Targeting prostate-specific membrane antigen may benefit men with PCa.


NEW YORK—A radiolabeled antibody against prostate specific membrane antigen (PSMA) may be a useful treatment for metastatic prostate cancer, preliminary findings suggest.

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PSMA is a highly selected prostate-restricted glycoprotein that does not have increased expression in higher-grade tumors, metastatic disease, and hormone refractory prostate cancer (HRPC). PSMA is an ideal target for a monoclonal antibody, according to Matthew I. Milowsky, MD, assistant professor of medicine and urology at Weill Medical College of Cornell University in New York City.


Radio-immunotherapy is an attractive approach for the treatment of prostate cancer, he continued, based on the pattern of metastases to the bone marrow and lymph nodes—sites that receive high levels of circulating antibody as well as a small volume of disease. The antibody, 177Lu-J591 (J591), targets the extracellular domain of PSMA, and the drug can be administered repeatedly.


“This antibody targets the majority of patients with prostate cancer, not just those selected for PSMA. Preliminary phase I and II studies suggest antitumor activity,” Dr. Milowsky stated. Data on 15 patients enrolled in an ongoing Phase II trial suggest that a single dose of the antibody can achieve stable PSA response. One patient achieved a greater than 50% PSA response; four patients had a less than 25% rise in PSA. Response has been durable in some patients. Another 17 patients will enroll in this trial of a single dose of J591.


The principal toxicity of J591 is hematologic, predominantly thrombocytopenia, which is reversible. No non-hematologic toxicity was re-ported; the investigators saw no evidence of immunogenicity. Two phase I trials showed PSA responses, some of them durable, and also soft tissue responses. An ongoing Phase II study is evaluating radiolabeled J591 in more than 100 patients with prostate cancer and 50 patients with other types of cancer.