End-of-Life chemotherapy may do more harm than good

Thursday, July 23, 2015

Dr. Holly Prigerson Treating terminally ill cancer patients with chemotherapy in the months or weeks before their deaths was not found to improve patients' quality of life and may actually do more harm than good, according to a new study led by Weill Cornell Medical College investigators. The findings challenge widespread clinical practice as well as accepted treatment guidelines, and underscore the need for clinicians to reevaluate the common use of chemotherapy at the end of patients' lives, the authors say.

The study found that a majority of the end-stage cancer patients it examined received so-called palliative chemotherapy; oncologists widely assume that in these patients, whose remaining life expectancy is six months or less, that the treatment eases symptoms and extends survival. But this new study, published July 23 in JAMA Oncology, found that it had neither of these effects. Among the patients who at the start of the study were generally healthiest and most active, palliative chemotherapy use was associated with worse quality of life in their last week of life and showed no benefit to overall survival. Those who were less healthy at the study's outset experienced no net effect from the treatment, both in quality of life and survival.

The American Society for Clinical Oncology (ASCO) recommends restricting the use of palliative chemotherapy to highly functioning patients because they are presumed to be most likely to benefit from it. Conversely, ASCO recommends that chemotherapy be avoided in patients who are bed-ridden more than 50 percent of their waking hours, and have reduced or no ability to care for themselves. Routinely giving patients who have been feeling relatively well a palliative treatment that is toxic and can result in side effects is likely to make patients feel worse, not better, said Dr. Holly G. Prigerson, co-director of the Center for Research on End-of-Life Care and the Irving Sherwood Wright Professor in Geriatrics at Weill Cornell.

"This study demonstrates that palliative chemotherapy does not appear to palliate symptoms even in the most robust patients who can tolerate chemotherapy," Dr. Prigerson said. "It raises questions about the rationale for such aggressive, burdensome care."

The current work builds on a previous paper published last year in the British Medical Journal. There, Dr. Prigerson and her colleagues found that people who received palliative chemotherapy were less likely to die at home, more likely to die in an intensive care unit, and more likely to receive aggressive interventions. But that study did not address whether the medicine provided any benefits.

Here, Dr. Prigerson and her colleagues examined 661 end-stage patients — that is, patients with advanced metastatic disease and cancer progression following prior chemotherapy regimens — who were enrolled in their long-term prospective, multi-institutional study. About four months before death, investigators used a scale called the Eastern Cooperative Oncology Group (ECOG) Performance Status to determine patients' health and functioning and whether they were receiving chemotherapy. In interviews conducted a few weeks after each patient's death, their most closely involved caregivers rated their level of psychological and physical distress and overall quality of life in the week before they died.

The researchers found that just over half of the study's subjects were receiving palliative chemotherapy at the beginning of the study. All of the patients with an ECOG score of zero — indicating that they were fully active and had no symptoms or functional impairment — were receiving chemotherapy at that time. Patients with ECOG scores of zero or 1 (meaning they were ambulatory and able to carry out light work) who were receiving chemotherapy at study entry had significantly lower quality of life at the end of their lives than those who were not receiving chemotherapy. Strikingly, among patients with an ECOG score of 1, only 45 percent of those who were receiving chemotherapy had a high quality of life score (seven or above on a 10-point quality of life scale) in the week before death. Among those who were not receiving chemotherapy, 70 percent had a high quality of life score.

"Although we did not find a survival advantage associated with use of chemotherapy, this study was not designed to examine survival. We have proposed further research to examine this explicitly," Dr. Prigerson said. "Nevertheless, these data show that incurable cancer patients with a limited life expectancy who use chemotherapy are likely to impair the quality of their remaining days. Oncologists may presume there to be no harm in giving dying patients chemotherapy, but these data point to more harm than benefit."

Additional coverage in USA Today, New York Times, NPR, the Washington Post, and TIME magazine.