A Phase I Trial Combining High-Dose 90Y-Labeled Humanized Anti-CEA Monoclonal Antibody with Doxorubicin and Peripheral Blood Stem Cell Rescue in Advanced Medullary Thyroid Cancer

Journal of Nuclear Medicine

Dion Yeldell¹  David M. Goldenberg¹  Jack Burton¹  Arnold Brenner¹  George Hajjar¹  Arnold Rubin¹  Robert M. Sharkey¹ 

关键词: carcinoembryonic antigen;    medullary thyroid cancer;    radioimmunotherapy;    chemotherapy;    dosimetry;    monoclonal antibody;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 ≤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, 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.

【 授权许可】

Unknown