Intraperitoneal radioimmunotherapy (RIT) for desmoplastic small round cell tumor (DSRCT): Initial results from a phase I trial.

Abstract

3033 Background: DSRCT, a rare sarcoma of adolescents and young adults usually arising from the peritoneum, is lethal in >80% of patients despite aggressive multimodality therapy. Recurrences often present as multifocal peritoneal implants, making it uniquely suited for intraperitoneal (IP) targeting. We hypothesized that targeted radiotherapy may improve local control and reduce relapses. IP RIT, by virtue of prolonged residence time and slow transfer to the circulation, may selectively target IP DSRCT while minimizing organ toxicity. The anti-4Ig-B7H3 murine monoclonal antibody 8H9 binds to 96% of primary DSRCT (Med Pediatr Oncol 39:547). 131I-8H9 injected intra-Ommaya is safe (J Neurooncol 97:409). Methods: We initiated a phase I study to test the safety of IP RIT with 131I-8H9. Cohorts of 3-6 patients were treated with 131I-8H9 at escalated doses from 30mCi/m2-60mCi/m2 as a single IP injection. A tracer dose of 2mCi124I-8H9 was given IP before 131I-8H9 to acquire PET images and biodistribution data. Pharmacokinetics (PK) was studied using serial blood draws. Results: 15 heavily prior-treated patients: 13 with DSRCT, 2 with rhabdomyosarcoma received 30, 40, 50mCi/m2 131I-8H9 (3 at each dose level) or 60mCi/m2 (n=6). Dose-limiting toxicity was not seen. Three patients (n=1 each) had transient, self-limiting, possibly therapy-related grade 3 toxicities: neutropenia, hepatic transaminase elevation and thrombocytopenia. No patient required hematopoietic stem cell rescue. Blood half life was 32.5±11.5h (n=12) and mean peritoneal residence time was 14.6h (n=3). Mean absorbed dose to blood based on blood sampling was 0.56±0.21 rad/mCi (n=14). Mean absorbed doses (rad/mCi) to kidney, liver, lung and spleen were 1.72, 1.92, 0.64 and 1.03 respectively (n=3). Dehalogenation was insignificant: >80% iodine remained protein-bound in blood (n=10). 6/7 DSRCT patients treated without evaluable disease remain in remission at a median of 11.1 months post 131I-8H9. Conclusions: IP 131I-8H9 was safe and 124I-8H9 provided valuable PK and dosimetry data. Since maximum tolerated dose was not reached we have expanded patient accrual to a planned dose of 90mCi/m2. Clinical trial information: NCT01099644.