Author: lindseyhemonc

Clotting and Cancer: What’s the Connection?

 

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Image Credit: National Cancer Institute (NCI)

What We Already Know

In the body, there is a tight relationship between cancer development and growth, treatment, and the clotting system. Cancer cells produce substances that “thicken” the blood, so men and women with cancer have a significantly higher risk of developing blood clots. On average, people with cancer are 4-7 times more likely to have blood clots than similar people without cancer. Additionally, patients with cancer being treated for blood clots with traditional anticoagulants have a higher risk of bleeding than patients without cancer.

The importance of this connection is highlighted by a dedicated conference, the International Conference on Thrombosis and Hemostasis Issues in Cancer (ICTHIC). The ICTHIC meeting features educational and scientific presentations on epidemiology, biology, prevention, and treatment of clotting and bleeding related to cancer.

The 8th meeting just took place in Bergamo, Italy. World-renowned clinicians and laboratory scientists once again met and updated colleagues. Highlights included multiple presentations and discussions about risk factors for and treatment of cancer-associated venous thrombosis, blood test-based biomarkers assessing the risk of the development or recurrence of clots, lab studies investigating the mechanisms of the tight relationship between the development, progression, and treatment of cancer and thrombosis, and clinical data regarding the treatment or prevention of blood clots in patients with cancer. Special lectures included Dr. Wolfram Ruf delivering the 4th Simon Karpatkin memorial lecture on “Targeting clotting proteins in cancer therapy” where he described years of research on tissue factors involved in cancer growth and spread (metastasis). Dr. Frederick Rickles described the history of the ICTHIC from its inception in 2001 and how the field has progressed since then with an improvement in both the science in the lab and in the treatment methods and diagnostics used in the patient clinic setting.

What’s New?

Much of this year’s conference focused on venous thromboembolism (VTE), which is most commonly manifested by deep vein thrombosis (DVT = blood clots usually in legs/pelvis) and pulmonary embolism (PE = blood clots in lungs). However, it is now clear that patients with cancer also suffer from a higher rate of arterial thrombosis, meaning that they experience a higher rate of heart attacks and stroke.

In the initial Plenary session on Epidemiology, Dr. Babak Navi, Assistant Professor of Neurology at Weill Cornell Medicine (WCM), presented data on the risk of heart attacks and stroke in women with breast cancer. In collaboration with colleagues at Memorial Sloan Kettering Cancer Center, he used data from a large database of patients with Medicare. This dataset showed that women diagnosed with breast cancer have a higher risk of a heart attack or stroke in the first year after diagnosis compared to similar women without breast cancer.

What We’ve Discovered

This year at ICTHIC, we presented data that followed up on a small pilot study presented at the 7th ICTHIC Meeting in 2014 in which Drs. Choe, Tagawa, and others from WCM’s Meyer Cancer Center and the Englander Institute for Precision Medicine utilized genomic data from men with different types of prostate cancer. Patients with advanced prostate cancer had higher expression of genes involved in coagulation and thrombosis compared to patients with early stage (localized) prostate cancer. Interestingly, patients with NEPC had different gene expression compared to patients with metastatic castration-resistant prostate cancer.

Historically, multiple studies showed that patients with cancer and blood clots had more recurrent clots compared to similar patients without cancer. This led to a change in practice starting in 2003 and now many patients use injectable medications (low molecular weight heparin) as opposed to the traditional oral medications (such as warfarin/Coumadin).

Shortly after this change in best practice, we launched a collaborative study with the University of Southern California, testing one of these injectable low molecular weight heparins (tinzaparin) for the treatment of patients with cancer and blood clots. Part of the study included regular and ongoing blood draws in order to examine the biology of the blood in these patients. In the Plenary session on the treatment of cancer-related blood clots, Dr. Tagawa from WCM and Drs. Piatek, Liebman and others from USC presented the results of this study to a global audience.

