Safety and Outcome Measures of First-in-Human Intraperitoneal α Radioimmunotherapy With 212Pb-TCMC-Trastuzumab

Purpose: One-year monitoring of patients receiving intraperitoneal (IP) Pb-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 Pb-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/m) 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 Pb-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 Pb-TCMC-trastuzumab up to 27 MBq/m 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.