Category: Patient Education

Using Radiation, Radioimmunotherapy and Radioactive Isotopes such as Lutetium 177 to Treat Prostate Cancer

Radiation is a mainstay in the treatment of prostate cancer. In men with localized prostate cancer (confined to the prostate gland), using radiation can help cure the cancer. In men with advanced disease, radiation can improve survival and help to manage pain.

Radiation can be delivered a variety of different ways. For example, there are external beams that can be used to deliver radiation from an external machine into the prostate, radioactive “seeds” that can be implanted, or ways to inject special radioactive isotopes directly into the bloodstream.

In the United States (U.S.), there are older FDA-approved treatments utilizing radioactive isotopes for men with prostate cancer that has spread to the bones to decrease pain, called samarium-153 (brand name Quadramet) and strontium-89 (Metastron). More recently, a bone-targeted alpha particle called radium-223 (brand name Xofigo®) was approved because it leads to longer overall survival in men with symptomatic metastatic castration-resistant bone metastases. These bone-targeted radioisotopes have been useful because prostate cancer commonly spreads to bone. However, those drugs cannot treat other sites of tumors such as in the prostate, lymph nodes, or lung.

We are also able to use parts of the immune system as a way to deliver radioactive particles or other targeted cancer treatments to the prostate cancer. We have engineered very specific monoclonal antibodies and molecules that will bind only to PSMA, leading to the opportunity for “molecularly targeted” radiotherapy for prostate cancer. When we combine immunotherapy with monoclonal antibodies with radioactive isotopes, we call the treatment approach radioimmunotherapy. Radioimmunotherapy involves attaching a radioactive isotope (such as Lutetium 177) to a cancer-targeting antibody or small molecule that binds only to a specific cancer-related molecule on a tumor cell. This is similar to a “lock and key” scenario, where the antibody or molecule serves as a key that will only recognize a very specific lock (the cancer-related molecule). In prostate cancer, nearly all cells have a specific “lock” that lives on the surface of each cell called prostate-specific membrane antigen (PSMA).

j591_psmaFor nearly 15 years, we have been utilizing a monoclonal antibody known as J591, which is a version of a specific key that will only recognize and enter cells with the specific lock PSMA. We successfully utilized this antibody tagged with small radioactive particles to either visualize or treat prostate cancer tumors within the prostate, bone, lymph nodes, and other sites in the body. Our initial studies demonstrated safety and signaled anti-tumor efficacy. In addition, we showed that the antibody went to virtually all sites of tumors (sometimes discovering new ones) and did not target other normal organs (with the exception of the liver which helps clear the drug from the body). Subsequently, our larger studies have shown responses in larger numbers of patients. In Europe, physicians picked up on our results and Lutetium 177 (also known as Lu-177, 177-Lu or 177 Lutetium) has become a very popular radioactive particle that can be directed to prostate cancer via PSMA. It has been used to kill prostate cancer cells and treat hundreds of prostate cancer patients. This commonly-used approach uses a small molecule which recognizes PSMA to deliver Lu-177 to prostate cancer cells (termed radioligand therapy or radioimmunotherapy therapy).

Lutetium-177 PSMA therapy is associated with a good prostate cancer response and many men travel from all over the world to Europe in order to access this treatment. In the U.S. it is only available via clinical trials, and for more than 10 years, Weill Cornell Medicine and NewYork-Presbyterian have been one of the few centers in the U.S. to offer Lutetium 177 and other targeted treatments using radioactive particles.

Learn more about how this treatment works in this video:

Hi-Tech Blood Biomarker Signals When a Strategic Switch in Chemotherapy Will Benefit Prostate Cancer Patients

For men with metastatic prostate cancer that grows despite hormonal therapy (also referred to as castration-resistant prostate cancer), chemotherapy has been a mainstay. The class of chemotherapy that has consistently proved to improve survival for men with advanced prostate cancer is called “taxanes.”

Taxanes target microtubules, which are structures in cells that are involved in cell division, as well as the trafficking of important proteins. In prostate cancer, one of the main ways taxane chemotherapy works to kill the cancer cells involves blocking the movement of the androgen receptor (AR) along the microtubule “tracks” towards the cell nucleus, a mechanism we discovered here at Weill Cornell Medicine.

There are two taxanes FDA-approved to treat prostate cancer, docetaxel (brand name: Taxotere) and cabazitazel (brand name: Jevtana). While the drugs are similar, men whose tumors have grown despite taking one drug often respond to the other. The challenge for oncologists has been pinpointing when exactly to switch treatments.

ScottTagawa_ASCO2016_TAXYNERGYDr. Scott Tagawa presented exciting results from a phase II clinical trial at the 2016 American Society for Clinical Oncology (ASCO) annual meeting demonstrating the power of this treatment switch, and when to make the switch.

