Experts warn of serious side effects of cancer immunotherapies, including lung disease, hormonal disruptions

Cancer immunotherapies, one of the newest agents that are revolutionizing the treatment of cancer, have fewer side effects than conventional cytotoxic anti-cancer drugs. Still, they are not without worrying side effects.

For instance, shortness of breath, dry cough without sputum, and fever could indicate that immuno-oncology drugs should be discontinued.

“Shortness of breath, dry cough without phlegm, and fever can be suspected of interstitial lung disease,” said Professor Sin A-young of the Department of Respiratory Medicine at the Catholic University of Korea Incheon St. Mary's Hospital on a YouTube channel of the Korean Association for Lung Cancer.

“If you have interstitial lung disease, you should consult with your healthcare provider because it is often necessary to stop cancer immunotherapies immediately and use steroids.”

The interstitium is a tissue that includes the capillaries, epithelial cells of the alveoli, endothelial cells, and basement membrane that line the lung sacs (alveoli) walls where oxygen exchange occurs in the lungs. When it is disrupted, it is called interstitial lung disease. The symptoms of interstitial lung disease vary depending on the site and extent of lung involvement.

However, when the disease has progressed to a certain stage, symptoms, including shortness of breath and a dry cough, occur, requiring attention.

Immuno-oncology drugs activate the immune function of the body's immune cells to kill cancer cells and show therapeutic effects. PD-L1, PD-1, and CTLA-4 types of immuno-oncology drugs, including Keytruda, Opdivo, and Tecentriq, are available in Korea.

One of their serious side effects is interstitial lung disease, and encephalitis, hepatitis, colitis, and nephritis may also occur.

If interstitial lung disease is a severe side effect of cancer immunotherapies, the most common adverse reaction from such drugs is endocrine disruption, which is a problem with the “hormones” that regulate the body.

“Hormones are secreted by the pituitary gland, thyroid gland, adrenal gland, and pancreas,” Professor Sin said. “When these organs are affected by immuno-oncology drugs, various symptoms can occur.”

The hormonal disruption caused by immuno-oncology drugs is slightly different depending on which organ is affected. Depending on the symptoms of side effects, cancer patients taking immuno-oncology drugs may need to monitor for endocrine abnormalities.

“Hormonal disruptions in the pituitary gland can cause headaches and vision problems, while side effects in the thyroid gland can cause hyper- or hypothyroidism,” Professor Sin said. “It is important to check for thyroid problems if you are tired more easily than usual, gain or lose weight, or experience chills or constipation.”

She explained that the adrenal glands regulate blood sugar, and when adrenal function is impaired (as a side effect of immuno-oncology drugs), the hormone cortisol is not secreted, which can cause low blood sugar. This can lead to weakness, nausea, vomiting, and loss of appetite.

Side effects of immuno-oncology drugs on the pancreas can lead to diabetes symptoms.

“The pancreas controls the secretion of insulin, and if there is a problem with the function of the pancreas, insulin secretion may decrease, resulting in diabetes, which can cause severe thirst, weight loss, increased urine output, and in severe cases, impaired consciousness,” Sin noted.

Another side effect of injectable immuno-oncology drugs is the “severe infusion reaction” that can occur when they are injected.

“Severe infusion reactions occur when a patient develops chills, tremors, itching, rash, high or low blood pressure, or high or low blood pressure during or 24 hours after receiving immuno-oncology drugs,” Professor Sin said. “Slowing the infusion rate of immuno-oncology drugs or using steroid medications can help control severe infusion reactions.”