Sixteen percent of women ages 63 or younger who underwent chemotherapy for breast cancer experienced serious adverse events requiring emergency care or hospitalization, according to a study led by Michael Hassett, MD, at the Dana-Farber Cancer Institute (Boston) and supported by the Agency for Healthcare Research and Quality (AHRQ; Washington).

The study was published Aug. 16 in the Journal of the National Cancer Institute by Oxford University Press.

The authors found that women who received chemotherapy were more likely to be hospitalized for side effects than those who did not receive that treatment. Also, according to the study, “among chemotherapy recipients, incremental expenditure for chemotherapy-related serious adverse effects . . . was $1,271 per person per year.” Ambulatory setting “encounters” were determined to be $17,617 per person per year.

“The study highlights the importance of studying how drugs affect people in everyday medical care,” said AHRQ Director Carolyn Clancy, MD, in a statement. “It is important to know the impact of interventions such as chemotherapy so that patients can make informed decisions about the risks and benefits of the treatment options.”

Most of the adverse events were related to serious complications caused by the toxicity of the drugs, AHRQ said. Those complications included anemia, infection and fever, neutropenia and thrombocytopenia, nausea and diarrhea, dehydration and electrolyte disorders, as well as deep-vein thrombosis or pulmonary embolism.

The researchers employed a database of medical claims made by individuals with employer-provided health insurance between January 1998 and December 2002, identifying 12,239 women in the specific age group of 63 or younger with newly diagnosed breast cancer. Of those, 4.075 received chemotherapy during the 12 months following their initial diagnosis, and 8,164 did not, according to the study.

Of those treated with chemotherapy in the year following diagnosis, the following indicates those who were hospitalized or visited the emergency room during that year: 8.4% for fever or infection; 5.5% for neutropenia or thrombocytopenia; 2.5% for dehydration or electrolyte disorders; 2.4% for nausea, emesis or diarrhea; 2.2% for anemia; 2% for constitutional symptoms; 1.2% for deep vein thrombosis or pulmonary embolus; and 0.9% for malnutrition.

The researchers said that data from their population-based sample suggest that at least 35,000 women under the age of 64 receive chemotherapy for breast cancer every year in the U.S.

“If this estimate is correct, then incremental expenditures for hospitalization or emergency room visits due to chemotherapy-related serious adverse events could reach $45 million per year,” the researchers wrote.

The authors wrote that “although large clinical trials of adjuvant chemotherapy for breast cancer have reported that hospitalizations for serious adverse events are uncommon,” only one other study by the National Cancer Institute (NCI; Bethesda, Maryland) had investigated this and found that “in a . . . [study] linked with Medicare claims data found that, for women with breast cancer who were treated in actual practice, the rates of hospitalization for eight chemotherapy-related toxicities were higher than had been expected based on results of large clinical trials.”

The study authors also said that “healthcare providers must carefully decide whether [large clinical] trial results can be applied to routine clinical practice,” because [Hassett's and his co-researchers'] “results suggest that breast cancer chemotherapy may cause more patient suffering and higher healthcare costs than previously estimated.”

In an accompanying editorial in the Journal of the National Cancer Institute titled “On the Toxicity of Chemotherapy for Breast Cancer – the Need for Vigilance,” authors John Erban and Joseph Lau, MD, of the Institute for Clinical Research and Health Policy Studies at Tufts-New England Medical Center (Boston), noted that the Hassett study was the “first to assess toxicities in a younger population of breast cancer patients.”

Erban and Lau also noted that “First, do no harm” is a “central tenet guiding medical practice.”

Saying that clinicians depend on “well-designed trials” for important treatment guidelines, the writers said, “clinical trials in cancer are usually powered to assess endpoints such as disease-free and overall survival, rather than the toxicities of interventions.

“Furthermore, even in well-designed trials, toxicity reporting is often incomplete, uncertain or truncated at the reporting of the primary endpoint,” Erban and Lau wrote.

While they did raise certain questions about the Hassett study's methodology, they wrote that “there are several important messages implicit in this article.”

“One is the need to continue to develop patient-specific predictive instruments to focus the use of therapeutic drugs and the supportive treatments that accompany the drug therapies,” they wrote.

Erban and Lau added, “As therapy becomes increasingly tailored to individuals, population-based recommendations will become less widely used, and thus, the potential for indiscriminate toxicity will be reduced.”

They also warned that perhaps the “most important message” from the study is that as medicine enters the “new era of targeted therapies, we must be especially vigilant for the potential of late adverse effects.”