Palliative Chemo Worsens Quality of Life in Dying Patients

Roxanne Nelson, BSN, RN

July 23, 2015

Patients with end-stage cancer often receive chemotherapy, under the assumption that it will improve their quality of life or may even extend survival. However, new data suggest quite the opposite.

The new findings come from a study involving 661 patients with progressive metastatic cancer, of whom about half (n = 312) received at least one dose of chemotherapy as a palliative treatment. The investigators found that chemotherapy did not improve quality of life and, in fact, made it worse. There was also no benefit to overall survival.

The study was published online July 23 in JAMA Oncology.

"It's important to understand why oncologists are prescribing chemotherapy to patients who are at such an advanced stage of their illness and who have proven refractory to chemotherapy in the past," said lead author Holly G. Prigerson, PhD, codirector of the Center for Research on End-of-Life Care and the Irving Sherwood Wright Professor in Geriatrics at Weill Cornell Medical College, New York City. "If this so-called palliative chemotherapy is given to improve their symptoms, then these data should give them pause that it's not going to help."

The findings indicate that patients with good performance status were the ones most likely to receive chemotherapy near the end of life, she said in an interview.

"In our study, 100% of the patients who were feeling well and asymptomatic were being given chemotherapy," Dr Prigerson explained. "So the question is, why? Why would a person who was functioning well be given chemotherapy?"

 
Why would a person who was functioning well be given chemotherapy? Dr Holly Prigerson
 

It may be that it was given to try to reduce the spread of the cancer, she speculated. "However, these were patients with a life expectancy of less than 6 months, and the irony is that because they are doing well, oncologists feel that they are the ones who may benefit most, when in fact these patients have the most to lose by getting chemotherapy," she said.

"It is disturbing that this trial demonstrated no benefits of chemotherapy for patients with solid tumors or poor prognosis, and it is disconcerting that oncologists still recommend and use systemic therapy so close to patient death," two experts write in a related commentary.

Charles D. Blanke, MD, and Erik. K. Fromme, MD, both from the Oregon Health and Science University, Portland, consider what message this study holds for clinical practice.

"If an oncologist suspects the death of a patient in the next 6 months, the default should be no active treatment," they suggest. "Let us help patients with metastatic cancer make good decisions at this sad, but often inevitable, stage. Let us not contribute to the suffering that cancer, and often associated therapy, brings, particularly at the end."

Chemo Use Common Despite Guidelines

Despite the lack of evidence to support the practice, chemotherapy is widely used in cancer patients with poor performance status and progression following an initial course of palliative chemotherapy, the authors note.

"ASCO guidelines say to limit the use of nonessential chemotherapy," Dr Prigerson pointed out, "and especially in those with a poor performance status. But here we see that the people who are the most likely to tolerate it are the ones who are most harmed, because they feel well initially, and then they end up feeling worse."

"We've found that many of these patients have failed multiple lines of chemotherapy, so the likelihood that the tumor will respond is very questionable and unlikely," she explained. "The rationale is that the chemotherapy will shrink the tumor, the cancer won't spread, they'll live longer and feel better, but the dots don't connect that way."

Patients getting palliative chemotherapy may also be more likely to receive aggressive care at the end of life. As previously reported by Medscape Medical News, a study published last year in the BMJ found that patients who received palliative chemotherapy in their final months of life had significantly higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life, compared with those who did not (14% vs 2%; adjusted risk difference [ARD], 10.5%).

Late hospice referrals were also higher (54% vs 37%; ARD, 13.6%).

In addition, those who received palliative chemotherapy were significantly more likely to die in an intensive care unit (11% vs 2%; ARD, 6.1%) and less likely to die at home (47% vs 66%; ARD, -10.8%).

Worsened Quality of Life

In the current article, Dr Prigerson and her team conducted a longitudinal cohort study of 661 patients with end-stage cancer between September 2002 and February 2008. The 312 patients who received at least one chemotherapy regimen were followed prospectively until their death.

The researchers report that the patients who received chemotherapy tended to be younger (56.3 years vs 61.0 years; P = .001), better educated (13.1 years vs 11.6 years; P = .001), had lower comorbidity scores (Charlson Comorbidity Index, 8.3 vs 9.0, P = .02), better performance scores (ECOG, 1.6 vs 2.0; P < .001), and were more likely to be recruited from an academic medical center and have pancreatic and breast cancers, compared with patients not receiving chemotherapy.

Risk for death was not significantly associated with chemotherapy use after adjustments were made for enrollment site and baseline performance status (adjusted hazard ratio, 0.85; 95% CI, 0.65 - 1.11) or when it was assessed within each ECOG stratum.

Chemotherapy use in patients with good (ECOG score = 1) baseline performance status was associated with a lower quality of life near death (OR, 0.35; 95% CI, 0.17-0.75; relative risk, 0.64; 95% CI, 0.46 - 0.88).

For patients with moderate (ECOG score = 2) and poor (ECOG score = 3) baseline performance status, the authors found that chemotherapy use did not improve the quality of their final weeks of life.

Better Discussions and More Data Needed

The editorialists note that this study raises some "fundamental questions," such as why chemotherapy did not affect survival. The chemotherapy itself was not defined, and targeted biologics, for example, were not specifically mentioned.

"At the same time, it is hard not to look at this study as the closest we are likely to come to obtaining proof of the real-world effectiveness of chemotherapy in patients at the end of life with cancer, as a placebo-controlled, double-blind, randomized trial seems unlikely," they write.

There are both physician and patient factors involved, they comment, adding that oncologists cannot precisely predict life expectancies. And even when prognosis is clearly communicated and the oncologist is honest about the limitations of treatment, many patients feel immense pressure to continue treatment. Some patients want systemic treatment until "the bitter end," they write.

"But chemotherapy should not be the automatic answer," Dr Blanke told Medscape Medical News. "It should be the exception and should only be given after a very frank, heart-to-heart discussion about the risks and probably minimal benefits."

"There are also patients who should not ethically be offered chemotherapy, regardless of how much they or their families want it," he added. "Usually an adequate discussion makes wanting chemotherapy less desirable, though not always."

The study authors emphasize that the lack of evidence showing a survival benefit should not be interpreted to mean that benefit does not exist. "Identifying better predictive biomarkers to select patients who are most likely to benefit from chemotherapy, especially in the palliative setting, is of paramount importance," they write.

Prospective studies of chemotherapy use in this population are also needed, the authors add, and should include repeated assessments of adverse effects of treatment, with quality of life and quality of life near death as the primary end points.

The study was supported in part by the grants from the National Institute of Mental Health, the National Cancer Institute, the National Institute of Minority Health and Health Disparities, Weill Cornell Medical College, and the Department of Veterans Affairs (Dr Garrido). Dr Prigerson reports no relevant financial relationships. Two of the coauthors report relationships with pharmaceutical companies: Dr LeBlanc has consulted for Helsinn Therapeutics, Epi-Q, and Boehringer Ingelheim, and Dr Neugut has consulted for Pfizer, Otsuka, United Biosource Corporation, and EHE Int. Dr Blanke and Dr Fromme have disclosed no relevant financial relationships.

JAMA Oncol. Published online July 23, 2015.

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