Frontiers in Oncology (Aug 2013)

Bone marrow recovery and subsequent chemotherapy following radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 in men with metastatic castration-resistant prostate cancer

  • Scott T Tagawa,
  • Scott T Tagawa,
  • Naveed Hassan Akhtar,
  • Anastasia eNikolopoulou,
  • Gurveen eKaur,
  • Brian eRobinson,
  • Renee eKahn,
  • Shankar eVallabhajosula,
  • Stanley J Goldsmith,
  • David M Nanus,
  • David M Nanus,
  • Neil H Bander

DOI
https://doi.org/10.3389/fonc.2013.00214
Journal volume & issue
Vol. 3

Abstract

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Radioimmunotherapy 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 represents a good candidate for radioimmunotherapy based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen in 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 radioimmunotherapy. Ten subjects underwent bone marrow biopsies at some point in their disease course following radioimmunotherapy for low counts; all had diffuse prostate cancer infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of radioimmunotherapy for men with metastatic castration-resistant prostate cancer. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following radioimmunotherapy.

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