科研之友
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摘要
Objective: The aim of this study was to test the hypothesis that adjuvant radioimmunotherapy (RIT) prevents recurrent liver metastases and/or results in improved survival after tumorectomy in an experimental model.
Background: Although partial hepatectomy can improve 5-year survival of patients with colorectal liver metastases up to 58%, recurrent tumor growth in the liver occurs frequently. Radioimmunotherapy using radiolabeled monoclonal antibodies directed against tumor-associated antigens is considered most suited for treating minimal residual disease and could therefore serve as an adjuvant after surgery.
Methods: Liver metastases were induced in male Wag/Rij rats by a minilaparotomy with intrahepatic injection of 0.3 x 10(6) CC531 tumor cells. The biodistribution of the radiolabeled monoclonal antibody MG1, directed against a 80-kDa cell surface antigen on CC531 tumors, in this model was determined at 1, 3, and 7 days after intravenous administration. The therapeutic efficacy of (177)Lu-MG1 was compared with that of a sham antibody (UPC10), labeled with the same activity dose of Lu-177, and saline only. Radioimmunotherapy was administered either at the day of the tumorectomy (day 14 after tumor cell inoculation) or 7 days later. Primary endpoint was survival.
Results: Radiolabeled MG1 preferentially accumulated in tumor lesions in the liver reaching a maximum 3 days postinjection (8.7 +/- 0.6% injected dose per gram). Both the administration (177)Lu-MG1 and (177)Lu-UPC10 resulted in a transient decrease in body weight. No other signs of clinical discomfort were registered. The survival curves of the group that received (177)Lu-UPC10 and the group that received saline only did not differ (P=0.886). Administration of RIT immediately after surgery improved survival compared to administration of the control antibody (hazard ratio [HR], 1.54; P = 0.051), which was even more pronounced when survival was adjusted for the weight of the resected tumor (HR, 1.71; P = 0.027). A therapeutic efficacy of delayed treatment seemed likely (HR, 2.34; P = 0.055). Survival after early administration did not differ from delayed administration (HR, 1.16; P = 0.763).
Conclusion: This study provides proof of principle that RIT can be an effective adjuvant treatment modality after surgical treatment of colorectal liver metastases.
- 出版日期2011-2
