New Clinical Trial Open for Men with Prostate Cancer

lab-researchProstate cancer grows and spreads via the androgen receptor (AR) pathway. In the beginning of treatment, most men with prostate cancer respond to androgen deprivation therapy (ADT) which cuts off this pathway. Unfortunately, the tumors are smart and evolve to create work-arounds. As a result, most men become resistant to this treatment. We call this later, more evolved form of prostate cancer, castration-resistant prostate cancer (CRPC), as it is molecularly different from the initial tumor.

taxane-figure-with-backgroundTaxane chemotherapies – docetaxel and cabazitazel– are the only treatments to demonstrate a survival benefit in men with CRPC. At Weill Cornell Medicine and NewYork-Presbyterian, we have shown that the mechanism of docetaxel taxane action in prostate cancer is inhibiting the androgen receptor pathway on the cellular level by preventing the cancer cells from being able to communicate with other cancer cells using microtubules. Dr. Scott Tagawa explains our prior research in the below video. This suggests that docetaxel may complement other therapies that target the AR pathway, including hormonal-based therapies such as ADT.

Recent trials of docetaxel plus ADT validated our scientific findings, demonstrating very impressively significant improvement in survival in men with metastatic prostate cancer who had not previously received hormonal therapy (also known as hormone-naïve metastatic prostate cancer). Taken together, these studies in both hormone-naïve and CRPC suggest that combining drugs that independently target AR signaling (what the scientific literature refers to as forming a “vertical pathway blockade”) will be more effective than sequentially using these treatments to combat the spread of the cancer.

Our recently-opened phase I study combines the approved 1st line taxane chemotherapy (docetaxel), approved potent inhibitor of testosterone production (the CYP17 inhibitor abiraterone) and a novel AR signaling inhibitor (apalutamide) in men with chemotherapy-naïve metastatic CRPC.

We hypothesize that combining these three agents that all target the same pathway using different mechanisms will result in a synergy that leads to improved cancer outcomes. We previously reported the safety and initial efficacy results of docetaxel plus abiraterone in a multicenter study. The combination was well tolerated and the preliminary efficacy results were promising, confirming the enthusiasm in the prostate cancer community to explore “early” chemotherapy combined with AR-targeted therapy for mCRPC.

As in all phase I clinical trials, there are two aims to this study. The first will provide safety and preliminary efficacy data on this combination treatment. Additionally, we will be performing molecular analysis of blood/tumor samples to identify biomarkers that are able to help predict which patients are most likely to respond to treatment, as well as to determine why some cancers become resistant to treatment. This would allow us to develop biomarker-driven clinical trials that have the potential to shift the treatment paradigm and improve outcomes for men with advanced PC.

To learn more about this clinical trial or to make an appointment with a physician in the Weill Cornell Genitourinary (GU) Oncology program, please call 646.962.2072.

6 Myths About Chemotherapy

Scott Tagawa, M.D.

dr-scott-tagawaChemotherapy often gets a bad rap due to the perception that the side effects of this cancer treatment are severe. What many people don’t know is chemotherapy refers to an umbrella category for different medications that work in a similar way. Just as different cancers are unique, chemotherapies are also unique and use different formula compounds. They also have brand and generic names.

I want to dispel some of the things I hear from patients about chemotherapy. Here are 6 of the most common chemo myths and misconceptions:

  1. It doesn’t work. False! While new cancer treatments are continuously being researched and developed, chemo remains the treatment gold standard for many types of cancers – including testicular cancer and metastatic prostate and bladder cancers – because it works. Through rigorous research, chemo has been shown to improve survival and increase the cure rates for many cancers, especially genitourinary (GU) cancers. Testicular cancer now has an approximately 99% cure rate which was not possible before chemotherapy. Additionally, chemotherapy increases the cure rates for bladder cancer and was more recently shown to have one of the most significant increases in survival compared to any other prior therapy for prostate cancer. Unfortunately, chemo doesn’t always work on every single type of cancer. In addition to the development of novel therapies, work is ongoing to help us select patients that will have more or less benefit from chemotherapy.
  2. It has significant side effects. This is partially true depending on what type of chemo you’re taking and what you perceive to be a negative side effect. Some chemotherapies cause hair loss as they attack the cancer cells, and this is one of the most “visible” side effects of treatment. What many people don’t realize, however, is that chemo can make patients feel better almost immediately because of its ability to control the cancer. For example, the first chemotherapy approved for prostate cancer (mitoxantrone) was approved because it made men feel better. The next generation chemotherapy (docetaxel) made men feel even better when compared to mitoxantrone. Moreover, the impact chemo has on quality of life is often short-term. Longer term, patients who undergo chemo report feeling better. A recently presented study showed that while overall quality of life was worse at an early time point during chemotherapy, men with metastatic prostate cancer had a superior quality of life a year later. This is likely due to the combination of better long-term cancer control and the fact that most chemo-related side effects are temporary. Additionally, while new treatment options, including immunotherapies, hold promise for many types of cancers, these do not work for everyone and are not without side effects either.
  3. It isn’t a one-size-fits-all approach. There are over 200 types of chemotherapies, each differing in function and specific use. For example, platinum-based chemotherapies are mainly used for bladder cancers while taxanes are used for prostate cancer.
  4. It isn’t a targeted treatment. Chemo is targeted in certain ways because it acts on specific receptors. For example, taxanes, which are one type of chemotherapy agent, have the ability to stop cells from growing by targeting structures inside the cell that help it multiply. In prostate cancer specifically, taxanes kill cancer cells by blocking the movement of specific receptors that promote cancer growth. At Weill Cornell Medicine and NewYork-Presbyterian, we are able to analyze the tumor for genomic mutations that can tell us whether you are more or less likely to respond to this type of treatment.
  5. It is painful. When you are receiving cycles of chemotherapy, it should not hurt. Some patients receive chemo through an IV (intravenously), while other chemos are given as oral medications that you can take at home. Most genitourinary cancer patients undergo treatment on an outpatient basis. If you experience discomfort, burning, or coolness speak to your nurse or another member of your cancer healthcare team.
  6. Chemo suppresses the immune system. I commonly hear this from patients as a reason to avoid chemo. While there is an infection risk associated with chemotherapy if blood counts are low, current data indicates that combining chemo with immunotherapy (either together or sequentially with one followed by the other) may be better than immunotherapy alone.

