A review of systemic anticancer therapy in disease palliation

A review of systemic anticancer therapy in disease palliation Abstract Background Systemic anticancer therapy (SACT) is a collective term to describe the growing number of differing therapies used in malignancy to achieve palliation. Improving symptoms, quality of life (QOL) and where possible quantity of life are the goals of these treatments. Sources of data A comprehensive literature review was undertaken using Medline, Embase and the Cochrane database. Areas of agreement The use of palliative SACT can lead to increases in symptom control, QOL and survival. The breadth of treatable cancers has increased along with the number of therapeutic options. Areas of controversy The increasing use of SACT in the last weeks of life and the lack of consistency about the terms Supportive Care/Best Supportive Care in the trial setting. Growing points Integration between oncology and other palliative services leads to better outcomes. Areas timely for developing research Improved prognostication tools to elucidate which patients will benefit from SACT. chemotherapy, systemic anticancer therapy, palliation, supportive care Introduction The role of palliative chemotherapy in improving both quality and quantity of life in people diagnosed with an incurable malignancy is continuing to evolve. The advent of newer agents such as tyrosine kinase inhibitors, monoclonal antibodies and immunotherapies which along with palliative chemotherapy are collectively termed systemic anticancer therapy (SACT) has seen a surge in the number of patients treated. This article aims to review the role of SACT in disease palliation through review of published data and guidance. Methods A comprehensive literature search of all published reviews and studies between 2000 and 2017 using the terms ‘palliative’, ‘chemotherapy’, systemic anticancer therapy’, ‘supportive care’ and ‘Quality of life’ using Medline, Embase and Cochrane database was undertaken. Abstracts were reviewed by the two authors and full articles were identified and reviewed. Those whereby interventions included radiotherapy as a concurrent palliative option or those whereby they were testing tools to identify quality of life scales were excluded. Haematological systemic therapies and paediatric studies were also excluded. Where the impact of palliative chemotherapy on Quality of Life (QOL) was the aim of the study or review were included. Additionally a ‘snowball’ approach was undertaken whereby any reference not identified as part of the primary search but included in the reviewed article was obtained where deemed relevant and agreed by the authors. Results The goals of chemotherapy in disease palliation The goal of palliative chemotherapy is to assist patients in living both longer and better.1 Systemic anticancer therapies, such as palliative chemotherapy, may decrease disease burden through cancer cell kill thereby improving symptom control, changing the natural course of disease and in some situations prolong life. These gains are reliant on the chosen therapy achieving the required amount of cell kill to afford these benefits and are at the expense of a variety of potential toxicities and time invested in undertaking treatment. Because neither benefit nor toxicity is guaranteed there is clearly an element of uncertainty with SACT; the risk of having more side effects than symptom relief is real. Traditional intravenous chemotherapies can predictably cause patients to feel less well within the first two weeks of administration, before any advantage of treatment is seen. When the SACT is effective this can result in a brief decline in QOL due to toxic effects1; when the response is less than hoped it can decrease overall symptom control and shorten life.2 As of result of these uncertainties, there clearly needs to be careful consideration and communication between the patient and the oncologist regarding the risk/benefit ratio for that specific patient before embarking on SACT. The American Society of Clinical Oncology (ASCO) provide guidelines which describe a number of essential requirements to palliation in cancer.3 An emphasis on exploring patient’s understanding of illness, prognosis and clarification of treatment goals with the pursuit of assisted decision making in addition to addressing both the patient and carers symptom, psychological and care needs is fundamental to these guidelines and good shared decision making.3 Clinicians and patients perspectives on value Good quality shared decision making relies on an understanding of what is valued by a patient and their caregivers. This is individual, personal and not always predictable. People who have been diagnosed with a terminal illness may value small chances of benefit more highly than the staff who administer the treatment. A British study of attitudes to chemotherapy found that patients would accept a toxic treatment for a 1% chance of cure, 10% chance of symptom relief, or the chance to prolong life by only 12 months.4 Their physicians and nurses however would require a 50% chance of cure, 75% chance of symptom relief and 24–60 months added survival to want to proceed with chemotherapy.4 Their willingness to undergo aggressive treatment with major adverse effects for a small chance of benefit, when their physicians or nurses would not, is mirrored in studies outside the United Kingdom (UK).5–7 Whilst the study comparing views of healthcare professionals and patients is quite old, a more recent study looking at patient and physician preferences for chemotherapy similarly showed that patients were more likely to chose to have chemotherapy with only a modest survival benefits compared to doctors.8 Furthermore those patients prepared to undergo experimental therapies in the form of early phase clinical trials have reported that they would accept mortality rates of 10% alongside no degree of certainty of benefit.7 Evidence suggests patients’ value honesty in their decision-making process highly. In a study of 126 terminally ill pts, 98% said they wanted their oncologist to be realistic and truthful. Honest explanation of potential benefits and risks of palliative interventions clearly facilitates good decision making, however patients also desire honesty about prognosis and survival.9 That said there is evidence that, despite having been given a palliative diagnosis, patients can have unrealistic beliefs regarding the efficacy of treatment. The reasons for this can be multifactorial including doctors not wanting to remove hope, and patients not being able to understand or accept a terminal prognosis.10 In this context it is understandable how clinicians may feel pressured by patients and their families to prescribe SACT even when they believe that there may be little benefit. Whilst oncologists have been found to be fairly accurate in estimating whether a patient is likely to die within a 12 month period, their ability to make more detailed predictions on prognosis and survival is less accurate.11 The accuracy of prognostic estimation by oncologists is reported to be as low as 20–35%.2,12 A recent meta-analysis found that cancer physicians consistently over estimated prognosis by at least 30%.12 Current UK guidelines advise against SACT within 30 days of death, whilst American guidelines recommend avoidance within 2 weeks of death.13,14 There is evidence that those patients receiving treatment near the end of life are more frequently admitted to hospital, less likely to die at home and less likely to enter hospice care.2,15,16 Despite these recommendations reports suggest increasing numbers of patients receive ongoing administration of SACT near the end of life.16 American patients receiving chemotherapy within the last 2 weeks of life increased from 13.7% in 1993 to 18.5% by 199 6.17 Between 2000 and 2003 43% of lung cancer patients were given chemotherapy within the last month of life and 20% within the last 2 weeks of life.18 Furthermore, a 2007 retrospective Swedish study found 23% of patients received chemotherapy within the last month of life.2 One of the strongest indicators of a patient being close to their terminal phase is performance status (PS), a measure of functional capability.19 SACT is not usually recommended for those patients with poor PS.11,12 There are however occasions where both short predicted prognosis and poor performance status may not deter patient or cancer physician from SACT.20 The use of SACT may be acceptable in chemotherapy naïve patients with highly chemo-sensitive patients such as small cell lung cancer where response rates and symptom improvement rates are predictably up to 90% are an example of this.21 It is accepted practice to give this patient group SACT even when PS is poor and predicted prognosis may be very short. Whilst a very high chance of benefit may clearly tip the decision point in favour of intervention, it is not clear how low a chance of response is acceptable to proceed with SACT. ASCO consensus group were unable to decide on a minimal benefit for which chemotherapy was indicated, only that some benefit must be demonstrable and acknowledged that there are groups of patients for whom there is no evidence that chemotherapy is of any clinical benefit and that treating this patient group was ‘wasteful and unnecessary’.3 Quantifying the benefit of systemic anticancer therapy Traditionally SACT providing benefits in terms of improved survival and QOL has been limited to certain cancer groups. Data confirming benefit of traditional palliative chemotherapy in breast, colorectal, lung and pancreatic cancer have existed for many years.22–25 Other cancer groups, such as melanoma and renal cell carcinoma have traditionally been regarded as relatively chemo-resistant and treatment options have been limited. However the landscape of palliative therapies has changed dramatically over recent years with the arrival of what has been called ‘personalized medicine’. This term has been used to describe therapies that are directed to a specific cancer or genomic subgroup of cancer types, such as brca positive ovarian cancer (which is targeted by parp inhibitors such as olaparip) and include oral tyrosine kinase therapies, antibody therapies and immune check point inhibitors which have heralded a change in both the expected likelihood of benefit, and toxicity profiles. These therapeutic interventions, which are perhaps better described as tumour specific therapies rather than ‘personalized medicine’, along with palliative chemotherapy, are collectively termed SACT. These newer treatment options have differing toxicity profiles and expected responses compared to traditional palliative chemotherapy, but they still carrying significant risks of side effects. Renal cell carcinoma, a disease which does not respond to traditional chemotherapy can now be treated with oral targeted tyrosine kinase inhibitors and more recently with immune check point inhibitors. This has resulted in second and third line therapeutic options and predicted median survivals of around 28 months26 for patients who previously had little that could be realistically offered in terms of palliative options. Table 1 is a non-exhaustive representation of expected benefits from current first line SACT regimens for the four most common cancers presenting in the UK, these cancers account for 53% of cancer incidence.27 The QOL data includes health related questionnaires (HRQ) which assess quality of life through a range of measures including disease specific symptoms, for example breathless. Table 1 Expected benefits from first line SACT for breast, prostate, lung and colorectal cancer Disease type  Trial intervention  Efficacy  QOL data  Breast cancer  ER positive Breast cancer  Epirubicin vs fluorouracil, epirubicin and cyclophosphamide28  RR – 48% vs 55% OS – 16 vs 18 mo  QOL increased in epirubicin arm  HER 2 positive Breast Cancer  Trastuzumab and Docetaxel +/− Pertuzumab29  RR – 80% vs 69% PFS – 19 vs 12 mo OS – 56.5 vs 40.8 mo  Median time to deterioration in HRQOL (TOI-PFB) 18.4 vs 18.3 weeks = ns  Prostate cancer  Castrate Resistant  Enzalutamide vs placebo30  OS – 32.4 vs 30.2 mo RR – 59% vs 5%  Median time to QOL deterioration 11.3 vs 5.6 mo  Lung cancer  Adenocarcinoma – no actionable mutation  Cisplatin/Pemetrexed +/– maintenance pemetrexed31  OS – 13.9 vs 11.0 mo ORR – 28.2 vs 30.6%  Hospitalizations due to study drugs 8.4% vs 3.3% EQ-5D scores – no significantly different32  Adenocarcinoma – activating EGFR mutation  Erlotinib vs platinum based doublet33  PFS – 13.7 vs 4.6 mo OS – 22.8 vs 27.2 mo ORR – 83 vs 36%  Total FACT-L –OR 6.69 favouring Erlotinib TOI – OR 8.07 favouring Erlotinib LCS – OR -7.54 favouring Erlotinib  Adenocarcinoma – ALK rearrangement  Crizotinib vs Cisplatin or Carboplatin and Pemetrexed34  ORR – 74 vs 45% PFS – 10.9 vs 7 mo  QLQ-LC13, QLQ-C30 and EQ-5D all favour Crizotinib  NSCLC – High PD-L1 expression  Pembrolizumab vs platinum doublet35  PFS – 10.3 vs 6 mo ORR – 45% vs 28%  HRQOL improved in 40% pts having Pembrolizumab vs 26.5% for chemo36  Colorectal cancer  Mutated RAS colorectal cancer  5-Fluorouracil and Leucovorin +/− Oxaliplatin37  PFS – 9.0 vs 6.2 mo ORR – 50.7 vs 22.3% OS – 16.2 vs 14.7 mo  No significant difference in median survival Time to deterioration in Global Health Status longer with combination treatment  Wild type RAS colorectal cancer  Irinotecan, 5-fluorouracil and Leucovorin +/− Cetuximab20  PFS – 9.9 vs 8.7 ORR – 59.3% vs 43.2% OS – 24.9 vs 21.0 mo  Global Health Status/QOL no significant38  Key    mOS = median Overall Survival PFS = Progression Free Survival OR = Odds Ratio ER = Oestrogen Receptor  ORR = Overall Response Rate Mo = Months Ns = not significant QOL = Quality of Life (HRQOL, EQ-5D, FACT-L, TOI, LCS, QLQ-LC13, EQ-5D, HRQOL are all QOL scoring tools)  Disease type  Trial intervention  Efficacy  QOL data  Breast cancer  ER positive Breast cancer  Epirubicin vs fluorouracil, epirubicin and cyclophosphamide28  RR – 48% vs 55% OS – 16 vs 18 mo  QOL increased in epirubicin arm  HER 2 positive Breast Cancer  Trastuzumab and Docetaxel +/− Pertuzumab29  RR – 80% vs 69% PFS – 19 vs 12 mo OS – 56.5 vs 40.8 mo  Median time to deterioration in HRQOL (TOI-PFB) 18.4 vs 18.3 weeks = ns  Prostate cancer  Castrate Resistant  Enzalutamide vs placebo30  OS – 32.4 vs 30.2 mo RR – 59% vs 5%  Median time to QOL deterioration 11.3 vs 5.6 mo  Lung cancer  Adenocarcinoma – no actionable mutation  Cisplatin/Pemetrexed +/– maintenance pemetrexed31  OS – 13.9 vs 11.0 mo ORR – 28.2 vs 30.6%  Hospitalizations due to study drugs 8.4% vs 3.3% EQ-5D scores – no significantly different32  Adenocarcinoma – activating EGFR mutation  Erlotinib vs platinum based doublet33  PFS – 13.7 vs 4.6 mo OS – 22.8 vs 27.2 mo ORR – 83 vs 36%  Total FACT-L –OR 6.69 favouring Erlotinib TOI – OR 8.07 favouring Erlotinib LCS – OR -7.54 favouring Erlotinib  Adenocarcinoma – ALK rearrangement  Crizotinib vs Cisplatin or Carboplatin and Pemetrexed34  ORR – 74 vs 45% PFS – 10.9 vs 7 mo  QLQ-LC13, QLQ-C30 and EQ-5D all favour Crizotinib  NSCLC – High PD-L1 expression  Pembrolizumab vs platinum doublet35  PFS – 10.3 vs 6 mo ORR – 45% vs 28%  HRQOL improved in 40% pts having Pembrolizumab vs 26.5% for chemo36  Colorectal cancer  Mutated RAS colorectal cancer  5-Fluorouracil and Leucovorin +/− Oxaliplatin37  PFS – 9.0 vs 6.2 mo ORR – 50.7 vs 22.3% OS – 16.2 vs 14.7 mo  No significant difference in median survival Time to deterioration in Global Health Status longer with combination treatment  Wild type RAS colorectal cancer  Irinotecan, 5-fluorouracil and Leucovorin +/− Cetuximab20  PFS – 9.9 vs 8.7 ORR – 59.3% vs 43.2% OS – 24.9 vs 21.0 mo  Global Health Status/QOL no significant38  Key    mOS = median Overall Survival PFS = Progression Free Survival OR = Odds Ratio ER = Oestrogen Receptor  ORR = Overall Response Rate Mo = Months Ns = not significant QOL = Quality of Life (HRQOL, EQ-5D, FACT-L, TOI, LCS, QLQ-LC13, EQ-5D, HRQOL are all QOL scoring tools)  In addition to a changing landscape of systemic anticancer therapies, there have been real advances in supportive drugs available to reduce chemotherapy side effects. The arrival of 5-HT3 antagonists has transformed emetic experiences; the advent of granulocyte-colony stimulating factor has reduced the risk of febrile neutropenia and the modernization of chemotherapy support services such as dedicated triage lines and acute oncology services has improved the patient experience.39 However despite new regimens, supportive therapies and associated care delivery many of which have undoubtedly improved the patient outcomes, these schedules remain palliative, with fewer than 50% of newer drugs improving survival by more than 3 months.40 Aids to decision making Giving patients sufficient information to make an informed decision on which interventions will allow them the chance to maximize good palliation, taking into account their values requires shared decision making between oncologist, patient and carers. Research has shown that information sharing on the survival benefit of palliative chemotherapy is vague or non-existent in ~70% of oncology patient interactions and that prognosis is only discussed 39% of the time.41,42 However, it has also shown that patients want this information in order to participate fully in decision-making.22 Furthermore, patients that have a more accurate understanding of their cancer trajectory when discussing treatment goals are more likely to favour supportive therapies rather than aggressive ones.22 This suggests that more accurate estimations of survival may serve to avoid SACT in the last weeks of life. The European Association for Palliative Care have identified different factors that correlate with actual patient survival and include PS, signs or symptoms of cancer-anorexia-cachexia syndrome, delirium, dyspnoea and biological factors such as leucocytosis, lymphocytopenia and C-reactive protein.19 A number of palliative prognostic scoring systems have been produced to predict survival, the common features between these scores include PS, laboratory values and location of disease.43–51 In addition patient and care provider support tools to enhance communication within consultations can improve the quality of decisions made. These include tables of suggested prompts or questions to enhance decision making in the initial consultation between patient and cancer physician, and flow charts emphasising the balance between effective palliation and side effects may also assist ongoing effective decision making once SACT has been initiated.9,52 An integrated approach to palliative treatment The World Health Organization (WHO) defines palliative care as ‘as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual’.53 Whilst it may be clear from the point of diagnosis, or when relapse occurs, that treatment is palliative in nature, patient understanding of the treatment aims in this situation can be variable. One study looking at the expectations of the outcomes of treatment for women undergoing second or third line chemotherapy for ovarian cancer found that 42% believed that treatment would have a moderately high to high probability of curing their disease.54 The historical perception, particularly in trials where the gain for patients from chemotherapy was uncertain, has been a choice between SACT and supportive care (SC)/best supportive care (BSC). Although WHO has been clear that this should mean randomizing between SACT and palliative care the interpretation of SC/BSC in the trial setting has been variable, raising concerns about the validity of such comparisons. A systemic literature review between 1980 and 2012 demonstrated that there is significant variation in how SC/BSC are interpreted.55 This may potentially lead to patients not receiving some palliative interventions including routine holistic assessments, transfusions, radiotherapy and access to palliative care specialists. Access to these types of therapies should be regarded as a critical element of SC/BSC and in their absence may well have contributed to poorer QOL and survival outcomes in patients receiving SC/BSC as opposed to SACT. A randomized study comparing standard oncology care versus standard oncology care plus early palliative care intervention in patients with metastatic non-small cell lung cancer demonstrated improved mood, QOL scores and less aggressive end of life care for those patients randomized to the integrated oncology/palliative care arm. Furthermore, those randomized to the palliative care arm had a 2.7 month improvement in their overall survival. Precisely why this survival benefit was seen remains unclear but may reflect a combination of both improved symptom control and cessation of potentially harmful chemotherapy at a stage where the risk of harm has begun to outweigh the benefit.56 ASCO recommended that patients with advanced cancer should receive access to palliative care services at an early stage of the disease course, in addition to any active oncological treatment.57 However many providers in the USA will only fund this when it has been agreed that the patient is in the last 6 months of life. Referral to hospice and palliative care services may potentially limit subsequent access to some oncological and therapeutic interventions due to current palliative care funding provision by healthcare providers such as Medicare and Medicaid. In the UK there is a combination of both statutory and third sector providers delivering a range of palliative care services which are free at the point of contact. This means that access is potentially easier but there remains anxiety and confusion amongst both clinicians and patients about referring patients to palliative care and hospice services. In a survey of medical oncologists and midlevel providers at a cancer centre the term palliative care was found to be regarded as a barrier to referral, clinicians preferring the term ‘supportive care’ as they believed the term palliative care was more likely to cause distress and a reduction in hope for patients and their families.58 Confusion regarding the precise meaning of the terms ‘palliative care’ was also reported in a study by Hui et al. the resulting recommendation being for ‘palliative care’ and ‘hospice care’ to sit within a framework of Supportive Care.59 Historically therapeutic modalities used to treat this patient group, particularly as their cancer progresses, have been applied in a binary fashion, i.e. either ‘active treatment’ or ‘palliative care/BSC/SC’. This has been exacerbated by a lack of clarity from clinicians about what the latter three terms actually mean. There is increasing evidence that a more multidisciplinary team approach to the management of this patient population can result in an improved outcome clinically, and potentially at a reduced cost.60 There is an argument that we move away from regarding BSC as withdrawal of oncological interventions in the last months of life and move to an integrated multispecialty approach with input from specialist palliative care, primary care providers as well as social, psychological and spiritual service providers in addition to oncological treatment at all stages of the patients journey where indicated.13 In this way we move away from a binary treatment approach to a more holistic, patient focused approach more in keeping with the WHO definition of palliative care. Further emerging themes In addition to the increasing speed and variety of new therapies available for disease palliation, the rapidly changing environment both culturally and socially, affect changes that are difficult for clinicians, patients and carers to keep apace. As well as textbooks, word of mouth and the media increasingly patients and their families access the internet and social media for information.61 The plethora of information freely available via reputable third sector websites (cancer specific charities, forums and patient advisory groups) can support the patient and caregiver in their decision making, improve confidence in the advice they are given by healthcare professionals and offer support through a variety of mechanisms. Social media and non-specialist websites can potentially offer all of these advantages to service users, but carries with it risks of inaccuracies and frank misinformation which could conversely potentially adversely affect patients’ health as a consequence of patients altering medication regimes or failing to follow clinical advice based on information accessed.62 It can be difficult for non-specialists to separate, anecdote, opinion and fact and it can be equally challenging for clinical teams to support families in processing the information they receive. However despite these potential challenges patients and oncologists report that this ‘information seeking’ behaviour does not affect the patient–physician relationship.61 What does the future look like The aspirations of future palliative treatment of this patient group should have its foundations on effective communication centred on honesty about the likely prognosis, benefits and toxicities of any intervention and what the patient values the most in this context. This is reliant on adequate and accurate information being available to both patient and health professionals. Clinical research incorporating QOL measures is now already the norm, as shown in Table 1. However research incorporating QOL measures that include not only physical aspects of disease, but also psychological, social and sexual function remains uncommon. A study looking at QOL at the end of life by assessing caregiver’s ratings of patients’ physical and mental distress in the last week of life for those patients with a predicted survival of <6 months found those patients receiving chemotherapy did not have an improved survival, they also found no improvement in their quality of death (QOD).63 A randomized study of early palliative care involvement in a cancer centre versus usual care utilized a number of QOL measures. This study found improved QOL, improved QOD and improved patient satisfaction; despite this there was no improvement in spiritual wellbeing.64 An alternative route is to prospectively evaluate those QOL factors which are most important to the patients. A schedule for evaluation of individual QOL has been devised that evaluates what the patient feels dictates QOL. This involves the patient identifying their five most important QOL factors which are then measured prospectively within the clinical trial.65 It is also important that research data are aligned with real-life clinical practice. A process of continual validation of patient and clinical experience is vital to ensure the applicability of advice and information given to patients and their caregivers. Programmes of assessing and benchmarking patient experiences and outcomes through quality indicators which include response rates, survival, patient feedback, end of life experience and emotional wellbeing are increasingly being encouraged through international initiatives and adopted within cancer centres.14,66 In addition more accurate tools to support patient specific prognostication would support discussions regarding appropriateness of SACT. Delivering quality information, symptom control, goal and value led palliative interventions requires interdisciplinary team working. Early intervention with specialized palliative care teams improves the chances of this being successful. This can improve QOL, increase physical and mental wellbeing outcomes for caregivers, improves timely access to hospice care and in some studies has been suggested to improve survival.16,56,57 Whilst early intervention has been suggested to constitute palliative care interaction within 8 weeks of diagnosis of an incurable cancer ASCO do not specify timelines for this intervention but do recommend interdisciplinary palliative care management for all patients with advanced disease alongside standard oncology care.56 Conclusion The landscape of therapeutic options for cancer palliation has dramatically changed over recent years resulting in more treatment options, higher response rates, improvement in survival and changing toxicity profiles. However evidence also suggests that, despite guidelines to the contrary, increasing numibers of patients are receiving SACT in the last weeks of life. There appears to remain a disconnect between patient and doctor understanding and expectations of treatment outcomes. These factors make an emphasis on communication, honesty and frank discussion on benefits versus risks perhaps even more important than in the past. However, tools to support prognostication by clinicians is an area of significant importance for further research to aid decision making for clinicians, patients and their carers. There is also increasing evidence that a multidisciplinary approach to cancer palliation which includes palliative and hospice care from the start is of benefit however this remains aspirational in many parts of the world. Conflict of interest statement The authors have no potential conflicts of interest. Author Biography Dr C.M. Usborne MB ChB, FRCP, MRCGP, MSc, Dip Pal Care Ethics, is a consultant in palliative medicine, Clinical Lead for End of Life and Clinical Director for Cancer Services in North Wales. She has an interest in advance care planning. Dr A.P. Mullard MB BCH MRCP (Medical Oncology) UK, PGCert Cancer Studies, Dip Medical Education is a consultant medical oncologist; clinical lead for ESMO Designated Centre of Integrated Oncology and Palliative Care unit in the Alaw unit, leads palliative chemotherapy clinical trials and is regional lead for unknown primary. References 1 Blanke CD, Fromme EK. Chemotherapy near the end of life. First-and thirds and fourth (line) – do no harm. JAMA Oncol  2015; 1: 785– 6. Google Scholar CrossRef Search ADS PubMed  2 Nappa U, Lindquist O, Rasmussen BH, et al.  . Palliative chemotherapy during the last month of life. Ann Oncol  2011; 22: 2375– 80. Google Scholar CrossRef Search ADS PubMed  3 American Society of Clinical Oncology Outcomes Working Group. Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. J Clin Oncol  1996; 14: 671– 9. CrossRef Search ADS PubMed  4 Slevin ML, Stubbs L, Plant HJ, et al.  . Attitudes to chemotherapy; comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ  1990; 300: 1458– 60. Google Scholar CrossRef Search ADS PubMed  5 Matsuyama R, Reddy S, Smith T. Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol  2006; 24: 3490– 6. Google Scholar CrossRef Search ADS PubMed  6 Silvestri G, Pritchard R, Welch HG. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. Br J Med  1998; 317: 771– 5. Google Scholar CrossRef Search ADS   7 Agrawal M, Grady C, Fairclough D, et al.  . Patients’ decision-making process regarding participation in phase I oncology research. J Clin Oncol  2006; 24: 4479– 84. Google Scholar CrossRef Search ADS PubMed  8 Vaz-Luis I, O’Neill A, Sepucha K, et al.  . Survival benefit needed to undergo chemotherapy: patient and physician preferences. Cancer  2017; 123: 2821– 8. Google Scholar CrossRef Search ADS PubMed  9 Harrington SE, Smith TJ. The Role of chemotherapy at the end of life: ‘when is enough, enough?’. JAMA  2008; 299: 2667– 78. Google Scholar CrossRef Search ADS PubMed  10 Ghandourh WA. Palliative care in cancer: managing patients’ expectations. J Med Radiat Sci  2016; 63: 242– 57. Google Scholar CrossRef Search ADS PubMed  11 Moss AH, Lunney JR, Culp S, et al.  . Prognostic significance of the ‘surprise’ question in cancer patients. J Palliat Med  2010; 13: 837– 40. Google Scholar CrossRef Search ADS PubMed  12 Amano K, Maeda I, Shimoyama S, et al.  . The accuracy of physcicans’ clinical predictions of survival in patients with advanced cancer. J Pain Symptom Manag  2015; . Pii:S0885-3924 (15)00161-X. 13 NCAT. Chemotherapy Services in England: Ensuring quality and safety A report from the National Chemotherapy Advisory Group.2009. Accessed March 2017 on: http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_104501.pdf 14 QOPI. Accessed March 2017 on: http://www.instituteforquality.org/files/copy-qopi-measures-and-reporting-pathways-fall-16-public-websitexlsx 15 Chan W-L, Lam K-O, Siu W-K, et al.  . Chemotherapy at end-of-life: an integration of oncology and palliative team. Support Care Cancer  2016; 24: 1421– 7. Google Scholar CrossRef Search ADS PubMed  16 Greer JA, Pirl WF, Jackson VA, et al.  . Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastic non-small-cell lung cancer. J Clin Oncol  2012; 30: 394– 400. Google Scholar CrossRef Search ADS PubMed  17 Earle CC, Neville BA, Landrum MB, et al.  . Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol  2004; 22: 315– 21. Google Scholar CrossRef Search ADS PubMed  18 Murillo JR, Koeller J. Chemotherapy given near the end of life by community oncologists for advanced non-small cell lung cancer. Oncologist  2006; 11: 1095– 9. Google Scholar CrossRef Search ADS PubMed  19 Maltoni M, Caraceni A, Brunelli C, et al.  . Steering Committee of the European Association for Palliative Care. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations – a study by the Stering Committee of the European Association of Palliative Care. J Clin Oncol  2005; 23: 6240– 8. Google Scholar CrossRef Search ADS PubMed  20 Van Cutsem E, Köhne CH, Hitre E, et al.  . Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med  2009; 360: 1408– 17. Google Scholar CrossRef Search ADS PubMed  21 Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer  2000; 83: 8– 15. Google Scholar CrossRef Search ADS PubMed  22 Kadakia KC, Moynihan TJ, Smith TJ, et al.  . Palliative communications: addressing chemotherapy in patients with advanced cancer. Ann Oncol  2012; 23: ii29– 32. Google Scholar CrossRef Search ADS   23 Scheithauer W, Rosen H, Kornek GC, et al.  . Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. Br Med J  1993; 306: 752– 5. Google Scholar CrossRef Search ADS   24 Van Hoff DD, Goodwin AL, Garcia L, et al.  . Advances in the treatment of patiens with pancreatic cancer: improvement in symptoms and survival time. Br J Cancer  1998; 78: 9– 13. Google Scholar CrossRef Search ADS   25 Cullen MH, Billingham LJ, Woodroffe CM, et al.  . Mitomycin, ifosfamide and cisplatin in unresectable non-small cell lung cancer: effects on survival and quality of life. J Clin Oncol  1999; 17: 3188– 94. Google Scholar CrossRef Search ADS PubMed  26 Heng DY, Choueiri TK, Rini BI, et al.  . Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann Oncol  2014; 25: 149– 54. Google Scholar CrossRef Search ADS PubMed  27 Cancer Research UK. Accessed February 2017 at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared. 28 Joensuu H, Holli K, Heikkinen M, et al.  . Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial. J Clin Oncol  1998; 16: 3720– 30. Google Scholar CrossRef Search ADS PubMed  29 Swain SM, Baselga J, Kim SB, et al.  . CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med  2015; 372: 724– 34. Google Scholar CrossRef Search ADS PubMed  30 Beer TM, Armstrong AJ, Rathkopf DE, et al.  . for the PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med  2014; 371: 424– 33. Google Scholar CrossRef Search ADS PubMed  31 Paz-AresL G, de Marinis F, Dediu M, et al.  . PARAMOUNT: final overall survival results of the Phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non–small-cell lung cancer. J Clin Oncol  2013; 31: 2895– 2902. Google Scholar CrossRef Search ADS PubMed  32 Gridelli C, de Marinis F, Pujol JL, et al.  . Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexedversus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol  2012; 7: 1713– 21. Google Scholar CrossRef Search ADS PubMed  33 Chen G, Feng J, Zhou C, et al.  . Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol  2013; 24: 1615– 22. Google Scholar CrossRef Search ADS PubMed  34 Solomon BJ, Mok T, Kim DW, et al.  . PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med  2014; 371: 2167– 77. Google Scholar CrossRef Search ADS PubMed  35 Reck M, Rodríguez-Abreu D, Robinson AG, et al.  . KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med  2016; 375: 1823– 33. Google Scholar CrossRef Search ADS PubMed  36 Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al.  . Health-related quality of life for pembrolizumab vs chemotherapy in advanced NSCLC with PD-L1 TPS ≥50%: data from KEYNOTE-024. Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria. 37 De Gramont A, Figer A, Seymour M, et al.  . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol  2000; 18: 2938– 47. Google Scholar CrossRef Search ADS PubMed  38 Yamaguchi K, Ando M, Ooki A, et al.  . Quality of life analysis in patients with ras wild-type metastatic colorectal cancer treated with first-line cetuximab plus chemotherapy. Clin Colorectal Cancer  2016; ; pii: S1533-0028(16)30124-4. 39 Gregory ER, Ettinger DS. 5-HT3 receptor agonists for the prevention of chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs  1998; 55: 173– 89. Google Scholar CrossRef Search ADS PubMed  40 Sala-Vega S, Liopoulos O, Mossialos E. Assessment of overall survival, quality of life and safety benefits associated with new cancer medications. JAMA Oncol  2016; Doi:10.1001/jamaoncol.2016.4166.pmid/;28033447. 41 Audrey S, Abel J, Blazeby JM, et al.  . What oncologists tell patients about survival benefits of palliative chemotherapy and implications for informed consent: qualitative study. BMJ  2008; 337: a752. Google Scholar CrossRef Search ADS PubMed  42 Koedoot CG, Oort FL, de Haan RJ, et al.  . The content and amount of information given by medical oncologist when telling patients with advanced cancer what their treatment options are: palliative chemtoerhapy and watchful-waiting. Eur J Cancer  2004; 40: 225– 35. Google Scholar CrossRef Search ADS PubMed  43 Maltoni M, Nanni O, Pirovano M, et al.  . Successful validation of the palliative prognostic score in terminally ill cancer patietns. Italian multicentre study group on palliative care. J Pain Symptom Manag  1999; 17: 240– 7. Google Scholar CrossRef Search ADS   44 Morita T, Tsunoda J, Inoue S, et al.  . The palliative prognostic index: a scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer  1999; 7: 128– 33. Google Scholar CrossRef Search ADS PubMed  45 Scarpi E, Maltoni M, Miceli R, et al.  . Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium. Oncologist  2011; 16: 1793– 9. Google Scholar CrossRef Search ADS PubMed  46 Baba M, Maeda I, Morita T, et al.  . Independent validation of the modified prognosis palliative care study predictor models in three palliative care settings. J Pain Symptom Manage  2015; 49: 852– 60. Google Scholar CrossRef Search ADS   47 Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidermiol  1992; 45: 613– 9. Google Scholar CrossRef Search ADS   48 Downing M, Lau F, Lesperance M, et al.  . Meta-analysis of survivl prediction with palliative performance scale. J Palliat Care  2007; 23: 245– 52. Google Scholar PubMed  49 Douglas E, McMillan DC. Towards a simple objective framework for the investigation and treatment of cancer cachexia: the Glasgow Prognostic Score. Cancer Treat Rev  2014; 40: 685– 91. Google Scholar CrossRef Search ADS PubMed  50 Chuang RB, Hu WY, Chiu TY, et al.  . Prediction of survival in terminal patients in Taiwan: constructing a prognostic scale. J Pain SymptomManag  2004; 28: 115– 22. Google Scholar CrossRef Search ADS   51 Chen YT, Ho CT, Hsu HS, et al.  . Objective palliative score among patietns with advanced cancer. J Pain Symptom Manag  2015; 49: 690– 6. Google Scholar CrossRef Search ADS   52 Archer VR, Billingham LJ, Cullen MH. Palliative chemotherapy: no longer a contradiction in terms. Oncologist  1999; 4: 470– 7. Google Scholar PubMed  53 WHO. Accessed February 2017 at: - http://www.who.int/cancer/palliative/definition/en/ 54 Doyle C, Crump M, Pintilie M, et al.  . Does palliative chemotherapy palliate? Evaluation of expectations, outcomes and costs in women recieving chemotherapy for advanced ovarian cancer. J Clin Oncol  2001; 19: 1266– 74. Google Scholar CrossRef Search ADS PubMed  55 Lee RT, Ramchandran K, Sanft T, et al.  . Implementation of supportive care and best supportive care interventions in clinical trials enrolling patients with cancer. Ann Oncol  2015; 26: 1838– 45. Google Scholar CrossRef Search ADS PubMed  56 Temel JS, Greer JA, Muzikansky A, et al.  . Early palliative care for patients with metastatic non-small-cell lung cancer. N Eng J Med  2010; 363: 733– 42. Google Scholar CrossRef Search ADS   57 Ferrell BR, Temel JS, Temin S, et al.  . Integration of palliative care in to standard oncology care: Americal Society of clinical oncology clinical practice guideline update. J Clin Oncol  2017; 35: 96– 112. Google Scholar CrossRef Search ADS PubMed  58 Fadul N, Elsayem A, Palmer JL, et al.  . Supportive versus palliative care: what’s in a name? Cancer  2009; 115: 2013– 21. Google Scholar CrossRef Search ADS PubMed  59 Hui D, De La Cruz M, Mori M, et al.  . Concepts and definitions for ‘supportive care,’ ‘best supportive care,’ ‘palliative care,’ and ‘hospice care’ in the published literature, dictionaries, and textbooks. Support Care Cancer  2013; 21: 659– 85. Google Scholar CrossRef Search ADS PubMed  60 Gade G, Venohr I, Conner D, et al.  . Impact of an Inpatient Palliative Care Team: a randomized controlled trial. J Pall Med  2008; 11: 180– 90. Google Scholar CrossRef Search ADS   61 Eysenbach G, Powell J, Kuss O, et al.  . Emperical studies assessing the quality of health information for consumers on the World Wide Web. JAMA  2002; 287: 2691– 2700. Google Scholar CrossRef Search ADS PubMed  62 Chen X, Sui LL. Impact of the media and the Internet on Oncology: Survey of Cancer Patients and Oncologists in Canada. J Clin Oncol  2001; 19( 23): 4291– 4297. Google Scholar CrossRef Search ADS PubMed  63 Prigerson HG, Bao Y, Shah MA, et al.  . Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol  2015; 1: 778– 84. Google Scholar CrossRef Search ADS PubMed  64 Zimmerman C, SSwami N, Kryzanowska M, et al.  . Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet  2014; 383: 1721– 30. Google Scholar CrossRef Search ADS PubMed  65 O’Boyle CA, McGee H, Hickey A, et al.  . Individual quality of life in patients undergoing hip replacement. Lancet  1992; 339: 1088– 91. Google Scholar CrossRef Search ADS PubMed  66 McNiff K. The quality oncology practice initiative. J Oncol Pract  2006; 2: 26– 30. Google Scholar PubMed  © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Medical Bulletin Oxford University Press

A review of systemic anticancer therapy in disease palliation

Loading next page...
 
/lp/ou_press/a-review-of-systemic-anticancer-therapy-in-disease-palliation-BxbiaqYcb7
Publisher
Oxford University Press
Copyright
© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
ISSN
0007-1420
eISSN
1471-8391
D.O.I.
10.1093/bmb/ldx045
Publisher site
See Article on Publisher Site

Abstract

Abstract Background Systemic anticancer therapy (SACT) is a collective term to describe the growing number of differing therapies used in malignancy to achieve palliation. Improving symptoms, quality of life (QOL) and where possible quantity of life are the goals of these treatments. Sources of data A comprehensive literature review was undertaken using Medline, Embase and the Cochrane database. Areas of agreement The use of palliative SACT can lead to increases in symptom control, QOL and survival. The breadth of treatable cancers has increased along with the number of therapeutic options. Areas of controversy The increasing use of SACT in the last weeks of life and the lack of consistency about the terms Supportive Care/Best Supportive Care in the trial setting. Growing points Integration between oncology and other palliative services leads to better outcomes. Areas timely for developing research Improved prognostication tools to elucidate which patients will benefit from SACT. chemotherapy, systemic anticancer therapy, palliation, supportive care Introduction The role of palliative chemotherapy in improving both quality and quantity of life in people diagnosed with an incurable malignancy is continuing to evolve. The advent of newer agents such as tyrosine kinase inhibitors, monoclonal antibodies and immunotherapies which along with palliative chemotherapy are collectively termed systemic anticancer therapy (SACT) has seen a surge in the number of patients treated. This article aims to review the role of SACT in disease palliation through review of published data and guidance. Methods A comprehensive literature search of all published reviews and studies between 2000 and 2017 using the terms ‘palliative’, ‘chemotherapy’, systemic anticancer therapy’, ‘supportive care’ and ‘Quality of life’ using Medline, Embase and Cochrane database was undertaken. Abstracts were reviewed by the two authors and full articles were identified and reviewed. Those whereby interventions included radiotherapy as a concurrent palliative option or those whereby they were testing tools to identify quality of life scales were excluded. Haematological systemic therapies and paediatric studies were also excluded. Where the impact of palliative chemotherapy on Quality of Life (QOL) was the aim of the study or review were included. Additionally a ‘snowball’ approach was undertaken whereby any reference not identified as part of the primary search but included in the reviewed article was obtained where deemed relevant and agreed by the authors. Results The goals of chemotherapy in disease palliation The goal of palliative chemotherapy is to assist patients in living both longer and better.1 Systemic anticancer therapies, such as palliative chemotherapy, may decrease disease burden through cancer cell kill thereby improving symptom control, changing the natural course of disease and in some situations prolong life. These gains are reliant on the chosen therapy achieving the required amount of cell kill to afford these benefits and are at the expense of a variety of potential toxicities and time invested in undertaking treatment. Because neither benefit nor toxicity is guaranteed there is clearly an element of uncertainty with SACT; the risk of having more side effects than symptom relief is real. Traditional intravenous chemotherapies can predictably cause patients