title: Bone marrow recovery and subsequent chemotherapy following radiolabeled anti-prostate-specific membrane antigen monoclonal antibody j591 in men with metastatic castration-resistant prostate cancer.
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 (177)Lu- or (90)Y-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.
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College , New York, NY , USA ; Department of Urology, Weill Cornell Medical College , New York, NY , USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Naveed H
authors.initials: NH
authors.lastname: Akhtar
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nikolopoulou
authors.forename: Gurveen
authors.initials: G
authors.lastname: Kaur
authors.forename: Brian
authors.initials: B
authors.lastname: Robinson
authors.forename: Renee
authors.initials: R
authors.lastname: Kahn
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
keywords: monoclonal antibody; myelotoxicity; prostate cancer; prostate-specific membrane antigen; radioimmunotherapy