIB trial (
          http://www.clinicaltrials.gov identifier NCT01135056) is being conducted
          in Asia Pacific and is comparing SIR-Spheres to sorafenib in patients
          with HCC.

For Further Information:

SIR-Spheres are fully FDA-approved and are indicated in the U.S. for the
treatment of non-resectable metastatic liver tumours from primary colorectal
cancer in combination with intra-hepatic artery chemotherapy using

SIR-Spheres are also approved for use in Australia, the European Union
(CE Mark), New Zealand, Switzerland, Turkey and several other countries for
the treatment of unresectable liver tumours.

Downloadable images, media background information, a mode of action
video and further supporting materials are available online at


        1) Sangro B, Carpanese L, Cianni R et al on behalf of European
          Network on Radioembolization with Yttrium-90 resin microspheres (ENRY).
          Survival after [90]Y resin microsphere radioembolization of
          hepatocellular carcinoma across BCLC stages: A European evaluation.
          Hepatology 2011; ePub doi: 10.1002/hep.24451.
        2) GLOBOCAN. Liver Cancer Incidence and Mortality Worldwide in
          2008. http://globocan.iarc.fr/factsheets/cancers/liver.asp accessed
          28 June 2011.
        3) Llovet J, Ricci S, Mazzaferro V et al for the SHARP
          Investigators Study Group. Sorafenib in advanced hepatocellular
          carcinoma. New England Journal of Medicine 2008; 359: 378-390.

        For further information:
        Kassidie Blackstock
        Fleishman Hillard
        +1-919-457-0749 / +1-865-776-6827
        [email protected]

        Sarah Hoffman
        Aurora Healthcare Communications
        +44(0)207-148-4176 / +44(0)7809-127-499
        [email protected]