Phase II trial of repeated carcinoembryonic antigen (CEA) radioimmunotherapy (RAIT) with 131I-Labetuzumab post salvage resection of colorectal metastases in the liver

Abstract

13572 Background: Complete resection of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC). As shown recently (Liersch et al., JCO 2005; 23:6763–70), RAIT with a single application of the humanized monoclonal anti-CEA antibody, 131I-labetuzumab, improved both the median overall survival (OS) and 5-yr survival rates significantly in patients post salvage resection of LM. The major adverse side effects (≤ grade 3 CTC) were transient myelosuppression and/or thrombocytopenia in patients receiving 40 to 60 mCi/m2 of 131I-labetuzumab. These encouraging results stimulated the current ongoing Phase-II trial to evaluate the safety of repeated RAIT at doses of 2 × 50 mCi/m2 (3 mos apart), post salvage resection of LM. Methods: At present, 13 patients (primary CRC: 8x UICC stage IV, 1× UICC stage III and 4× UICC stage II) who underwent surgery for LM of CRC (postsalvage mTMN stages: 4× mT4, 2× mT3, 6× mT2, 1× mT1) have received the first dose of 50 mCi/m2 131I-labetuzumab within 2 mos of LM surgery. Three months later, a second infusion of 50 mCi/m2 has already been given to 5 pts. In two, a dose reduction to 40 mCi/m2 was performed. At re-staging CT and PET scans) for the 2nd RAIT, in one patient pulmonary metastases were diagnosed and in another patient a re-resection of hepatic relapse was performed. Results: In the previous trial, at a median follow-up of 67 mos, the median OS from the first liver resection for 19 pts treated with single-dose RAIT was 68.0 mos and median DFS was 18.0 mos. Also, 5-year survival was achieved by 51.3% of RAIT pts independently of bilobar involvement, size and number of LM, or resection margins. In the current study with repeated RAIT, transient grade-4 myelosuppression (2 cases in combination with a myelotoxic thiamazol medication) occurred in 4/13 pts after the first dose (1× grade 4 thrombocytopenia). No cumulative toxicity was seen in 6 of 7 RAIT-re-treated patients. Complete bone marrow recovery was observed in all 6 cases within 5–12 weeks; in one pt severe neutropenia persisted to about week 16 post 2nd RAIT. As of January, 2006, patient compliance was 100%. Conclusion: RAIT re-treatment to-date appears to be safe, feasible, and well accepted. Extended follow-up data are being collected. [Table: see text]