RT Journal Article SR Electronic T1 Safety of First in Human Intraperitoneal Alpha Radioimmunotherapy with 212Pb-TCMC-trastuzumab JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 283 OP 283 VO 56 IS supplement 3 A1 Meredith, Ruby A1 Torgue, Julien A1 Bunch, Patty A1 Fisher, Darrell A1 Alvarez, Ronald A1 Dobelbower, Michael A1 Straughn, John A1 Banaga, Eileen YR 2015 UL http://jnm.snmjournals.org/content/56/supplement_3/283.abstract AB 283 Objectives To determine the long term safety of salvage intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy.Methods 212Pb-TCMC-trastuzumab was delivered IP <4h after 4mg/kg IV trastuzumab. Toxicity monitoring was done for 1 year. Monitoring included clinical findings, laboratory values, cardiac studies and immunologic assays.Results Sixteen patients at five dose levels (7.4, 9.6, 12.6, 16.3, 21.1 MBq/m2) were monitored up to for 1 year (10-11mo for. #14,#15) or until death. There were no clinical signs or symptoms of an immune response, and assays to detect an immune response to 212Pb-TCMC-trastuzumab were negative for all 13 of 16 tested (no sample for 3 patients). Most adverse events were related to disease or medications other than the 212Pb-TCMC-trastuzumab. Patients tolerated therapy at 7-21 MBq/m2 with minimal, asymptomatic laboratory abnormality (transient Grade 1 in 5/16 patients). Whereas hematologic toxicity has been dose-limiting in prior IP radionuclide conjugate studies, the mean platelet counts, total white blood cell counts and neutrophil counts remained normal after a mean equivalent dose to marrow of 0.006cGy/MBq. Only 2 patients had a transient decreased counts to Grade 1(Platelets 142,000/µL, WBC 3500/ µL without neutropenia). No late cardiac, liver or renal toxicity was found.Conclusions Five dose levels of IP 212Pb-TCMC-trastuzumab appear safe for patients with peritoneal carcinomatosis who have failed standard therapies. Monitoring up to 1 year showed minimal, transient toxicity within 6 weeks and no late toxicity.Research Support AREVA Med, and NIH 1UL1RR025777-01