Tag: Genitourinary Cancer

Prostate Cancer Treatment: Getting the Best Results by Targeting the Right Cells at the Right Time

Lutetium 177 (also known as Lu-177 or 177-Lu) is a very popular radioactive particle used to treat prostate cancer in Europe, as it has previously been shown to be effective against metastatic prostate cancer. For more than 10 years, Weill Cornell Medicine has been one of very few centers in the United States that is able to offer this as a targeted prostate cancer treatment.

Lutetium 177 is a radioactive material that has a short-range, which means that it can act in a targeted fashion against cancer cells with little “collateral” damage to nearby organs and tissues. It needs some help to get to these specific cancer cells though, so we combine it with the J591 monoclonal antibody that binds to a protein expressed on nearly all prostate cancer cells, PSMA. Together, this treatment compound is called 177Lu-J591.

Here’s an overview of how we use monoclonal antibodies to target cancer cells, in this case the target is the prostate cancer tumors:

The treatment approach is called radioimmunotherapy because we’re using a tiny tag of radioactive material that can kill prostate cancer cells (in this case 177Lu) and attaching it to a very specific immune-based courier (J591) to help it get inside these cells.

We already know that 177Lu-J591 can be very effective at eradicating metastatic prostate cancer cells throughout the body. In 2013, we published results from a phase II clinical trial showing that a large, single-dose of this radioimmunotherapy could be safely delivered to patients and that those patients receiving a larger dose had better response and overall survival. This is what’s called a “dose-response.”

While higher doses of 177Lu-J591 are more effective at eradicating the prostate cancer cells, higher doses also increase the likelihood of side effects, including drops in the white blood cell and platelet counts in the blood.

Building on the results of this trial and additional scientific evidence, we hypothesized that by splitting the radiation dose and giving half at the first visit and half two weeks later (a process termed “dose fractionation”) that we would be able to deliver a higher dose of the treatment while minimizing the risk of these side effects.

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Dr. Tagawa presents the clinical trial results at ASCO 2016 in Chicago

Today at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Scott Tagawa presented final results utilizing this split-dosed approach.

The clinical trial showed that the most effective split-dose of 177Lu-J591 was 45 mCi/m2 given in two sessions, two weeks apart, a dose 28% higher than was achievable with a large single-dose. Nearly 90% of the patients in this group experienced a decline in PSA levels, resulting in an average overall survival of more than four years. In addition, the number of circulating tumor cells (also known as CTCs or prostate cancer cells floating in the blood) was decreased or controlled by treatment. In addition to this study, the lower effect of fractionated therapy on blood counts has allowed combination of this therapy with chemotherapy.

This research was supported by the Department of Defense, Prostate Cancer Foundation and the National Institutes of Health.

ASCO 2016 is Upon Us

Each year, more than 30,000 professionals from around the world come together to discuss groundbreaking research findings at the American Society for Clinical Oncology (ASCO) annual meeting.

This year’s meeting, in Chicago from June 3-7, will feature over 5,000 different abstracts. The Genitourinary (GU) Oncology team will be presenting recent prostate and kidney cancer clinical trial results and updates on using precision medicine to translate genomic information into treatments. Vice President Joe Biden will also be at ASCO to deliver remarks on the Cancer Moonshot Initiative to accelerate cancer research and improve patient care through increased collaboration.

Check out the schedule to see when we’ll be presenting, and be on the lookout for daily “What’s New in GU?” blog updates regarding these noteworthy topics and more:

  • The impact of a split-dose schedule using Lutetium 177, a targeted treatment that has been previously shown to be effective against metastatic prostate cancer
  • The effect of changing prostate cancer chemotherapies early on when one drug doesn’t seem to be working as effectively as it could be, and when to switch
  • How a blood test may be used to detect trace tumor cells in the body and what this reveals about the mechanism behind taxane chemotherapy treatment

ASCO 2016

What are Cancer Neoantigens? The Link Between Neoantigens and Immunotherapy

By Bishoy Faltas, M.D.

Our immune system has evolved over time to enable us to fight infections. Our bodies need to differentiate between our own cells (self) and cells from bacteria and viruses (non-self) in order to mount an effective attack to eliminate the invaders. In order to do that, our immune system has learned to recognize fragments of foreign proteins, which carry a specific sequence that marks them as “targets” for the immune system. We call these antigens.

Cancer cells thrive because they hide from the immune system, but their disguise is not perfect. Cells typically become cancerous because of changes in their genetic makeup. These same changes can result in proteins that the immune system is able to recognize as foreign. These are called neoantigens, and refer to new cancer antigens that cue the immune system to attack the cancer and eliminate it.

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New sequencing technologies enable us to detect new cancer antigens unique to each patient.
The immune system just needs a little help to make this happen. To tip the balance in favor of the immune system, we now use drugs called immune checkpoint inhibitors. These unleash the power of the immune system to attack the tumor. A good way to think about it is as “releasing the brakes” off the immune response. This approach to treatment is very promising for bladder cancer, especially when other treatments have failed to stop the cancer from progressing or metastasizing to other organs.

To understand which patients are most likely to respond to these immune checkpoint inhibitors, we conducted a study examining the neoantigens in bladder cancer patients at Weill Cornell Medicine. Our analyses found many differences in the neoantigens between untreated tumors and advanced tumors that had previously been treated with chemotherapy from advanced chemotherapy-resistant bladder cancers. More details on our findings can be found here:

In the future, we are hoping to use neoantigens as biomarkers that tell us which patients are most likely to respond to specific immunotherapies. A form of precision medicine, this will help us to narrowly tailor our treatment approach to each patient.

Some of our current immunotherapy treatments for people with bladder cancers include: