Quality of life takes a hit in healthiest cancer patients, researchers say.

By Charles Bankhead, Staff Writer, Medpage Today

Chemotherapy near death failed to improve quality of life (QOL) for patients with cancer, even those who otherwise were in good health, a review of end-of-life care showed.

Quality of life near death (QOD) deteriorated in patients who had good performance status when they started chemotherapy. Palliative chemotherapy had no impact on QOL among sicker patients, Holly Prigerson, PhD, of Weill Cornell Medical College in New York City, and colleagues reported online in JAMA Oncol

“Results indicated that the association between chemotherapy use and worse QOL in the final week of life for patients with good perfromance status at the time of enrollment remained statistically significant even after adjustment for receipt of aggressive life-prolonging care,” the authors said. “Thus, chemotherapy appears to contribute directly to worse QOD, presumably through adverse and toxic effects that impair the QOL of those who are initially feelling well.”

Organizations that have clinical guidelines addressing end-of-life chemotherapy, such as the American Society of Clinical Oncology (ASCO), might need to rethink their recommendations, Prigerson and colleagues added.

However, the authors of an accompanying editorial disagreed.

“At this time, it would not be fitting to suggest guidelines must be changed to prohibit chemotherapy for all patients near death without irrefutable data defining who might actually benefit,” said Charles D. Blanke, MD, and Erik K. Fromme, MD, of Oregon Health & Science University in Portland.

Blanke and Fromme acknowledged that “if an oncologist suspects the death of a patient in the next 6 months, the default should be no active treatment.”

Little Evidence of Benefit

Despite lack of data to document a beneficial effect, many patients with end-stage cancer receive palliative chemotherapy near the end of life. For example, a study of patients with advanced non-small cell lung cancer (NSCLC) showed that 28% had bad or poor performance status, but 40% of them received chemotherapy. Prigerson and colleagues pointed out that third-line chemotherapy for NSCLC has a 2% overall response rate, declining to 0% for fourth line.

Three years ago, ASCO’s expert panel for the “Choosing Wisely” campaign identified use of chemotherapy in patients for whom no proven benefit existed as one of the most widespread, wasteful, and unnecessary practices in oncology. ASCO recommends against the use of chemotherapy for patients who have not benefited from prior therapy and who have an Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (bad or more debilitated).

Prigerson and colleagues examined the association among ECOG performance status, chemotherapy, and QOL in the last week of life (QOD). They hypothesized that patients with good performance status would have worse QOL if they received additional chemotherapy, and that patients with poor performance status would not have an improvement in QOL with chemotherapy.

Investigators in the multicenter study recruited 312 patients with end-stage cancer treated from September 2002 to February 2008. ECOG performance status and chemotherapy use were determined at enrollment, which occurred at a median duration of 3.8 months before death.

Key Findings

By multivariate analysis, factors independently associated with chemotherapy use were age (OR 0.96), baseline performance status (OR 0.67), academic center (versus community clinic, OR 17.1), hospital (versus community clinic, OR 4.07), and disease (pancreatic, breast versus other cancers, OR 4.17, OR 2.45, respectively).

Chemotherapy did not significantly affect survival (OR 0.85, 95% CI 0.65-1.11). Analysis by ECOG stratum did not change the results, even after adjustment for enrollment site.

Baseline performance status significantly modified the association between chemotherapy use and QOD (OR 1.95, 95% CI 1.13-3.35).

Further analysis showed that patients with baseline ECOG performance status 1 had significant deterioration of QOD with chemotherapy (OR 0.35, 95% CI 0.17-0.75) and a lower mean score for continuous QOD measure (6.0 versus 7.0 for the nonchemotherapy group, 95% CI -1.9 to -0.1). The association between chemotherapy and worse QOD remained significant after controlling for receipt of intensive care (such as ventilation or resuscitation) in the last week of life (P<0.01).

Receipt of chemotherapy did not significantly alter QOD for patients with baseline ECOG performance status of 2 or 3.

“Consistent with ASCO guidelines, patients with good performance status were the ones most likely to receive chemotherapy near the end of life,” the authors noted. “However, patients receiving palliative chemotherapy with an ECOG performance status of 0 or 1 had significantly worese QOD than those who avoided chemotherapy.”

“Given no observed survival benefit in the studied patients with refractory metastatic disease and the observed significant association between chemotherapy use and worse QOL in the final week of life among those with a baseline ECOG store of 1, these results highlight the potential harm of chemotherapy in patients with metastatic cancer toward the end of lilfe, even in patients with good performance status,” they added.

The study had some limitations including a lack of information on the dose and duration of the chemotherapy used. Also, patients were not randomly assigned to a chemotherapy arm. Finally, the authors pointed out that “no minimally important difference has been validated for our QOL measure.”

Treatment Versus Hope

Beyond the data, the study suggests that “equating treatment with hope is inappropriate,” Blanke and Fromme said.

“Even when oncologists communicate clearly about prognosis and are honest about the limitations of treatment, many patients feel immense pressure to continue treatment,” they said. “Patients with end-stage cancer are encouraged by friends and family to keep fighting, but the battle analogy itself can portray the dying patient as a loser and should be discouraged. Costs aside, we fell the last 6 months of life are not best spent in an oncology traetment unit or at home suffering the toxic effects of largely ineffectual therapies for the majority of patients.”

In response to a request for comment, ASCO referred to its statement on care of patients with advanced cancer. The statement emphasizes individualized treatment plans and frank conversations between patients and clinicians about treatment options, choices, and limitations.

“This is a clarion call for oncologists as individual practitioners, and for our profession in general, to take the lead in curtailing the use of ineffective therapy and ensuring a focus on palliative care and relief of symptoms throughout the course of illness,” authors of the ASCO statement concluded.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner