Chemo and Prostate Cancer: Not All Treatments (or Cancers) are Created Equal

By Scott Tagawa, M.D.

In casual conversations, chemotherapy is often referred to as one type of cancer treatment, but it actually refers to different classes of drugs/medications that work via a similar mechanism.

Taxanes are the only class of cheTagawa_Prostate Cancer_Chemotherapymotherapy agents that have significantly improved survival in men with advanced prostate cancer. These include docetaxel (Taxotere ®) and cabazitaxel (Jevtana ®). Though there have been exciting advances in hormonal therapies, bone-targeted therapies, and immunotherapies that have led to a multitude of FDA-approved therapies for patients, chemotherapy is a mainstay.

Chemotherapy was initially approved because men with advanced prostate cancer felt better and in less pain after receiving it. In 2004, docetaxel chemotherapy was approved because it made men feel even better than the older chemotherapy and it also controlled the prostate cancer well enough to lead to longer lifespan. However, the use of chemotherapy was initially limited due to fears of side effects and since 2011, additional medicines have been approved.

The recent success in large clinical trials using taxane chemotherapy has demonstrated unprecedented survival advantages when these drugs are used early. The CHAARTED and STAMPEDE trials showed a much larger improvement in survival compared to any treatment that has been studied in the modern era. Additional trials of men with earlier stages of prostate cancer have also pointed towards patient benefit. However, not all men respond to this treatment and despite improvements in quality of life for symptomatic men with advanced cancer, side-effects do exist. As a result, there is interest in identifying markers that can more accurately identify patients who will respond to this treatment and those for whom taxane chemotherapy is less likely to work. Many efforts are already in the works and progress has already been made.

A genetic alteration known as TMPRSS2-ERG that was co-discovered by Weill Cornell Medicine (WCM)’s Dr. Mark Rubin, Director of the Caryl and Israel Englander Institute for Precision Medicine, is unique to prostate cancer and present in tumors in about 50% of men with prostate cancer. Interestingly, we later discovered that the protein created by this gene fusion called ERG binds to tubulin, which is the molecular target of taxane chemotherapy.

Because of this protein’s interaction with tubulin, there is interference with the “drug-target engagement” of taxanes, leading to resistance. With this scientific discovery, in addition to outlining the mechanism and demonstrating drug-resistance in lab experiments, WCM investigators in collaboration with a group in Sydney tested tumors from human patients that received docetaxel chemotherapy. In this small group of men, those whose tumors expressed ERG were less likely to respond to docetaxel.

In a recent publication, Spanish investigators built on this discovery and identified TMPRSS2-ERG as a biomarker present in the bloodstream, making it a potentially easy way to use a blood test to predict resistance to taxane chemotherapy. This group of scientists from Barcelona used a blood test in men with advanced prostate cancer prior to starting docetaxel or cabazitaxel chemotherapy to determine the presence of TMPRSS2-ERG. Their work confirmed that men with tumors harbouring the gene fusion have resistance to this type of chemotherapy.

Though additional research is ongoing (and needed), there are now a number of treatment choices available. In the near future, physicians might be able to pick the drug that is most likely to work on an individualized basis, perhaps even through a simple blood test. This is another step towards our goal of precision medicine: the right treatment for the right patient at the right time.

Weighty Matters: The Kidney Cancer-Obesity Connection

By Shayne Robinson, R.D., C.S.O, C.D.N

In March, we celebrate both National Nutrition Month and Kidney Cancer Awareness Month. This makes it the perfect time to talk about whether what we eat can play a role in preventing kidney cancer.

So is there a connection between diet, exercise and kidney cancer?

The World Cancer Research Fund International Continuous Update Project seeks to find out. They analyze global cancer prevention and survival research linked to diet, nutrition, physical activity and weight to determine whether certain lifestyle factors affect cancer risk. They then release reports based on the evaluation of this worldwide data.

Map Kidney Cancer Obesity
Image credit: American Institute for Cancer Research, aicr.org

When it comes to the kidneys, there is strong evidence that being overweight or obese increases the risk of developing kidney cancer. In fact, the latest findings showed that maintaining a healthy weight could prevent 24% of all kidney cancers in the United States. The report also found that there was an association between body fatness and kidney cancer, such that the more overweight people were, the greater their risk of developing kidney cancer. Being overweight or obese was assessed by body mass index (BMI), waist circumference and waist-to-hip ratio.

The good news is that this means that we can make healthy lifestyle changes to lose weight and reduce our risk of developing kidney cancer.

Wondering if you should lose weight?