to feel less well within the first two weeks of administration, before any advantage of treatment is seen. When the SACT is effective this can result in a brief decline in QOL due to toxic effects1; when the response is less than hoped it can decrease overall symptom control and shorten life.2 As of result of these uncertainties, there clearly needs to be careful consideration and communication between the patient and the oncologist regarding the risk/benefit ratio for that specific patient before embarking on SACT. The American Society of Clinical Oncology (ASCO) provide guidelines which describe a number of essential requirements to palliation in cancer.3 An emphasis on exploring patient’s understanding of illness, prognosis and clarification of treatment goals with the pursuit of assisted decision making in addition to addressing both the patient and carers symptom, psychological and care needs is fundamental to these guidelines and good shared decision making.3 Clinicians and patients perspectives on value Good quality shared decision making relies on an understanding of what is valued by a patient and their caregivers. This is individual, personal and not always predictable. People who have been diagnosed with a terminal illness may value small chances of benefit more highly than the staff who administer the treatment. A British study of attitudes to chemotherapy found that patients would accept a toxic treatment for a 1% chance of cure, 10% chance of symptom relief, or the chance to prolong life by only 12 months.4 Their physicians and nurses however would require a 50% chance of cure, 75% chance of symptom relief and 24–60 months added survival to want to proceed with chemotherapy.4 Their willingness to undergo aggressive treatment with major adverse effects for a small chance of benefit, when their physicians or nurses would not, is mirrored in studies outside the United Kingdom (UK).5–7 Whilst the study comparing views of healthcare professionals and patients is quite old, a more recent study looking at patient and physician preferences for chemotherapy similarly showed that patients were more likely to chose to have chemotherapy with only a modest survival benefits compared to doctors.8 Furthermore those patients prepared to undergo experimental therapies in the form of early phase clinical trials have reported that they would accept mortality rates of 10% alongside no degree of certainty of benefit.7 Evidence suggests patients’ value honesty in their decision-making process highly. In a study of 126 terminally ill pts, 98% said they wanted their oncologist to be realistic and truthful. Honest explanation of potential benefits and risks of palliative interventions clearly facilitates good decision making, however patients also desire honesty about prognosis and survival.9 That said there is evidence that, despite having been given a palliative diagnosis, patients can have unrealistic beliefs regarding the efficacy of treatment. The reasons for this can be multifactorial including doctors not wanting to remove hope, and patients not being able to understand or accept a terminal prognosis.10 In this context it is understandable how clinicians may feel pressured by patients and their families to prescribe SACT even when they believe that there may be little benefit. Whilst oncologists have been found to be fairly accurate in estimating whether a patient is likely to die within a 12 month period, their ability to make more detailed predictions on prognosis and survival is less accurate.11 The accuracy of prognostic estimation by oncologists is reported to be as low as 20–35%.2,12 A recent meta-analysis found that cancer physicians consistently over estimated prognosis by at least 30%.12 Current UK guidelines advise against SACT within 30 days of death, whilst American guidelines recommend avoidance within 2 weeks of death.13,14 There is evidence that those patients receiving treatment near the end of life are more frequently admitted to hospital, less likely to die at home and less likely to enter hospice care.2,15,16 Despite these recommendations reports suggest increasing numbers of patients receive ongoing administration of SACT near the end of life.16 American patients receiving chemotherapy within the last 2 weeks of life increased from 13.7% in 1993 to 18.5% by 199 6.17 Between 2000 and 2003 43% of lung cancer patients were given chemotherapy within the last month of life and 20% within the last 2 weeks of life.18 Furthermore, a 2007 retrospective Swedish study found 23% of patients received chemotherapy within the last month of life.2 One of the strongest indicators of a patient being close to their terminal phase is performance status (PS), a measure of functional capability.19 SACT is not usually recommended for those patients with poor PS.11,12 There are however occasions where both short predicted prognosis and poor performance status may not deter patient or cancer physician from SACT.20 The use of SACT may be acceptable in chemotherapy naïve patients with highly chemo-sensitive patients such as small cell lung cancer where response rates and symptom improvement rates are predictably up to 90% are an example of this.21 It is accepted practice to give this patient group SACT even when PS is poor and predicted prognosis may be very short. Whilst a very high chance of benefit may clearly tip the decision point in favour of intervention, it is not clear how low a chance of response is acceptable to proceed with SACT. ASCO consensus group were unable to decide on a minimal benefit for which chemotherapy was indicated, only that some benefit must be demonstrable and acknowledged that there are groups of patients for whom there is no evidence that chemotherapy is of any clinical benefit and that treating this patient group was ‘wasteful and unnecessary’.3 Quantifying the benefit of systemic anticancer therapy Traditionally SACT providing benefits in terms of improved survival and QOL has been limited to certain cancer groups. Data confirming benefit of traditional palliative chemotherapy in breast, colorectal, lung and pancreatic cancer have existed for many years.22–25 Other cancer groups, such as melanoma and renal cell carcinoma have traditionally been regarded as relatively chemo-resistant and treatment options have been limited. However the landscape of palliative therapies has changed dramatically over recent years with the arrival of what has been called ‘personalized medicine’. This term has been used to describe therapies that are directed to a specific cancer or genomic subgroup of cancer types, such as brca positive ovarian cancer (which is targeted by parp inhibitors such as olaparip) and include oral tyrosine kinase therapies, antibody therapies and immune check point inhibitors which have heralded a change in both the expected likelihood of benefit, and toxicity profiles. These therapeutic interventions, which are perhaps better described as tumour specific therapies rather than ‘personalized medicine’, along with palliative chemotherapy, are collectively termed SACT. These newer treatment options have differing toxicity profiles and expected responses compared to traditional palliative chemotherapy, but they still carrying significant risks of side effects. Renal cell carcinoma, a disease which does not respond to traditional chemotherapy can now be treated with oral targeted tyrosine kinase inhibitors and more recently with immune check point inhibitors. This has resulted in second and third line therapeutic options and predicted median survivals of around 28 months26 for patients who previously had little that could be realistically offered in terms of palliative options. Table 1 is a non-exhaustive