Safety and Outcome Measures of First-in-Human Intraperitoneal Alpha Radioimmunotherapy with 212Pb-TCMC-Trastuzumab 212Pb-TCMC-Trastuzumab

December 01, 2016

American Journal of Clinical Oncology

Meredith, Ruby F. MD, PhD; Torgue, Julien J. PhD; Rozgaja, Tania A. PhD; Banaga Eileen P. MS; Bunch Patty W. OCN; Alvarez, Ronald D. MD; Straughn, J. Micharl Jr. MD; Dobelbower, Michael C. MD, PhD; Lowy, Andrew M. MD

Abstract

Purpose: One-year monitoring of patients receiving intraperitoneal (IP) 212Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome.

Methods: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of 212Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome.

Results: Six dose levels (7.4, 9.6, 12.6, 16.3, 21.1, 27.4 MBq/m2) were well tolerated with early possibly agent-related adverse events being mild, transient, and not dose dependent. These included asymptomatic, abnormal laboratory values. No late renal, liver, cardiac, or other toxicity was noted up to 1 year. There were no clinical signs or symptoms of an immune response to 212Pb-TCMC-trastuzumab, and assays to detect an immune response to this conjugate were negative for all tested. Tumor marker studies in ovarian cancer patients showed a trend of decreasing Cancer antigen 72-4 (CA 72-4) aka tumor-associated glycoprotein 72 (TAG-72) and tumor growth with increasing administered radioactivity. Other tumor markers, including carbohydrate antigen (CA125), human epididymis protein 4 (HE-4), serum amyloid A (SAA), mesothelin, interleukin-6 (IL-6), and carcinoembryonic antigen (CEA) did not correlate with imaging outcome.

Conclusions: IP 212Pb-TCMC-trastuzumab up to 27 MBq/m2 seems safe for patients with peritoneal carcinomatosis who have failed standard therapies. Serum TAG-72 levels better correlated to imaging changes in ovarian cancer patients than the more common tumor marker, CA125.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

http://journals.lww.com/amjclinicaloncology/Abstract/publishahead/Safety_and_Outcome_Measures_of_First_in_Human.98994.aspx

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