Month: December 2022

In June, the FDA approved a new treatment for the most advanced type of prostate cancer. Patients who have this condition, which is called metastatic castration-resistant prostate cancer (mCRPC), have few therapeutic options, so the approval helps to fill an urgent need.

mCRPC sets in when the front-line hormonal therapies that doctors use first for treating metastatic prostate cancer stop working. These drugs limit the body’s production of testosterone, a hormone that fuels prostate cancer growth. If they are no longer effective, then doctors switch to a different class of drugs known as anti-androgens that further inhibit testosterone by blocking its cell receptor. One of those drugs is called enzalutamide.

The newly approved treatment combines enzalutamide with a second drug, talazoparib, that was already on the market for female cancer patients who test positive for BRCA mutations. These inherited gene defects boost risks for breast and ovarian cancer, but they can also elevate risks for prostate cancer in men. Indeed, an estimated 10% of men with metastatic prostate cancer are BRCA-positive.

Talazoparib inhibits a DNA-repair system called PARP that the tumor cells need to keep their own genes in working order. When PARP is blocked by treatment, the cancer cells will eventually die. Other PARP inhibitors, including olaparib and rucaparib, are already approved for advanced prostate cancer in BRCA-positive men.

During research leading to this latest approval, 399 men with mCRPC were randomly divided into two groups. One group received talazoparib plus enzalutamide; the other group was treated with enzalutamide plus placebo. The men averaged 70 years in age, and most of them had already been treated with chemotherapy and/or a different anti-androgen called abiraterone. All the men were positive for either BRCA mutations or defects affecting other DNA-repair genes.

What the study showed

Results from the still-unpublished study were presented at the 2023 American Society of Oncology Annual Meeting in June. After a median follow-up of roughly 17 months, the enzalutamide/talazoparib combination reduced the risk of death or visible signs of tumor progression by 55%.

Among the specific subgroup of BRCA-positive patients, “there was an 80% reduction in risk progression or death, which is enormous for these men and obviously very welcome,” said lead researcher Dr. Karim Fizazi, a professor at the University of Paris-Saclay in France.

Scientists had hoped that combining PARP inhibitors with anti-androgens would similarly benefit prostate cancer patients with no DNA-repair defects, but evidence from a different study by Dr. Fizazi and his colleagues shows they do not.

For that reason, the FDA approved the new combination only for mCRPC patients who test positive for mutations affecting DNA-repair genes. Dr. Fizazi and his colleagues are continuing to monitor the enrolled patients for improvements in other areas, such as overall survival, quality of life, and subsequent need for chemotherapy.

Dr. David Einstein, an assistant professor of medicine at Harvard Medical School and a medical oncologist at Beth Israel Deaconess Medical Center in Boston, says the evidence helps to confirm that PARP inhibitors have a role to play in genetically-selected men with mCRPC. Additional research is needed to assess if the observed benefits are “specific to the combination or just because access to PARP inhibition was provided at some point in the disease course,” he says.

“Genetic testing for BRCA, which originally targeted females, is now becoming mainstream for men with a family history of breast and ovarian cancers, as well as men with mCRPC regardless of family history,” says Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center. “This is important, as it has implications for other family members and treatment choices alike. Also important to note is that where this study enrolled men who had already been treated with chemotherapy and/or abiraterone, future research will likely move the enzalutamide/talazoparib combination — or components of it — to earlier disease stages.”

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. In addition to writing for Harvard Health Publishing, Charlie has written for Science magazine, the Journal of the National Cancer Institute, Environmental Health Perspectives, … See Full Bio View all posts by Charlie Schmidt

About the Reviewer

Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Marc B. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical … See Full Bio View all posts by Marc B. Garnick, MD

Heavy rains and sea level rise contribute to major flooding events that are one effect of climate change. Surging water rushing into buildings often causes immediate harms, such as drowning deaths, injuries sustained while seeking shelter or fleeing, and hypothermia after exposure to cold waters with no shelter or heat.

But long after news trucks leave and public attention moves on, flooding continues to affect communities in visible and less visible ways. Among the less visible threats is a higher risk of respiratory health problems like asthma and allergic reactions. Fortunately, you can take steps to minimize or avoid flooding, or to reduce respiratory health risks after flooding occurs.

How does flooding trigger respiratory health issues?

Flooding may bring water contaminated with toxic chemicals, heavy metals, pesticides, biotoxins, sewage, and water-borne pathogens into buildings. Afterward, some toxic contaminants remain in dried sediments left behind. When disturbed through everyday actions like walking and cleaning, this turns into microscopic airborne dust. Anything in that dried flood sediment — the toxic chemicals, the metals, the biotoxins — is now in the air you breathe into your lungs, potentially affecting your respiratory health.

