Researchers Identify Risk Factors of Chemotherapy Side Effect

People being treated with chemotherapy are at risk of developing febrile neutropenia — a dangerously low white blood cell count, which increases their chance of serious infection. Researchers have identified factors related to the risk, according to study findings published in the Journal of the National Comprehensive Cancer Network.

The researchers determined that the timing and length of use for corticosteroids — medications that mimic the effects of the hormone cortisol — influences the likelihood of febrile neutropenia occurring in patients treated with chemotherapy.

“For febrile neutropenia it is important that patients at high risk are managed with prophylactic treatment,” lead author Chun Rebecca Chao, Ph.D., from Kaiser Permanente Southern California Department of Research & Evaluation, said in an interview with CURE. “The consequences (of febrile neutropenia) can be so severe and life-threatening, which requires hospitalization. It can also affect the chemotherapy schedule, which negatively affects the person’s cancer outcome.”

Researchers from Kaiser Permanente Southern California examined 15,971 patients who either had non-Hodgkin lymphoma, breast, lung, colorectal, ovarian or gastric cancer. All patients were treated with chemotherapy between 2000 and 2009. The researchers evaluated the relationship between several suspected risk factors, including radiation therapy; surgery prior to chemotherapy; oral corticosteroid use; oral and IV antibiotic use; and selected dermatologic and mucosal conditions, such as gastritis, dermatitis and psoriasis, and risk of febrile neutropenia.

More than 60 percent of patients had prior surgery and 44 percent had taken oral antibiotics. Radiation therapy was received by 6.6 percent and 2.6 percent of patients in the period prior to and concurrent with chemotherapy, respectively. And oral corticosteroid use was found in 5.6 percent of patients prior to chemotherapy.

During the first chemotherapy cycle, 4.3 percent of patients developed febrile neutropenia. Recent use of corticosteroids was associated with greatest risk of febrile neutropenia, long term use increased the risk further —two and three times the risk, respectively. Similarly, dermatologic and mucosal conditions and IV antibiotics before chemotherapy also proved for higher risk.

“Corticosteroid use is associated with quite higher risk of febrile neutropenia,” Chao said. “Corticosteroids are immunosuppressive drugs, and we know that immunosuppressive drugs are linked to risk of febrile neutropenia, but this study shows that it doesn’t require long-term use of corticosteroids. Even short-term use is still associated with double the risk.”

Preventing febrile neutropenia is crucial because the body’s white blood cells help to fight infection. “When you have low neutrophil counts in the body that means that while a person is on that treatment their body does not have defense against bacterial and fungal infections,” Chao said. “If the count is low enough, they can have very severe infections that can lead to sepsis, which is life-threatening.” The side effect can be treated with IV antibiotics and require a hospital stay until a patient’s counts rise.

It’s best for patients to advocate for themselves and initiate a conversation with their oncologist. “Patients need to understand what the chemotherapy agents do to their disease and also what they do to the rest of the body,” Chao said. “Patients should talk with their physician to choose a regimen that is most beneficial for them in terms of the goal of treating the cancer and managing quality of life.”