Yttrium Y 90 monoclonal antibody MN-14(NCI)

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 i.v. bolus dose of doxorubicin (60 mg/m²).Preharvested PBSCs were reinfused when the ⁹⁰Y activity in the body was ≤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 ∼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 ≤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, resp.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 nonhematol. 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.