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Stanford University School of Medicine

Researchers investigate new targeted therapy for metastatic prostate cancer

prostatic_adenocarcinoma_with_perineural_invasionMen with localized prostate cancer face good odds: Their relative five-year survival rate is nearly 100 percent. However, men with metastatic disease -- prostate cancer that has spread to another organ like the lungs -- have a relative five-year survival rate of only 29 percent.

Currently, the mainstay treatment for metastatic prostate cancer is hormone therapy, which uses drugs to lower the levels of male sex hormones like testosterone in the body to slow the growth of prostate cancer. Two of the latest hormonal agents, abiraterone acetate and enzalutamide, have shown some improvements in overall survival. Unfortunately, hormone therapy isn't a cure and most patients become resistant to the drugs.

As an alternative, researchers are now investigating more targeted therapies, such as those that seek out prostate specific membrane antigen (PSMA). PSMA is present on the surface of nearly all prostate cancers cells as well as new blood vessels that supply nutrients to cancers, but PSMA is present on only a few healthy tissues in the body -- making it an excellent potential target for drugs that selectively attack tumors while sparing healthy cells.

One such agent is PSMA-617 labeled with the radioactive element lutetium-177, which preferentially binds to PSMA on the surface of prostate cancer cells and delivers a toxic level of radiation to the disease sites.

A group of researchers recently investigated the safety and efficacy of lutetium-177-PSMA-617 for the treatment of metastatic prostate cancer. At 12 centers across Germany, a total of 145 patients, between 43 and 88 years in age, were treated with one to four cycles of the therapy. All the patients had metastatic drug-resistant prostate cancer that was continuing to progress. Receiving lutetium-177-PSMA-617 was their last therapeutic option.

As described in a paper appearing in the January issue of the Journal of Nuclear Medicine, the researchers found that 45 percent of the patients responded positively to lutetium-177-PSMA-617 following all therapy cycles, while 40 percent responded positively after a single cycle. Unfortunately, there were some adverse side effects, such as anemia and dry mouth, but these were considered to be manageable.

Other research groups are also developing alternative PSMA targeted therapies, including researchers at Weill Cornell Medicine who are investigating a targeted radionuclide therapy called lutetium-177-J591.

So far the results have all been modest, but these PSMA targeted therapies may have an important role in treating patients who are resistant to other drug therapies. Further studies are needed to determine the survival benefit of these treatments before they can be approved by the U.S. Food and Drug Administration for clinical use.

Previously: Genomic analysis allows researchers to identify three subtypes of prostate cancer and Patient data shows that common prostate cancer treatment likely doubles risk of dementia
Image of the most common form of prostate cancer by Nephron

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