Chemotherapy in end-of-life care
Authors: R. Heikkilä, S. Kaasa
Journal: Annals of Oncology (2017)

Evidence-based decisions regarding the optimal care for cancer patients near the end of life are challenging. A recent ASCO Expert Panel update recommended early referral to interdisciplinary palliative teams [1.Ferrell B.R. Temel J.S. Temin S. et al.Integration of palliative care into standard oncology care: American society of clinical oncology clinical practice guideline update.J Clin Oncol. 2017; 35: 96-112Crossref PubMed Scopus (1088) Google Scholar]. Early integration of palliative care may improve symptom control and quality of life. In one study where an improvement of survival was observed [2.Temel J.S. Greer J.A. Muzikansky A. et al.Early palliative care for patients with metastatic non-small-cell lung cancer.N Engl J Med. 2010; 363: 733-742Crossref PubMed Scopus (5031) Google Scholar] one may speculate if the survival benefit was caused by reduced survival in the control arm due to extensive use of chemotherapy during end of life care. Based on literature review, focus group interviews, and expert panel discussions, the intensity of anticancer treatment close to the end of life has been suggested as one of several factors influencing quality of life at this stage [3.Earle C.C. Park E.R. Lai B. et al.Identifying potential indicators of the quality of end-of-life cancer care from administrative data.J Clin Oncol. 2003; 21: 1133-1138Crossref PubMed Scopus (619) Google Scholar]. Among metastatic lung cancer patients, early palliative care has been found to half the odds of receiving intravenous chemotherapy within the last 60 days of life, while improving quality of life and maintaining the overall number of chemotherapy regimens [4.Greer J.A. Pirl W.F. Jackson V.A. et al.Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastatic non-small-cell lung cancer.J Clin Oncol. 2012; 30: 394-400Crossref PubMed Scopus (402) Google Scholar]. In a Swedish cohort study of patients with epithelial cancer, a co-variation between palliative chemotherapy during the last month of life and unfavorable outcome was found [5.Nappa U. Lindqvist O. Rasmussen B.H. Axelsson B. Palliative chemotherapy during the last month of life.Ann Oncol. 2011; 22: 2375-2380Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. In this issue ofAnnals of Oncology, a large retrospective French cohort study is presented, analyzing factors that influenced the use of chemotherapy at this stage of disease [6.Rochigneux P. Raoul J.L. Beaussant Y. et al.Use of chemotherapy near the end of life: what factors matter?.Ann Oncol. 2017; 28: 809-817Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar]. Using data from the French national hospital register, records from adult patients who died in these hospitals from solid metastatic tumors within a 4-year period (N = 297846) were retrieved. Patients with hematological malignancies and patients who had died from conditions other than cancer were excluded. In total, 39.1%, 19.5%, 11.3%, and 7% of the patients received chemotherapy during the last 3, 1 month, 2 weeks, and last week of life, respectively. As would be expected, older age and increased burden of chronic comorbidities were independently associated with lower rates of chemotherapy. More surprisingly, in multivariable analysis controlling for patient level confounding factors, major differences were found between institution categories. The probabilities of receiving chemotherapy outside clinical trials during the last month before death in comprehensive cancer centers and private for profit clinics were 43% and 40% higher, respectively, than in university hospitals. Additionally, treatment in centers with no palliative care unit increased the probability of receiving chemotherapy during the last month by 21%. At a population level, the optimal chemotherapy intensity during the last periods of life has not been established. At an individual level, the end of life period is hard to estimate. A retrospective analysis restricted to patients who died from their cancer is therefore not a perfect guide for prospective treatment decisions for individual patients. Patients may have solid tumors in which a therapy with relatively modest side-effects and high response rate and rapid response has been established. Even if the expected time of life without treatment of such a patient were less than 3 months, treatment might be appropriate. Yet, for the majority of patients, chemotherapy should not be given during the last month of life [4.Greer J.A. Pirl W.F. Jackson V.A. et al.Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastatic non-small-cell lung cancer.J Clin Oncol. 2012; 30: 394-400Crossref PubMed Scopus (402) Google Scholar,5.Nappa U. Lindqvist O. Rasmussen B.H. Axelsson B. Palliative chemotherapy during the last month of life.Ann Oncol. 2011; 22: 2375-2380Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. The observed trend of increased treatment intensity during the end of life period at a population level should therefore be reversed. We need better tools to estimate prognosis and to predict treatment response in patients near end of life to achieve this goal. Personalized treatment decisions remain the optimal standard, even during end of life. The concept of personalized cancer treatment is often used to describe targeted medical treatment directed towards the molecular tumor phenotype. We would emphasize that personalized treatment also means individual palliative considerations regarding the appropriate level of treatment intensity and institutional level of health care. From the French data presented here, this may be an issue even in highly specialized comprehensive cancer centers. Such an approach will regularly require communicative skills and time. Still, difficult discussions to prepare patients to accept lower treatment intensity should not be substituted by a new course of chemotherapy. In order to define the best standards for the optimal use of chemotherapy when patients are approaching death, we need more research on fundamental existential issues such as the value of prolonging life for weeks or a few months. These are difficult questions which should be debated in the public domain and not only within health care systems. With the limited validity of clinical classification systems to predict life expectancy close to death, studies are needed to address this sub-cohort of cancer patients to develop and better test classification systems. Such new classification systems then need to be implemented into clinical practice, for example within care pathways specifically designed for cancer patients during their last months of life. These pathways should describe the appropriate commitments of palliative care. They should also delineate how patient reported outcome measures (PROMS) may be completed by the patients and be actively used as part of the shared decision making between the patients, his/her family, and the healthcare providers. Structural and organizational improvements in order to integrate palliative care into "mainstream oncology" should also be considered. Early integration of specialized palliative care has been shown to improve patients' symptom burden, reduce anxiety and depression, improve family care, and contribute to less time spent in hospital [7.Jordhoy M.S. Fayers P. Saltnes T. et al.A palliative-care intervention and death at home: a cluster randomised trial.Lancet. 2000; 356: 888-893Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar, 8.Morita T. Miyashita M. Yamagishi A. et al.Effects of a programme of interventions on regional comprehensive palliative care for patients with cancer: a mixed-methods study.Lancet Oncol. 2013; 14: 638-646Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 9.Zimmermann C. Swami N. Krzyzanowska M. et al.Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial.Lancet. 2014; 383: 1721-1730Abstract Full Text Full Text PDF PubMed Scopus (1108) Google Scholar]. The competence of specialists in an organizational structure of early specialist palliative care should be discussed and clarified. We believe that the palliative care specialist working within oncology needs to be specialized both in oncology and palliative care. The reimbursement system needs to favor the integration of palliative care by economical incentives given to the hospitals. In our country, Norway, such an incentive has had major impact on the development of the specialist palliative care [10.Kaasa S. Jordhoy M.S. Haugen DF. Palliative care in Norway: a national public health model.J Pain Symptom Manage. 2007; 33: 599-604Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar]. None declared.