Prostate 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 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.
Scott Tagawa, M.D.
Chemotherapy 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Summertime often means vacations and more time outdoors. This also comes with increased exposure to the sun – which isn’t such a “sunny” thing if you’re feeling sensitive to it.
A side effect of chemotherapy that many cancer patients express they feel the most is sun sensitivity. This “photosensitivity” occurs because agents in chemotherapy are radiosensitizers which help to impact treatment, but also increase the body’s sensitivity to UV rays (the radiation from the sun that reaches the earth).
A little bit of sunshine can be beneficial, since the sun provides Vitamin D for strong bones, but too much exposure during chemotherapy can be dangerous and increase your risk of sunburn. Here are 8 tips to protect yourself from the sun’s harmful rays during and after chemotherapy:
- Chemo and the sun don’t get along. Photosensitivity can start immediately after your first treatment and last for a few months post-treatment. Several kinds of medications (for cancer and non-cancer alike) can also increase sun sensitivity; so ask your physician and pharmacist if you’re taking any medications that fall in this category.
- Watch the clock. Avoid mid-day sun exposure when the sun’s rays are most intense. In most places, the sun is the strongest between 10am-4pm.
- Pay to attention SPF. SPF stands for Sun Protection Factor and represents the theoretical amount of time you can stay in the sun without getting burned. It is important to use sunscreens with protection above 30 SPF and to make sure the SPF includes protection against both UVA and UVB rays (labeled as “broad spectrum”). These two different types of rays can both cause sunburn.
- Lather up! Reapply sunscreen every two hours or even more frequently if you’re sweating or swimming.
- Bald is beautiful, but protect your head. Wear a wide-brimmed hat in addition to sunscreen if you have lost your hair, and in general to help protect your ears, neck and face further.
- Stylize with shades. Wear sunglasses with UV protection to protect your eyes any time the sun is out. If your wear prescription eyeglasses, consider getting transitional lenses so that you don’t have to worry about carrying an extra pair.
- Cover-ups are key. Cover your exposed skin as much as possible. Wear long-sleeve shirts and pants so that your body is not directly hit by the sun. Many companies now make sun protective clothing which are light, breathable and offer excellent sun protection without the need for constant re-applying of sunscreen to the covered areas.
- Don’t forget the small spots. Ears, eyelids, feet, and lips can be easily forgotten but need extra protection. Use lip balm with SPF to protect your lips, inquire with your oncologist or dermatologist regarding sunscreens for sensitive areas, and don’t forget to put sunscreen on your ears and top of your feet (two areas that are directly hit by the sun).
In the case of a sunburn, use cold compresses and aloe vera to ease discomfort. Contact your physician if redness persists or if your sunburn is severe.