Randomized Controlled Trial of Radioactive Resin Microspheres Demonstrates Significant Delay in Progression of Disease in Patients with Colorectal Cancer Liver Metastases who have Exhausted Chemotherapy

ORLANDO, Fla.--(Business Wire)--
The time to progression of disease in patients with colorectal cancer liver
metastases who have exhausted all chemotherapy options can be more than doubled
through the use of radioactive resin microspheres, according to the results of a
prospective randomized controlled trial presented at the 45th Annual Meeting of
the American Society of Clinical Oncology (ASCO).1 The multicenter phase III
study compared the use of 5-fluorouracil (5FU) alone to 5FU plus 90Y resin
microspheres (SIR-Spheres; Sirtex Medical, Sydney) and was conducted by a
collaboration of university hospitals in Belgium.

"Patients with colorectal cancer liver metastases who are resistant or
intolerant of chemotherapy should be considered for salvage therapy using 90Y
resin microspheres combined with 5FU-based chemotherapy," said Dr Alain
Hendlisz, Head ofDigestive Oncology and Gastroenterology at Institut Jules
Bordet Université Libre de Bruxelles, Brussels, Belgium, and principal
investigator of the study. "The addition of 90Y resin microspheres to systemic
5FU significantly prolonged the time to progression compared with 5FU alone,
more than doubling the interval before disease recurrence in the liver or
anywhere in the body, and was well tolerated by patients who had already
received many previous lines of chemotherapy."

The median time to progression of liver disease - the primary endpoint of the
study - increased from 2.1 months with 5FU alone to 5.5 months with 5FU plus 90Y
resin microspheres (hazard ratio 0.38; 95% confidence interval [CI] 0.20-0.72;
p=0.003) whilst the median time to progression of disease anywhere in the body
was 2.1 vs. 4.6 months, respectively (hazard ratio 0.51; 95% CI 0.28-0.94;
p=0.03). The proportion of patients with disease control following the
combination treatment was also increased significantly from 35% to 85%,
respectively (p=0.001), with one patient (5%) receiving 5FU plus 90Y resin
microspheres having a sufficiently large reduction in tumor size to permit
potentially curative surgical resection of the remaining disease.

All 44 patients in the study had colorectal cancer restricted to the liver, a
median age of 62 (range 45 to 91 years) and had failed or could not tolerate
multiple prior lines of standard-of-care chemotherapy comprising 5FU,
oxaliplatin, irinotecan and available biologic agents.

Following disease progression, 10 patients (43.5%) in the 5FU-only arm
subsequently crossed over to receive 90Y resin microspheres as a salvage
therapy, and so overall survival was extended in both treatment arms by the
targeted treatment of liver tumors. Overall, there was 2.5 months` difference in
the median survival (7.4 versus 9.9 months) between the 5FU and 5FU plus 90Y
resin microspheres arms, respectively (hazard ratio 0.92; p=0.80). Treatment
with 5FU plus 90Y resin microspheres was well tolerated, with significantly more
patients experiencing a serious adverse event in the 5FU-only control arm (4%
vs. 35%, respectively; p=0.02).

"The encouraging results of this randomized trial confirm the findings from
single-arm and retrospective studies of 90Y resin microspheres that have
reported median overall survivals in the order of 10 to 13 months when used
alone as salvage therapy for patients with liver-dominant metastatic colorectal
cancer who have exhausted all chemotherapy options," said Dr Hendlisz.2–4 "Small
randomized controlled trials have also demonstrated significant benefits of
using 90Y resin microspheres earlier in the treatment paradigm and our objective
now is to investigate whether the addition of 90Y resin microspheres to current
first-line standard-of-care chemotherapy could further improve the outcomes for
patients with this disease."5,6

The trial was conducted at the Institut Jules Bordet Université Libre de
Bruxelles, Brussels, Universitair Ziekenhuis Gent, Ghent, and University
Hospitals Leuven, Leuven, with collaboration from clinicians at the Hôpital
Universitaire Erasme in Brussels. The study was supported by Sirtex Medical
through the provision of 90Y resin microspheres and a research grant.

References

1. Van den Eynde M, Hendlisz A, Peeters M et al. Prospective randomized study
comparing intra-arterial injection of yttrium-90 resin microspheres with
protracted IV 5FU continuous infusion versus IV 5FU continuous infusion alone
for patients with liver-limited metastatic colorectal cancer refractory to
standard chemotherapy. 45th ASCO Annual Meeting Proceedings Journal of Clinical
Oncology 2009; 27 (Suppl 7s): Abstract 4096.

2. Cosimelli M, Mancini R, Carpanese L et al. Clinical safety and efficacy of
90yttrium resin microspheres alone in unresectable, heavily pre-treated
colorectal liver metastases: results of a phase II trial. ASCO Annual Meeting
Proceedings Journal of Clinical Oncology 2008; 26 (May 20 Supplement): Abs.
4078.

3. Jakobs TF, Hoffmann RT, Dehm K et al. Hepatic yttrium-90 radioembolization of
chemotherapy-refractory colorectal cancer liver metastases. Journal of Vascular
and Interventional Radiology 2008; 19: 1187-1195.

4. Kennedy A, Coldwell D, Nutting C et al. Resin 90Y-microsphere brachytherapy
for unresectable colorectal metastases: modern USA experience. Int J Radiation
Oncology Biol Phys 2006; 65: 412-425.

5. van Hazel G, Blackwell A, Anderson J et al. Randomised phase 2 trial of
SIR-Spheres plus fluorouracil/ leucovorin chemotherapy versus
fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer.
Journal of Surgical Oncology 2004; 88: 78-85.

6. FOLFOX plus SIR-Spheres microspheres versus FOLFOX Alone in patients with
liver mets from primary colorectal cancer (SIRFLOX).
http://clinicaltrials.gov/ct2/show/NCT00724503

For further information or to arrange interviews, please contact Louise Bannon
at 919-334-3782 or louise.bannon@fleishman.com, on behalf of Sirtex

For Sirtex
Louise Bannon, 919-334-3782
louise.bannon@fleishman.com

Copyright Business Wire 2009