UNLABELLED: This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of 90Y-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. METHODS: Fifteen patients received an infusion of 111In-hMN-14 IgG. One to 2 wk later, 14 patients received 90Y-hMN-14 IgG, starting at 740 MBq/m2, followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 mg/m2). Preharvested PBSCs were reinfused when the 90Y activity in the body was < or =111 MBq/m2. RESULTS: The mean red marrow dose estimated for the 90Y-hMN-14 IgG was 1.65 +/- 0.59 mGy/MBq (n = 11), with normal organs ranging from approximately 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 +/- 10.8 mGy/MBq (55.8 +/- 39.8 cGy/mCi) 90Y-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving >2,000 cGy at an administered dose of < or =1,480 MBq/m2. The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 +/- 11.0, 5.1 +/- 3.6, 6.9 +/- 6.1, and 9.0 +/- 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m2. Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). CONCLUSION: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m2. Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.
UNLABELLED: This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of 90Y-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. METHODS: Fifteen patients received an infusion of 111In-hMN-14 IgG. One to 2 wk later, 14 patients received 90Y-hMN-14 IgG, starting at 740 MBq/m2, followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 mg/m2). Preharvested PBSCs were reinfused when the 90Y activity in the body was < or =111 MBq/m2. RESULTS: The mean red marrow dose estimated for the 90Y-hMN-14 IgG was 1.65 +/- 0.59 mGy/MBq (n = 11), with normal organs ranging from approximately 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 +/- 10.8 mGy/MBq (55.8 +/- 39.8 cGy/mCi) 90Y-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving >2,000 cGy at an administered dose of < or =1,480 MBq/m2. The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 +/- 11.0, 5.1 +/- 3.6, 6.9 +/- 6.1, and 9.0 +/- 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m2. Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). CONCLUSION: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m2. Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.
Authors: Robert M Sharkey; Edmund A Rossi; William J McBride; Chien-Hsing Chang; David M Goldenberg Journal: Semin Nucl Med Date: 2010-05 Impact factor: 4.446