This research came to be because we thought that we might be able to increase the number of men who respond to taxane chemotherapy with an early assessment and by changing the drug for those who have a sub-optimal response. Simply put, those with no response or only an initial minor response had their drug changed at a much earlier time point then standard practice. This resulted in a higher response rate for the patients in the study.

Top Boxes_Taxynergy
In the photos from a sub optimally responding patient, almost all of the androgen receptor (AR, labeled in green) is in the nucleus (indicated by the arrow which is overlayed in blue on the right), meaning that the taxane chemotherapy treatment was unable to block AR from moving to the nucleus and thus unable to kill the prostate cancer cells.

In addition, it’s very exciting that we can examine cancer cells from a simple blood test, a process also referred to as collecting circulating tumor cells or CTCs. This allows us to assess the ability of a drug to target the pathway in real time and to tell us whether there is a positive tumor response or resistance.

These circulating tumor cells provide an opportunity for real-time molecular analysis of taxane chemotherapy and at Weill Cornell Medicine we’ve pioneered a way to examine the AR pathway with a simple blood test.

To do this we use an extremely specialized technology that captures the very small fragments or rare circulating tumor cells on a “chip.” From this chip we are able to determine which cells are responding to treatment.

Bottom Boxes_Taxynergy
In real time, we can see taxane chemotherapy kept the (green) AR out of the (blue) nucleus area in cells from a responding patient. 

In cancer care, we are always trying to maximize treatment response rates by targeting the right cells at the right time. This promising precision medicine approach offers us one more tool to better personalize treatment and improve outcomes.

 

Matters of the Bladder: 9 Facts about Bladder Cancer

Bladder_ImageThe bladder is an organ comprised of several layers of cells, and its main job is to store urine. When it’s full, it lets you know. But, chances are there are many other things about the bladder that you may not know. In honor of bladder cancer awareness month in May, here are 9 facts:

  1. There are different types of bladder cancer. Tumors typically form within the different cell layers of the bladder. The name of the specific type of bladder cancer refers to where the cancer started. That’s why bladder cancer is sometimes referred to as urothelial (one of the layers) carcinoma (a fancy word for cancer).
  2. Blood in the urine is a red flag. The most common sign of bladder cancer is blood in the urine (also called hematuria) that can be seen by the naked eye. Usually it is painless. But, bladder cancer isn’t the only culprit for blood in the urine. It can also be caused by an infection or kidney stones. Blood in the urine requires evaluation by a healthcare professional.
  3. It’s common. Bladder cancer is the fifth most commonly diagnosed cancer in the U.S. The National Cancer Institute (NCI) estimates 76,960 new cases of bladder cancer and 16,390 deaths from the disease in 2016.
  4. But lacks funding for research. It is through research that we are able to develop new treatments and ultimately cures. Despite being the fifth most commonly diagnosed cancer in the U.S., bladder cancer ranks 23rd in terms of federal funding.
  5. Some people are at increased risk. Smoking is the greatest risk factor. The good news is you can reduce your risk if you quit. We even have a program to help you get started. Bladder cancer is 3x more common in men than in women, and Caucasians are 2x as likely to develop bladder cancer than African Americans or Hispanics. Risk also increases as you get older and if you have a family history. Visit the Bladder Cancer Advocacy Network to learn more about additional risk factors.
  6. It is diagnosed through different tests. These typically include imaging tests such as ultrasounds, MRIs or CT scans to better see your bladder, urine testing to determine the presence of cancer cells and a biopsy to remove a sample if an area contains cells that appear suspicious.
  7. Treatment will depend on the type of bladder cancer and how advanced and aggressive it is. Treatments vary by stage and include surgery, chemotherapy and immunotherapy.
  8. Immunotherapy offers promise. Immunotherapy is a very encouraging approach for treating bladder cancers and other tumors arising from the renal pelvis and ureters. There are a number of different types currently in clinical trials and the FDA just approved a new treatment called atezolizumab (brand name: Tecentriq). Our team recently presented and published our findings on another form of immunotherapy for bladder cancer, an antibody drug conjugate called IMMU-132.
  9. We are dedicated to and on the forefront of bladder cancer research. At Weill Cornell Medicine, we are committed to research in order to improve outcomes for patients with this disease. The newest member of our Genitourinary Oncology team, Dr. Bishoy Faltas, is dedicated to understanding the genetic makeup of bladder cancer. He’s currently focusing on the genomic changes that happen as the tumors become resistant to chemotherapy. We’re also trying to understand why some patients respond well to immunotherapy, while others do not.