Safety and efficacy of repeated anti-CEA radioimmunotherapy (RAIT) with 131I-labetuzumab post salvage resection of colorectal liver metastases

Abstract

14507 Background: As shown recently (JCO 2005; 23:6763–70), a single application of RAIT improved both, median overall survival (OS), and 5-year survival rates of colorectal cancer (CRC) patients (pts) post salvage resection of liver metastases (LM) compared to controls without RAIT (P=0.004). In an ongoing phase II trial we are evaluating the safety and efficacy of repeated RAIT at doses of 2x 40–50 mCi/m2 (3 mos apart) post salvage resection of LM. Methods: To date, 26 pts (8x f, 18x m; age: 63 ± 9 ys) who underwent surgery for CRC-LM have received the first dose of 131I-labetuzumab (Immunomedics, In., NJ, USA), a humanized monoclonal antibody against CEA, within 2 months of LM surgery. Three months after the first RAIT, a second infusion of 40–50 mCi/m2 has been applied to all pts after completion of standardized re-staging procedures. Results: The primary tumor sites were 17 colonic and 9 rectal cancers; primary tumor stages were 5x UICC-II, 7x UICC-III, 14x UICC-IV. 13 pts received adjuvant therapy. In 11 pts preoperative chemotherapy (FOLFOX or FOLFIRI) was given to achieve resectability of bilobular LM. After resection of LM (y)mTNM tumor stages were 1x mTNM-I, 6x mTNM-II, 6x mTNM-III and 4x mTNM-IV, respectively. After first RAIT, hematologic Grade 3 and 4, toxicity (WBC/platelet count) occurred in 8/14 and 5/3 pts, respectively. No cumulative toxicity was seen after repeated RAIT, with complete bone marrow recovery observed in all cases so far. To date, all pts are alive. Of the total, 17 pts received RAIT with adjuvant intention (as classified by FDG-PET and CT scans at pre-RAIT re-staging). In these, DFS was 70% post salvage resection of LM during ongoing follow-up of 15 months (median; range: 4–23 mos). As of Dec. 20, 2006, cancer recurrence was detected in 5/17 pts (3x pulmonary, 1x intrahepatic, 1x both) and in 4 pts R0-resection of distant metastases was done. 1 patient with pulmonary and intrahepatic relapses receives polychemotherapy with palliative intention. The pts‘ compliance to repeated RAIT has been 100%. Conclusion: RAIT re-treatment to date appears to be safe, feasible, and well accepted. Extended follow-up of the encouraging survival data will be presented. No significant financial relationships to disclose.