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 /PRNewswire/ -- 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

SOURCE Sirtex