Promising New Radioligand Treatment for Men with Metastatic Prostate Cancer Using Lutetium 177 (177Lu)

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Using small molecules, we are able to target not only the known tumors, but can also treat the unknown tumors.

Physicians and researchers at Weill Cornell Medicine have been utilizing prostate specific membrane antigen (PSMA)-directed radioisotope therapy for more than a decade. Over the years, we have shown that we could use this approach to target the vast majority of prostate cancer tumors (“hitting” essentially all known tumors and avoiding normal organs), demonstrated anti-tumor responses when the J591 antibody is linked to a radioactive particle with a large (single) treatment, and then further improved upon this treatment (while simultaneously reducing the side effects) by dose-fractionation (splitting the dose into two).

Following our lead and with the discovery of new small molecules which also specifically bind to PSMA, European physicians have begun using these compounds tagged with the same radioactive particle. The most common molecule has been termed PSMA-617. They have shown some very nice anti-tumor responses with limited side effects. However, because European laws differ from the U.S., many men are able to pay for treatment outside of the setting of rigorous, organized clinical research studies that clearly define appropriate dosing, efficacy and toxicity.

In January 2017, research was published in the Journal of Nuclear Medicine demonstrating that Lutetium 177 combined with PSMA-617 can reduce the amount of tumors in the body and lead to remission of the cancer as measured by PSA level. Twelve German hospitals reviewed their data and compiled a publication of patients with metastatic prostate cancer who received Lutetium-177 linked to PSMA-617 (177Lu-PSMA-617). Over 18 months, 145 men whose cancer grew despite standard treatments (including abiraterone and/or enzalutamide and chemotherapy) and whose tumors “lit up” on PSMA imaging were treated. While not a proper prospective research study, they were able to determine information about both anti-tumor activity and safety. Most patients who had PSA measured before and after treatment had some decline, with 40% having PSA cut at least in half following a single treatment. Blood counts dropped in less than half (usually to moderate degrees) and some developed dry mouth and/or taste changes. Severe toxicity was rare.

It is encouraging to see that there is a treatment that might lead to reduction in cancer without severe side effects, even in men who previously have received many other lines of treatment. However, both rigorous research as well as access for our patients are current issues. Therefore, we are excited to offer a clinical trial that builds upon our prior experience of anti-PSMA radioimmunotherapy while taking into account the available European data.

This study utilizes the most commonly used molecule, 177Lu-PSMA-617, in a prospective manner. Our prior research has shown that higher doses result in significantly better anti-tumor responses, so one purpose of this study is to perform dose-escalation to determine the safest and most-effective dose without increased side effects. In addition, our research demonstrated that dose-fractionation allowed higher doses with less toxicity, so our treatment schedule will deliver the total dose in 2 fractions.

We look forward to advancing science and also making these treatments available to men in the tri-state area and across the U.S., not just those who can afford to fly to Germany for treatment. At Weill Cornell Medicine and NewYork-Presbyterian, we have an excellent, multidisciplinary team that has led the world in PSMA-targeted radionuclide therapy. We will leverage our combined expertise and experience to translate the exciting knowledge base into true clinical gains for prostate cancer patients.

To learn more about the clinical trial or enroll, click here. Call us at 646-962-2072 to make an appointment or schedule a consultation. 

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