Phase III Randomised Controlled Trial Confirms Clinical Efficacy and Safety of Radioembolisation Using 90Y-resin Microspheres for Patients With Inoperable Colorectal Cancer Liver Metastases That Have Failed Chemotherapy

BRUSSELS, August 19, 2010 - Using the innovative technique of radioembolisation to treat patients
with inoperable colorectal cancer liver metastases who have failed all
standard-of-care chemotherapy options can more than double the time until
their disease progresses, according to the final results of a Phase III
randomised controlled trial published in the prestigious Journal of Clinical
Oncology.(1)

The prospective, randomised trial compared a protracted infusion of
5-fluorouracil (5FU) chemotherapy to the same chemotherapy in combination
with radioembolisation, also known as selective internal radiation therapy
(SIRT), using 90Y-resin microspheres (SIR-Spheres; Sirtex Medical, Sydney,
Australia). The trial was designed to assess the efficacy and safety of this
combination in patients with liver metastases from colorectal cancer and was
conducted at three Belgian university hospitals.(2)

The trial recruited 46 patients who had failed all other standard-of-care
treatments. The time to the progression of liver metastases - the primary
endpoint of the study - increased significantly from a median of 2.1 months
in patients receiving 5FU alone to 5.5 months in patients receiving
radioembolisation plus 5FU. The risk of progression was 62% lower in patients
receiving radioembolisation plus 5FU (hazard ratio 0.38; p=0.003). The time
to progression of disease anywhere in the body was also significantly longer,
from a median of 2.1 months in the 5FU control arm to 4.5 months in patients
in the radioembolisation/5FU arm (hazard ratio 0.51; p=0.03). Control of
liver metastases was also significantly increased in patients receiving
radioembolisation plus 5FU, from 35% to 85% (p=0.001). More patients in the
5FU-only control arm experienced severe side effects than those receiving
radioembolisation plus 5FU (26% versus 5%; p=0.10).

The ability to show a difference in the overall survival of patients was
blunted by the ethical design of the study, since patients receiving 5FU
alone were reassessed once their cancer progressed, and, if possible, were
treated with radioembolisation alone. Ten patients in the control arm later
received radioembolisation and 6 received further chemotherapy, as did 9
patients in the radioembolisation plus 5FU group. Median overall survival was
7.3 months in the patients receiving 5FU alone, compared to 10.0 months in
patients receiving radioembolisation plus 5FU, a difference that was not
statistically significant.

"The combination of radioembolisation using 90Y-resin microspheres and
5FU chemotherapy was well tolerated and significantly improves the outcomes
for patients compared with 5FU alone," said Dr Alain Hendlisz, chief of the
gastroenterology unit at Institut Jules Bordet in Brussels, Belgium, and lead
investigator of the trial. "The results of this randomised controlled trial
provide Level 1 evidence that radioembolisation with 90Y-resin microspheres
is a valid therapeutic option for patients with colorectal cancer liver
metastases that have failed chemotherapy."

Large international randomised controlled trials are currently evaluating
the effectiveness of radioembolisation using 90Y-resin microspheres with
first-line chemotherapy in the treatment of patients with colorectal cancer
liver metastases compared to chemotherapy alone in order to assess whether
the combination should be used as an early intervention for liver tumours.

References and notes

1. Hendlisz A, Van den Eynde M, Peeters M et al. Phase III trial
comparing protracted intravenous fluorouracil infusion alone or with
yttrium-90 resin microspheres radioembolization for liver-limited metastatic
colorectal cancer refractory to standard chemotherapy. Journal of Clinical
Oncology 2010; 28: 3687-3694.

    2. The clinical trial was conducted at the following hospitals:

    - Institut Jules Bordet, Brussels, Belgium
    - Universitair Ziekenhuis Gent, Gent, Belgium
    - University Hospital Gasthuisberg, Leuven, Belgium

For more information and to arrange interviews, contact: Maya Anaokar at Ruder Finn, Mobile: +44(0)7894-095-429, Email: manaokar at ruderfinn.co.uk