Chemotherapy use and quality of life in cancer patients at the end of life: an integrative review

Best practices for management of advanced cancer are of global health concern, particularly in developing countries [1]. When curative strategies are exhausted, the focus of cancer care shifts to maintenance of quality of life (QOL) and extension of survival [2]. Studies indicate that – 20 to 50% of patients with advanced cancers receive chemotherapy (CT) towards end of life with the aims of extending survival and improving QOL [3‐5]. Such rigorous treatment strategies may contribute to death in non-preferred environments such as the intensive care unit (ICU), incurring additional costs for care that is often futile and that may also diminish QOL in the patients’ final days. Intensive medical management at end of life may also limit the opportunity for patients to receive hospice services, supportive care that focuses on enhancing comfort and promoting quality of life when facing death [6]. The purpose of the review was to examine the state of the science relative to the use of CT in patients with advanced cancers at the end of life, and to evaluate the impact of such treatments on patients QOL as they near death.

Chemotherapy generally refers to treatments aimed at stopping or eradicating the growth of cancer cells that are administered orally, intravenously, intrathecally, by injection, or subcutaneously depending on the type and stage of cancer being treated [7]. For patients with advanced cancers, many are now receiving oral antineoplastic agents [8]. Chemotherapies (CT) in general are associated with a host of side effects and symptoms that are specific to the type of agent and individualized patient characteristics. Numerous studies have identified the impact of CT on QOL, with some research suggesting that patients may experience improved QOL and length of survival when offered such treatments as a last alternative [9]. However, CT are also associated with increasing the cost of care at end of life due to the additional costs associated with need for pharmaceuticals, potential for blood products, laboratory and diagnostic testing, health professional support and unscheduled visits that result in hospitalization [10, 11].

Palliative care is aimed at providing comprehensive support and comfort via a multidisciplinary team approach to enhance QOL when cure is not an option [12]. Some research has shown that stoppage of intensive medical treatments and providing palliative care have improved both QOL and length of survival of advanced cancer patients [13]. Further, the incorporation of early specialized palliative care may reduce the risk of receiving CT during the final two weeks of life [14]. Many patients who have good performance status, however, receive palliative CT as they near end of life with the aim of increasing survival length and even to improve QOL [10].

According to the Health Service Research Committee of the American Society of Clinical Oncology (ASCO), CT can potentially improve QOL in late stages of life even if it doesn’t impact survival length [13]. Further, medical decision making relative to use of CT in patients nearing the end of life may be fostered by the development and availability of newer anticancer agents that have fewer side effects [15]. However, ASCO and the National Quality Forum have identified that other factors impact QOL at end of life (defined as final 30 days of life) and should be considered, such as unscheduled emergency room visits, the potential for lengthy hospitalizations, ICU admissions, and ICU deaths [16]. Recently, ASCO contended that stopping CT in cancer patients at the end of life is one of five factors which can improve the quality of patient care and reduce healthcare costs [16]. There remain limited studies that have systematically evaluated the effects of palliative CT on the QOL of cancer patients nearing end of life [4, 16, 17]. Some studies evaluate factors such as age, sex, type of cancer, and health care system characteristics while omitting information about perceived QOL [14]. Research findings suggest that culture may impact the utilization of aggressive treatment in patients with advanced cancer. For example, a study from Japan stated that only 3.7% of patients receive CT in their last 2 weeks of life [18]. In spite of increasing use of CT at end of life in recent years, the impact on patients' QOL remains equivocal. Therefore, the purpose of this review was to evaluate what is known about the use of CT and associated QOL in patients with advanced cancer approaching end of life.

Of the 13 studies, five studies were conducted in the United States (U.S.), six were from Europe, and one were from Australia and India respectively. Based on studies that reported this information, the sampling interval across the 13 studies were from 2002 to 2012 (Table 2).

Given progress in anti-cancer CT strategies for patients with advanced cancers, there is an increasing use of palliative CT at the end of life [15].

The purpose of this study was to evaluate relationships between use of palliative CT and QOL in patients with advanced cancer nearing end of life. Generally, the results of most of the selected studies indicated that palliative CT was associated with reduced QOL for patients. For example, such therapy was associated with increased necessity for cardiopulmonary resuscitation, mechanical ventilation, use of a feeding tube, and death in intensive care [3]. Further, such treatment was also associated with shortened survival and reduced quality of death [4].

Some patients with advanced cancer may prefer to receive aggressive treatment even if the therapies are associated with toxicities and side effects [30]. A study by Kao et al. found that patients who received palliative CT had shorter survival time and more frequent hospital admissions including unscheduled emergency department visits compared to those who did not receive CT at the end of life [26]. The goal of palliative CT is to maintain or improve QOL, improve length of survival and reduce symptoms in oncologic emergency conditions [1]. The usefulness of CT should always be considered by associated toxicities and side effects, given potential impact on QOL [1]. The presence of adverse effects from CT in cancer patients at the end of life was noted in the assessed studies [4, 9].

Early provision of palliative care with a multidisciplinary team has offered multiple benefits for patients with advanced cancer. For example, Temel and her colleagues compared two groups of patients who were newly diagnosed with metastatic cancer; one group that received palliative care with standard oncological care and the other group who received only standard oncology care. Findings demonstrated that the group that received integrated early palliative care had comparatively significant improvement in QOL, mood, and length of survival [12]. A complex issue is the use of palliative CT as a supportive strategy to improve length of survival, bolster QOL, assist with symptom management, and reduce disease progression given it may also result in more aggressive care at end of life [8]. Regimens and types of CT used in the palliative context vary. Further, it is often not clear that patients’ who receive these treatments have clearly addressed their end of life wishes and have advanced directives in place. Patients may die while receiving anti-cancer regimens because of death denial and/or communication barriers with their oncology team. For example, it may be more challenging to discuss stoppage of treatment as opposed to recommending further CT for patients who are nearing end of life [8] especially when patients are younger and have reasonable performance status. The mental health of patients at end of life and communication with their health providers may also impact the type of decisions patients will make in regards to sustaining treatment [31]. Without clear guidelines, the continued problems with medically futile treatments and untoward deaths in highly costly and non-preferred environments are likely to persist.

The review has limitations. These limitations include the possibility that articles that pertain to use of CT at end of life in patients with cancer were missed. For example, some studies may not include oral CT when evaluating use of CT at end of life [18]. Further, given the complex issues associated with patients who have advanced cancers, e.g., age, developmental stage, type of disease, comorbid conditions, etc., it can be challenging to determine best approaches to optimize individualized care at end of life. Cultural factors including the role of family caregivers may impact whether or not palliative CT is offered and utilized, and whether or not death occurs in a preferred environment. More research is needed that examines such issues across cultures, especially as more types of CT are made available to patients with advanced cancers. Research that includes diverse samples from global samples remains needed. Many of the current studies were conducted at major tertiary cancer centers so may not be reflective of practices in non-urban communities. Another limitation relates to the lag in sampling intervals among the published papers (2002–2012). Studies with more recent data collection could better reflect current practices.

The results of most selected studies show that palliative CT is associated with a decrease in QOL for patients. However, studies have been conducted primarily in European and American countries, and patients' cultural backgrounds may affect quality of life at the end of life. More research is needed in developing countries, including the Middle East and Asia.