Withdrawal of anticancer therapy in advanced disease: a systematic literature review.

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Clarke, G 
Johnston, S 
Corrie, P 

BACKGROUND: Current guidelines set out when to start anticancer treatments, but not when to stop as the end of life approaches. Conventional cytotoxic agents are administered intravenously and have major life-threatening toxicities. Newer drugs include molecular targeted agents (MTAs), in particular, small molecule kinase-inhibitors (KIs), which are administered orally. These have fewer life-threatening toxicities, and are increasingly used to palliate advanced cancer, generally offering additional months of survival benefit. MTAs are substantially more expensive, between £2-8 K per month, and perceived as easier to start than stop. METHODS: A systematic review of decision-making concerning the withdrawal of anticancer drugs towards the end of life within clinical practice, with a particular focus on MTAs. Nine electronic databases searched. PRISMA guidelines followed. RESULTS: Forty-two studies included. How are decisions made? Decision-making was shared and ongoing, including stopping, starting and trying different treatments. Oncologists often experienced 'professional role dissonance' between their self-perception as 'treaters', and talking about end of life care. Why are decisions made? Clinical factors: disease progression, worsening functional status, treatment side-effects. Non-clinical factors: physicians' personal experience, values, emotions. Some patients continued treatment to maintain 'hope', often reflecting limited understanding of palliative goals. When are decisions made? Limited evidence reveals patients' decisions based upon quality of life benefits. Clinicians found timing withdrawal particularly challenging. Who makes the decisions? Decisions were based within physician-patient interaction. CONCLUSIONS: Oncologists report that decisions around stopping chemotherapy treatment are challenging, with limited evidence-based guidance outside of clinical trial protocols. The increasing availability of oral MTAs is transforming the management of incurable cancer; blurring boundaries between active treatment and palliative care. No studies specifically addressing decision-making around stopping MTAs in clinical practice were identified. There is a need to develop an evidence base to support physicians and patients with decision-making around the withdrawal of these high cost treatments.

Antineoplastic Agents, Clinical Decision-Making, Humans, Neoplasms, Terminal Care, Time Factors, Withholding Treatment
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BMC Cancer
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Springer Science and Business Media LLC
This independent research was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire and Peterborough at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We are grateful for the administrative support of Angela Harper. GC is the guarantor. Dr Gemma Clarke was funded by was funded by the University of Cambridge and the NIHR (National Institute of Heath Research) CLAHRC (Collaborations for Leadership in Applied Health Research and Care) East of England. Dr Simon Johnston was funded by the University of Cambridge and the Wellcome Trust. Dr Pippa Corrie was funded by the Cambridge University Hospitals NHS Foundation Trust. Ms. Isla Kuhn was funded by the University of Cambridge Library. Dr Stephen Barclay was funded by the University of Cambridge and the NIHR (National Institute of Heath Research) CLAHRC (Collaborations for Leadership in Applied Health Research and Care) East of England.