The results showed that Tinzaparin performed well when examining recurrent blood clot and bleeding rates. In addition, a blood test at the initial diagnosis of the clot called D-dimer was associated with the chance of a recurrent blood clot 6 months later. The team continues to investigate a number of additional blood test biomarkers from patients with and without blood clots in this study. We hope to be able to identify patients who are most likely to develop a blood clot and for those that do, who is most likely to have recurrence of their blood clot. In the future, this may lead to individualization of the type and/or length of treatment.

What We’re Still Trying to Find Out

WCM and other investigators continue to delve into the problem of neuroendocrine prostate cancer (NEPC), an increasingly common lethal form of the disease. Clinicians dealing with this disease believe that men with this variant of prostate cancer suffer from more blood clots than those with the more common types. However, we still don’t know whether this is related to bulkier tumors, the propensity of treating physicians to use platinum-chemotherapy (which is associated with clots), or underlying disease biology.

In addition to gaining additional insight for individual patients using biomarkers, we are also continuing to develop new drugs for the treatment of clots in patients with cancer. Several new oral agents work in patients without cancer with preliminary data in cancer patients, as well. WCM physicians are joining a global study comparing one of these new oral drugs with the standard injectable medication.

Navigating Dinner When the Food Tastes Worse Than the Plate

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

Food photo_Cancer Taste ChangesSweet, salty, savory and sour are words we often use to describe different flavors in the foods we eat, but cancer and its treatments can turn your sense of taste upside down. It is normal to experience taste changes as a result of cancer and cancer treatment. Some people report a bitter or metallic taste in their mouth, while others find that their overall sense of taste has diminished.

How foods taste and smell can change from day to day, and these changes may affect your appetite. To find foods that are appealing, try experimenting with new foods or cuisines, marinades and spices. It can even help to try new ways of preparing the foods you typically eat. Good oral care is also important.

Here are some tips to help combat common cancer-related taste changes:

Loss of Taste

  • Choose foods with strong and/or tart flavors, such as citrus fruits, vinegar and pickled foods. Marinate meats, chicken and fish to infuse flavor. Try strong flavored greens such as arugula or mizuna greens. Caution: avoid acidic foods if you have a sore mouth or throat.
  • Zinc deficiency can decrease your sense of taste. Discuss testing your zinc level and/or supplementing zinc with your health care provider.

Unpleasant Salty, Bitter, Acidic or Metallic Tastes

  • Add a sweet flavor to foods such as topping salad with fruit. Try topping meats, chicken and fish with a fruit chutney.
  • Use plastic utensils or chopsticks if metal forks and spoons taste unpleasant.
  • Add lemon juice, cucumber slices, cranberries or other flavorings to water.
  • Suck on slices of Granny Smith Apples or frozen chunks of pineapple.

Meat Tastes Strange

  • Choose other protein-rich foods (such as poultry, fish, eggs, dairy products, beans, tofu or soy milk) instead of meat.
  • Marinate and cook meats, poultry and fish in sweet juices, soy sauce, acidic dressings or wine.

Overwhelming Food Odors

  • Choose foods that are served cold, such as sandwiches, crackers and cheese, yogurt and fruit, or cold cereal and milk. Foods served hot often have stronger odors.
  • Carry a handkerchief dabbed with oil that has a pleasant odor such as mint or lavender.
  • Eat in cool, well-ventilated rooms that don’t have any food or cooking odors.
  • Drink oral supplements in a covered cup and with a straw to reduce the odor of the supplement.

Oral Care Tips

  • To keep your mouth clean and healthy, rinse and brush your teeth after meals and before bed (or every four hours during the day).
  • Before eating, rinse your mouth with a solution of 1 quart water, ¾ teaspoon salt, and 1 teaspoon baking soda. This rinse can help keep your mouth clean and improve your sense of taste.

While taste changes can be common during cancer treatment, eating well during treatment can decrease side effects. Good nutrition will help you maintain your weight, your strength, and maximize your quality of life.

If you are struggling with taste changes or any treatment side effects that affect your ability to eat, consult with a Registered Dietitian (RD). Nothing replaces the individualized counseling you will receive from working with an RD on a one-on-one basis. To see a dietitian at the NewYork-Presbyterian Outpatient Nutrition Practice call (212) 746-0838 (physician referral required).

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.