Oncologists and researchers are always looking for the best treatment options to bring cures to the greatest number of cancer patients. For many patients, chemo remains the best option at controlling the cancer growth and ultimately curing the cancer. For some patients, newer approaches such as immunotherapy or other biologic agents are more tailored to fighting their disease. At Weill Cornell Medicine, we continue to work on identifying which chemotherapy is best for the right tumor in the right patient at the right time, as well as developing strategies to deliver chemotherapy preferentially to tumors (sparing normal organs), and continuing to develop new immunotherapies and biologic-based approaches to treatment.

Moonshot Summit: Changing Cancer As We Know it

DAVID NANUS, MD

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Photo credit: Ira Fox

On June 29, Weill Cornell Medicine and NewYork-Presbyterian Hospital joined more than 270 institutions across the country in holding a Moonshot Summit. These summits were held in conjunction with Vice President Biden’s Moonshot initiative to fight cancer. On this national day of action, cancer experts throughout our institution, survivors, and advocates came together to share their ideas for increased collaboration and cures.

The summit conversation started with a constructive dialogue about clinical trials and the unfortunate fact that for many cancer types, the “standard of care” chemotherapies are not good enough. At Weill Cornell Medicine and NewYork-Presbyterian, immunotherapies and precision medicine are opening new doors in cancer treatment, but sadly not all patients currently have access to these types of cutting-edge treatments.

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A packed room at the Weill Cornell Medicine/NewYork-Presbyterian Hospital Cancer Moonshot Summit (photo credit: Ira Fox)

Clinical trials may have gotten a bad rap in the past, but they are a powerful tool to access innovative treatments. The speakers agreed that clinical trials should be easily accessible to all patients, but at times there are obstacles. These range from lengthy forms that deter enrollment, to bureaucracy that slows the timeline for opening new clinical trials, to disinterest and concerns about the treatments’ effectiveness. On a global scale, there has been a lack of adult participation in cancer clinical trials, while for children we actually see the opposite trend – very high enrollment. What can we learn from this information?

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(L-R) Dr. Gail Roboz and Dr. Susan Pannullo speaking at the Cancer Moonshot Summit (photo credit: Ira Fox)

One of my colleagues Dr. Gail Roboz wisely stated, “I always tell my patients, be afraid of the disease, not the treatment.” She’s right in that we need to reframe the conversation to focus on making strides in increasing cure rates through new research that leads to new treatment breakthroughs across disease states.

We also talked about access to care. Not all patients are able to get a correct diagnosis quickly. This can be due to a variety of reasons including a lack of access to specialists, living in a rural area, or financial limitations. By increasing government research funding, as well as making it easier for patients to reach quality care, we can remove some of these barriers nationally. If we increase the number of people who are diagnosed with cancer early on, we can increase the cure rates. Additionally, as a country, we need to provide comprehensive care for patients and families and always put the interests of patients first. This includes offering supportive services beyond just the best medical care.

I felt so empowered by my colleagues and our patients’ great ideas about how we can overcome the challenges we face in cancer care. The Cancer Moonshot initiative is giving high hopes to many and will help ultimately change the world of cancer care as our country stands together with common goals and a renewed commitment to collaboration. By bringing everyone together at an event like this, we hear diverse perspectives and glean new insights. The fight against this terrible disease truly unites us all.

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Photo credit: Ira Fox