See where you stack up on a BMI chart and measure your waist circumference. To measure waist circumference, place a tape measure around your waist above the tip of your hipbone. Measure your waist after exhaling. For women, a waist measurement of 31.5 inches or more indicates high risk for obesity. For men, a waist measurement of 37 inches or more indicates high risk for obesity. If your BMI is over 25 or your waist circumference is above these numbers, talk to your physician or Registered Dietitian about starting a weight loss program.

Here are 6 tips to get started with a weight loss plan:

  1. Lose pounds the healthy way. Move more and eat less. Avoid fad diets.
  2. Avoid high calorie, energy-dense beverages. This includes fruit juice, soda, sweetened coffee beverages, lemonade and sweetened tea. These beverages don’t provide the satiety you will get from eating solid foods.
  3. Eat your veggies! Cut back on energy-dense, high-calorie foods by making half your plate raw or steamed, non-starchy vegetables. These high-fiber vegetables will fill you up without weighing you down.
  4. Portion control is key. Scale back on portion sizes, except the non-starchy vegetables. Using smaller plates can help.
  5. Get movin’ — Increase your physical activity. For some people, this may mean starting by walking to the mailbox and back. Aim for 30 minutes of physical activity a day. If you can’t do 30 minutes, start small and increase as your fitness improves.
  6. See a professional. Nothing replaces the individualized counseling you will receive from working with a registered dietitian (RD). To see a dietitian at the NewYork-Presbyterian Outpatient Nutrition Practice call (212) 746-0838. A physician referral is required.

Living with One Kidney? 5 Things to Know

Dr. Molina and Dan R.
With many types of kidney cancer, surgical removal of the cancerous part of the kidney is part of treatment. This is also known as a “nephrectomy.” Depending on the size and location of your tumor, you may have had all or part of the kidney removed. People only need one kidney, but it’s very important to protect your remaining kidney function since the kidneys are responsible for filtering your blood and removing wastes from your body.

March is Kidney Cancer Awareness Month and the second Thursday in March is World Kidney Day. After you’ve had all or part of your kidney resected in order to remove a tumor, there are certain things to keep in mind in order to preserve your remaining kidney function. Here are five things you should know:

  1. Certain medications may need to be adjusted or avoided. Medications should be dosed according to your level of remaining kidney function. This is called “renal dosing” and pertains to all medications filtered by the kidneys (which covers a diverse group ranging from certain medications for cholesterol, heart disease, blood pressure, diabetes, infections and pain). A medical oncologist who specializes in kidney cancer should take this into account when prescribing medications, including dosing for cancer treatments. Some over-the-counter drugs are also “nephro-toxic” or harmful to the kidneys. These include non-steroidal anti-inflammatory drugs (NSAIDs), a type of pain medication that includes ibuprofen (Advil®), aspirin and naproxen (Aleve®).
  2. Speak up before imaging tests. Certain imaging tests that might be necessary to see what’s going on in your body and determine whether your cancer has spread, require the injection of contrast dyes. It’s critical to tell the imaging technician that you only have one kidney before undergoing these tests or any procedures. You should also hydrate before and after the test, and you may need to stop taking certain medications beforehand, such as metformin for diabetes. It’s important to discuss your specific situation with your healthcare team before you undergo any procedures.
  3. Drink up! Drinking plenty of water and staying hydrated is important on an ongoing basis, not just when undergoing imaging tests. Being hydrated helps your kidneys filter the wastes and toxins out of your blood so that they can leave your body as urine. Aim for your urine to be clear or pale yellow. Staying hydrated also helps prevent kidney stones.
  4. Watch the sugar and hold the salt. Diabetes and high blood pressure can damage the kidneys, so it’s important to monitor your sugar and salt/sodium intake. People with only one kidney should consume less than 2300mg sodium each day. This is approximately one teaspoon of salt. Those with diabetes should regularly check blood sugar levels. Additionally, maintaining a healthy weight and incorporating physical activity can help prevent developing type II diabetes.
  5. Know your numbers. There are certain blood and urine tests that you’ll want to monitor for changes in your level of kidney function over time. These include your estimated glomerular filtration rate (eGFR) which indicates how well your kidneys are filtering the wastes from your blood, the albumin to creatinine (A:C) ratio which indicates the level of protein in your urine, as well as tests for blood and infection. Work with your primary care physician to make sure you’re receiving these tests on an annual basis and you should see a nephrologist (kidney function specialist) if your eGFR is less than 30 milliliters per minute (ml/min) or if you have large amounts of blood or protein in the urine.