Radioactive resin microspheres delay progression of colorectal
cancer liver metastases
29 June 2009
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) .
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 of Digestive 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
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 tumours.
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
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:
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).
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