Randomised phase 2 trial of SIR-Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer

Abstract Purpose Selective internal radiation therapy (SIRT) with SIR‐Spheres® is a new technique for selectively targeting high doses of radiation to tumours within the liver. The primary objectives of this randomised trial were to compare the response rate, time to progressive disease (PD), and toxicity of a regimen of systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a single administration of SIR‐Spheres in patients with advanced colorectal liver metastases. The trial was designed to presage a larger trial that would have survival as the primary outcome. Patients and Methods Twenty‐one patients with previously untreated advanced colorectal liver metastases, with or without extrahepatic metastases, were randomised into the study. Results Using RECIST criteria, the response rate for 11 patients receiving the combination treatment was significantly greater than for 10 patients receiving chemotherapy alone (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD was greater for patients receiving the combination treatment (18.6 months vs. 3.6 months, P < 0.0005). Median survival was significantly longer for patients receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One patient in the combination arm died from chemotherapy induced neutropenic sepsis after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity events in patients receiving the combination treatment. There was no difference in quality‐of‐life over a 3 month period between the two treatments when rated by patients ( P = 0.96) or physicians ( P = 0.98). Conclusions This small phase 2 randomised trial demonstrated that the addition of a single administration of SIR‐Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy significantly increased both treatment related response, time to PD, and survival with acceptable toxicity. The combination of SIR‐Spheres plus systemic chemotherapy is now the subject of ongoing trials to further define patient benefit. J. Surg. Oncol. 2004;88:78–85. © 2004 Wiley‐Liss, Inc.