Multi-centre Phase II Trial Reports Safety and Clinical Benefits of Radioactive Microspheres in Patients with Colorectal Cancer Liver Metastases who have Failed Chemotherapy

ROME, August 19, 2010 - Radioactive yttrium-90 labelled resin microspheres (SIR-Spheres; Sirtex
Medical, Sydney, Australia) appear to be a safe and effective treatment for
patients with colorectal cancer liver metastases who have failed available
chemotherapy options, according to the final results of a prospective
clinical multi-centre phase II trial conducted by the Italian Society of
Locoregional Therapies in Oncology (SITILO) and published in the British
Journal of Cancer.[1]

The results of the 52-patient study revealed that the liver tumours
completely disappeared in one patient (2%), and 11 (22%) patients had a
partial response involving at least a 30% reduction in tumour size, which met
the pre-determined criteria for significance (P = 0.05). A further 12 (24%)
patients had stable disease. The liver tumours shrank sufficiently in two
patients (4%) to enable potentially curative surgery to be performed. The
median overall survival was 12.6 months for all patients in the trial, with
significantly longer survival in the 24 (48%) patients that responded to
SIR-Spheres or who had stable disease compared to non-responders (median 16
months versus 8 months; P = 0.0006), and 40% of the responders remaining
alive at two years compared to none of the non-responders. Mild-to-moderate
side effects consisting mostly of fever and pain were reported in 16% of
patients in the first 48 hours and 22% in days 3 to 30.

"These results reveal that radioembolisation using SIR-Spheres is a
promising therapy for patients with colorectal cancer liver metastases who
have failed chemotherapy," said Prof. Maurizio Cosimelli, Professor of
Surgery at the Regina Elena National Cancer Institute in Rome, and
co-ordinator of the study. "The prolonged 12.6-month median survival and
encouraging tumour response reported in the SITILO study compares favourably
with the clinical trial results of second- or third-line chemotherapy, even
though three-quarters of our patients had previously received at least four
different combinations of chemotherapy drugs and therefore had a poor
prognosis with no other treatment options available."

"At a minimum, patients with liver-only or liver-dominant colorectal
cancer who are failing chemotherapy and who remain fit should be considered
for radioembolisation using SIR-Spheres," said Prof. Cosimelli. "However,
SITILO will be conducting a multi-centre randomised trial using SIR-Spheres
in combination with chemotherapy at an earlier line of treatment since we
believe that this may further improve the prognosis for patients with
colorectal liver metastases. Above all, it will be possible to clarify the
potential of SIRT together with chemotherapy to increase the rate of surgical
resections in patients that were previously unresectable."

Patients in the SITILO study had to have liver metastases from colorectal
cancer that could not be removed by surgery and which had progressed despite
modern chemotherapy regimens containing oxaliplatin and irinotecan. The
presence of metastases outside the liver did not exclude the patients from
treatment as long as these were limited in number, size and in the same
organ. All patients were heavily pre-treated, having received at least 3
previous chemotherapy regimens: 24% had received 3 different lines or courses
of chemotherapy, 50% had received 4 lines and 26% had received 5 lines.

The SITILO study used a single-arm design since this group of patients
had no other treatment options available. Patients were reviewed by a
multidisciplinary team of cancer specialists prior to recruitment into the
study. The median survival of metastatic colorectal cancer treated in
clinical studies using modern chemotherapy regimens such as cetuximab plus
irinotecan at second-line and panitumumab at third-line treatment has been
reported to be 8.6 to 10.7 months[2-5] and 6.3 to 9.3 months[6-9]
respectively.

Each year, more than 145,000 Americans and 307,000 Europeans are
diagnosed with colorectal cancer. Around half of these patients will develop
metastases that have spread from the original site of the disease,
predominately to the liver. Up to 90% of these patients ultimately die from
liver failure due to the spread of the disease. Selective Internal Radiation
Therapy (SIRT) using 90Y microsphere therapy is a novel approach to treating
liver metastases. The microspheres are implanted by interventional
radiologists to selectively target the tumors with radiation while sparing
the much-needed healthy liver tissue.

The SITILO study was conducted by a multidisciplinary team of
interventional radiologists, nuclear medicine physicians, medical
oncologists, surgeons and other specialists at the Regina Elena National
Cancer Institute in Rome, the University of Bologna, the University of Udine
and the Cancer Institute of Naples in Italy. SIR-Spheres was developed by,
and is manufactured by, Sirtex Medical, and is the only FDA-approved
microsphere therapy for colorectal cancer liver metastases.

SITILO is the only Italian multidisciplinary oncology society. Different
specialties work together within SITILO to design prospective clinical trials
on loco-regional therapies in the field of liver metastases and primary
carcinoma, melanoma, soft tissue sarcoma, and other cancers. Each protocol
includes a biological component aimed at identifying predictive factors in
serum and tissue.

    The SITILO trial was conducted at the following hospitals:

    - Regina Elena Cancer Institute, Rome, Italy
    - University of Bologna, Bologna, Italy
    - University of Udine, Udine, Italy
    - Fondazione Pascale Cancer Institute, Naples, Italy

    References

    1. Cosimelli M, Golfieri R, Cagol PP et al. Multi-centre phase II
       clinical trial of yttrium-90 resin microspheres alone in unresectable,
       chemotherapy refractory colorectal liver metastases. British Journal
       of Cancer 2010; 103: 324-331.

    2. Sobrero AF et al. EPIC: Phase III trial of cetuximab plus irinotecan
       after fluoropyrimidine and oxaliplatin failure in patients with
       metastatic colorectal cancer. Journal of Clinical Oncology 2008; 26:
       2311-2319.

    3. de Cerqueira Mathias et al. Front cetuximab plus irinotecan in
       patients (pts) with metastatic colorectal cancer (mCRC) progressing
       on or after prior irinotecan therapy: final results of the LABEL study.
       ECCO meeting, European Journal of Cancer Supplements 2007; 5:
       Abs. P3055.

    4. Wilke H et al. Cetuximab plus irinotecan in heavily pretreated
       metastatic colorectal cancer progressing on irinotecan: MABEL study.
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    5. Cunningham D et al. Cetuximab monotherapy and cetuximab plus
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       New England Journal of Medicine 2004; 351: 337-345.

    6. Hecht JR et al. Panitumumab monotherapy in patients with previously
       treated metastatic colorectal cancer. Cancer 2007; 110: 980-988.

    7. Van Cutsem E et al. Open-label phase III trial of panitumumab plus
       best supportive care compared with best supportive care alone in
       patients with chemotherapy-refractory metastatic colorectal cancer.
       Journal of Clinical Oncology 2007; 25: 1658-1664.

    8. Van Cutsem E et al. An open-label, single-arm study assessing safety
       and efficacy of panitumumab in patients with metastatic colorectal
       cancer refractory to standard chemotherapy. Annals of Oncology 2008;
       19: 92-98.

    9. Yoshino T et al. Phase II study of panitumumab (Pmab) monotherapy in
       Japanese patients (pts) with metastatic colorectal cancer (mCRC) after
       the failure of fluoropyrimidine, irinotecan (CPT-11), and oxaliplatin
       (OHP) chemotherapy. ASCO GI Symposium 2008; Abs. 366.

For further information or to arrange interviews, please contact: Prof. Maurizio Cosimelli, Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy, Email: mcosimelli at libero.it; Maya Anaokar at Ruder Finn, Mobile: +44(0)7894-095-429, Email: manaokar at ruderfinn.co.uk