Purpose:SIR-Spheres® are radioactiveyttrium90 microspheres (SIR-Spheres®, Sirtex MedicalLimited, Australia) used to selectively target high levels of ionisingradiation to tumors within the liver. This trial was designed to measureany increased patient benefit by adding a single administration ofSIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC)administered as a 12 day infusion of floxuridine and repeated at monthlyintervals, vs. the same chemotherapy alone.
Patients andmethods:A phase III randomised clinical trial entering 74 patientswas undertaken on patients with bi-lobar non-resectable liver metastasesfrom primary adenocarcinoma of the large bowel. Patient benefit criteriaassessed in the trial were tumor response, time to disease progressionin the liver, overall survival, quality of life, and treatment relatedtoxicity. Tumor response was measured by serial changes in bothcross-sectional tumor areas and total tumor volumes, provided anyresponse lasted not less than three months as well as changes in serumcarcino-embryonic antigen (CEA).
Results:The partialand complete response rate (PR + CR) was significantly greater forpatients receiving SIR-Spheres when measured by tumor areas (44%vs. 17.6%, P= 0.01) tumor volumes (50% vs.24%, P= 0.03) and CEA (72% vs. 47%, P= 0.004).
The median time to disease progression in theliver was significantly longer for patients receiving SIR-Spheres incomparison to patients receiving HAC alone when measured by either tumorareas (9.7 vs. 15.9 months, P= 0.001), tumor volumes (7.6 vs.12.0 months, P= 0.04) or CEA (5.7 vs. 6.7 months, P =0.06).
The one, two, three and five-year survival for patientsreceiving SIR-Spheres was 72%, 39%, 17% and3.5%, compared to 68%, 29%, 6.5% and0% for HAC alone. Cox regression analysis suggests an improvementin survival for patients treated with SIR-Spheres who survive more than15 months (P = 0.06). There was no increase in grade 3–4treatment related toxicity and no loss of quality of life for patientsreceiving SIR-Spheres in comparison to patients receiving HAC alone.
Conclusion:The combination of a single injection ofSIR-Spheres® plus HAC is substantially more effective in increasingtumor responses and progression free survival than the same regimen ofHAC alone.