Buildings needn’t be submerged during flooding to spur respiratory problems. Many homes we studied after Hurricane Ida suffered water intrusion through roofs, windows, and ventilation ducts — and some were more than 100 miles away from coastal regions that bore the brunt of the storm.

The growth of mold can also affect health

Another common hazard is mold, a fungal growth that forms and spreads on damp or decaying organic matter. Indoor mold generally grows due to extensive dampness, and signals a problem with water or moisture. Damp materials inside buildings following a flood create perfect conditions for rapid mold growth.

Mold can be found indoors and outdoors in all climates. It spreads by making tiny spores that float through the air to land in other locations. No indoor space is entirely free from mold spores, but exposure to high concentrations is linked with respiratory complications such as asthma, allergic rhinitis, and sinusitis. Thus, flooding affects respiratory health by increasing the risk of exposure to higher concentrations of mold spores outdoors and indoors.

For example, after Hurricane Katrina in New Orleans in 2005, the average outdoor concentration of mold spores in flooded areas was roughly double that of non-flooded areas, and the highest concentrations of mold spores were measured indoors. A study on the aftermath of Hurricane Katrina and the flooding in the UK in 2007 showed that water damage accelerated mold growth and respiratory allergies.

Children are especially vulnerable to health problems triggered by mold. All respiratory symptoms — including asthma, bronchitis, eye irritation, and cough — occurred more often in homes reporting mold or dampness, according to a study on the respiratory health of young children in 30 Canadian communities. Other research demonstrates that mold contributes to development of asthma in children.

What can you do to protect against the health harms of flooding?

Our research in New Orleans, LA after Hurricane Ida in 2021 identified common factors — both in housing and flooding events — with great impact on respiratory health. Preliminary results suggest two deciding factors in whether substantial indoor mold appeared were the age of a building’s roof and how many precautionary measures people took after flooding from the hurricane. The impact on respiratory health also varied with flood water height, days per week spent at home, and how many precautionary measures were taken after Ida swept through.

Informed by this and other research, we offer the following tips — some to tackle before flooding or heavy rains, and some to take afterward. While you may not be able to entirely prevent flooding from hurricanes or major storms, taking these and other steps can help.

Before seasonal storms, flooding, or heavy rains start: Protect against water intrusion

• Repair the roof, clean gutters, and seal around skylights, vent pipes, and chimneys to prevent leaks. These are some of the most vulnerable components of a building during storms and hurricanes.
• Declutter drains and empty septic tanks.
• Construct barriers and seal cracks in outer walls and around windows, to prevent heavy rain and floodwater from entering.
• Install a sump pump to drain water from the basement, and backflow valves on sewer lines to prevent water from backing up into the home.

After flooding or major rainstorms: Move quickly to reduce dampness and mold growth

The Environmental Protection Agency recommends limiting contact with flood water, which may have electrical hazards and hazardous substances, including raw sewage. Additionally:

• Minimize your stay in flooded regions (particularly after hurricanes) or buildings until they are dry and safe.
• Check building for traces of water intrusion, dampness, and mold growth immediately after flooding.
• Drain floodwater and dispose of remaining sediment.
• Remove affected porous materials. If possible, dry them outdoors under sunlight.
• Increase the ventilation rate by leaving all windows and doors open, or use a large exhaust fan to dry out the building as fast as possible.
• Use dehumidifiers in damp spaces such as basements.
• Upgrade the air filters in your HVAC system to at least MERV 13, or use portable air cleaners with HEPA filters to reduce your exposure to airborne mold spores.

What to do if you spot mold growth

• Wear a well-fitted N95 face mask, gloves, and rubber boots to clean.
• Clean and disinfect anything that has been in contact with water using soap, detergents, and/or antibacterial cleaning products.
• Dispose of moldy materials in sealed heavy-duty plastic bags.

Taking steps like these — before and after a major storm — goes a long way toward protecting your respiratory health.

Read Flooding Brings Deep Trouble in Harvard Medicine magazine to learn more about the health hazards related to floods.

About the Authors

Parham Azimi, PhD, Contributor

Dr. Parham Azimi is a research associate in the department of environmental health at the Harvard T.H. Chan School of Public Health, investigating the indoor environment’s impact on occupant health and wellness and strategies to improve … See Full Bio View all posts by Parham Azimi, PhD

Joseph Allen, DSc, MPH, CIH, Contributor

Dr. Joseph Allen is an associate professor in the department of environmental health at the Harvard T.H. Chan School of Public Health, and the director of Harvard’s Healthy Buildings Program. He is the coauthor of Healthy … See Full Bio View all posts by Joseph Allen, DSc, MPH, CIH