Abstract
Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin’s lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing 177Lu- or 90Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT.
Highlights
It is estimated that in year 2013, approximately 238,590 men will be diagnosed and 29,720 will die due to prostate cancer (PC) in the United States [1]
We have shown that J591 is able to sensitively and target sites of metastatic PC in both bone and soft tissue [28]
RADIOLABELED ANTIBODIES Clinical-grade J591 monoclonal antibodies (mAbs) was covalently linked to the chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) [21]
Summary
It is estimated that in year 2013, approximately 238,590 men will be diagnosed and 29,720 will die due to prostate cancer (PC) in the United States [1]. Despite the effectiveness of hormone therapy, every patient with metastatic disease is currently incurable and those who live long enough eventually progress to castration-resistant prostate cancer (CRPC) [2]. RIT for solid tumors has posed a more difficult challenge for a number of biologic, technical, and practical reasons [6]. Significant progress has been made in the development of RIT for solid tumors. Emphasis is laid on balancing toxicity and therapeutic effects
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