Novel Human IgG2b/Murine Chimeric Antitenascin Monoclonal Antibody Construct Radiolabeled with 131I and Administered into the Surgically Created Resection Cavity of Patients with Malignant Glioma: Phase I Trial Results

Journal of Nuclear Medicine

Gamal Akabani¹  Jeremy N. Rich¹  Jennifer A. Quinn¹  Sridharan Gururangan¹  Xiao-Guang Zhao¹  David A. Reardon¹  Jeannette M. Dowell¹  Michael R. Zalutsky¹  Annick Desjardins¹  John H. Sampson¹  R. Edward Coleman¹  Roger E. McLendon¹  James E. Herndon¹  Michael A. Badruddoja¹  Charles N. Pegram¹  Henry S. Friedman¹  James J. Vredenburgh¹  Terence Z. Wong¹  Darell D. Bigner¹  Allan H. Friedman¹  James M. Provenzale¹ 

关键词: radioimmunotherapy;    monoclonal antibody;    malignant glioma;    glioblastoma multiforme;    brain neoplasms;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of 131I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. Methods: In this phase I trial, eligible patients received a single injection of 131I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). 131I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after 131I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. Results: We treated 47 patients with 131I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. Conclusion: The MTD of 131I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, 131I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with 131I-murine 81C6.

【 授权许可】

Unknown