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
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.
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