representation of expected benefits from current first line SACT regimens for the four most common cancers presenting in the UK, these cancers account for 53% of cancer incidence.27 The QOL data includes health related questionnaires (HRQ) which assess quality of life through a range of measures including disease specific symptoms, for example breathless. Table 1 Expected benefits from first line SACT for breast, prostate, lung and colorectal cancer Disease type  Trial intervention  Efficacy  QOL data  Breast cancer  ER positive Breast cancer  Epirubicin vs fluorouracil, epirubicin and cyclophosphamide28  RR – 48% vs 55% OS – 16 vs 18 mo  QOL increased in epirubicin arm  HER 2 positive Breast Cancer  Trastuzumab and Docetaxel +/− Pertuzumab29  RR – 80% vs 69% PFS – 19 vs 12 mo OS – 56.5 vs 40.8 mo  Median time to deterioration in HRQOL (TOI-PFB) 18.4 vs 18.3 weeks = ns  Prostate cancer  Castrate Resistant  Enzalutamide vs placebo30  OS – 32.4 vs 30.2 mo RR – 59% vs 5%  Median time to QOL deterioration 11.3 vs 5.6 mo  Lung cancer  Adenocarcinoma – no actionable mutation  Cisplatin/Pemetrexed +/– maintenance pemetrexed31  OS – 13.9 vs 11.0 mo ORR – 28.2 vs 30.6%  Hospitalizations due to study drugs 8.4% vs 3.3% EQ-5D scores – no significantly different32  Adenocarcinoma – activating EGFR mutation  Erlotinib vs platinum based doublet33  PFS – 13.7 vs 4.6 mo OS – 22.8 vs 27.2 mo ORR – 83 vs 36%  Total FACT-L –OR 6.69 favouring Erlotinib TOI – OR 8.07 favouring Erlotinib LCS – OR -7.54 favouring Erlotinib  Adenocarcinoma – ALK rearrangement  Crizotinib vs Cisplatin or Carboplatin and Pemetrexed34  ORR – 74 vs 45% PFS – 10.9 vs 7 mo  QLQ-LC13, QLQ-C30 and EQ-5D all favour Crizotinib  NSCLC – High PD-L1 expression  Pembrolizumab vs platinum doublet35  PFS – 10.3 vs 6 mo ORR – 45% vs 28%  HRQOL improved in 40% pts having Pembrolizumab vs 26.5% for chemo36  Colorectal cancer  Mutated RAS colorectal cancer  5-Fluorouracil and Leucovorin +/− Oxaliplatin37  PFS – 9.0 vs 6.2 mo ORR – 50.7 vs 22.3% OS – 16.2 vs 14.7 mo  No significant difference in median survival Time to deterioration in Global Health Status longer with combination treatment  Wild type RAS colorectal cancer  Irinotecan, 5-fluorouracil and Leucovorin +/− Cetuximab20  PFS – 9.9 vs 8.7 ORR – 59.3% vs 43.2% OS – 24.9 vs 21.0 mo  Global Health Status/QOL no significant38  Key    mOS = median Overall Survival PFS = Progression Free Survival OR = Odds Ratio ER = Oestrogen Receptor  ORR = Overall Response Rate Mo = Months Ns = not significant QOL = Quality of Life (HRQOL, EQ-5D, FACT-L, TOI, LCS, QLQ-LC13, EQ-5D, HRQOL are all QOL scoring tools)  Disease type  Trial intervention  Efficacy  QOL data  Breast cancer  ER positive Breast cancer  Epirubicin vs fluorouracil, epirubicin and cyclophosphamide28  RR – 48% vs 55% OS – 16 vs 18 mo  QOL increased in epirubicin arm  HER 2 positive Breast Cancer  Trastuzumab and Docetaxel +/− Pertuzumab29  RR – 80% vs 69% PFS – 19 vs 12 mo OS – 56.5 vs 40.8 mo  Median time to deterioration in HRQOL (TOI-PFB) 18.4 vs 18.3 weeks = ns  Prostate cancer  Castrate Resistant  Enzalutamide vs placebo30  OS – 32.4 vs 30.2 mo RR – 59% vs 5%  Median time to QOL deterioration 11.3 vs 5.6 mo  Lung cancer  Adenocarcinoma – no actionable mutation  Cisplatin/Pemetrexed +/– maintenance pemetrexed31  OS – 13.9 vs 11.0 mo ORR – 28.2 vs 30.6%  Hospitalizations due to study drugs 8.4% vs 3.3% EQ-5D scores – no significantly different32  Adenocarcinoma – activating EGFR mutation  Erlotinib vs platinum based doublet33  PFS – 13.7 vs 4.6 mo OS – 22.8 vs 27.2 mo ORR – 83 vs 36%  Total FACT-L –OR 6.69 favouring Erlotinib TOI – OR 8.07 favouring Erlotinib LCS – OR -7.54 favouring Erlotinib  Adenocarcinoma – ALK rearrangement  Crizotinib vs Cisplatin or Carboplatin and Pemetrexed34  ORR – 74 vs 45% PFS – 10.9 vs 7 mo  QLQ-LC13, QLQ-C30 and EQ-5D all favour Crizotinib  NSCLC – High PD-L1 expression  Pembrolizumab vs platinum doublet35  PFS – 10.3 vs 6 mo ORR – 45% vs 28%  HRQOL improved in 40% pts having Pembrolizumab vs 26.5% for chemo36  Colorectal cancer  Mutated RAS colorectal cancer  5-Fluorouracil and Leucovorin +/− Oxaliplatin37  PFS – 9.0 vs 6.2 mo ORR – 50.7 vs 22.3% OS – 16.2 vs 14.7 mo  No significant difference in median survival Time to deterioration in Global Health Status longer with combination treatment  Wild type RAS colorectal cancer  Irinotecan, 5-fluorouracil and Leucovorin +/− Cetuximab20  PFS – 9.9 vs 8.7 ORR – 59.3% vs 43.2% OS – 24.9 vs 21.0 mo  Global Health Status/QOL no significant38  Key    mOS = median Overall Survival PFS = Progression Free Survival OR = Odds Ratio ER = Oestrogen Receptor  ORR = Overall Response Rate Mo = Months Ns = not significant QOL = Quality of Life (HRQOL, EQ-5D, FACT-L, TOI, LCS, QLQ-LC13, EQ-5D, HRQOL are all QOL scoring tools)  In addition to a changing landscape of systemic anticancer therapies, there have been real advances in supportive drugs available to reduce chemotherapy side effects. The arrival of 5-HT3 antagonists has transformed emetic experiences; the advent of granulocyte-colony stimulating factor has reduced the risk of febrile neutropenia and the modernization of chemotherapy support services such as dedicated triage lines and acute oncology services has improved the patient experience.39 However despite new regimens, supportive therapies and associated care delivery many of which have undoubtedly improved the patient outcomes, these schedules remain palliative, with fewer than 50% of newer drugs improving survival by more than 3 months.40 Aids to decision making Giving patients sufficient information to make an informed decision on which interventions will allow them the chance to maximize good palliation, taking into account their values requires shared decision making between oncologist, patient and carers. Research has shown that information sharing on the survival benefit of palliative chemotherapy is vague or non-existent in ~70% of oncology patient interactions and that prognosis is only discussed 39% of the time.41,42 However, it has also shown that patients want this information in order to participate fully in decision-making.22 Furthermore, patients that have a more accurate understanding of their cancer trajectory when discussing treatment goals are more likely to favour supportive therapies rather than aggressive ones.22 This suggests that more accurate estimations of survival may serve to avoid SACT in the last weeks of life. The European Association for Palliative Care have identified different factors that correlate with actual patient survival and include PS, signs or symptoms of cancer-anorexia-cachexia syndrome, delirium, dyspnoea and biological factors such as leucocytosis, lymphocytopenia and C-reactive protein.19 A number of palliative prognostic scoring systems have been produced to predict survival, the common features between these scores include PS, laboratory values and location of disease.43–51 In addition patient and care provider support tools to enhance communication within consultations can improve the quality of decisions made. These include tables of suggested prompts or questions to enhance decision making in the initial consultation between patient and cancer physician, and flow charts emphasising the balance between effective palliation and side effects may also assist ongoing effective decision making once SACT has been initiated.9,52 An integrated approach to palliative treatment The World Health Organization (WHO) defines palliative care as ‘as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual’.53 Whilst it may be clear from the point of diagnosis, or when relapse occurs, that treatment is palliative in nature, patient understanding of the treatment aims in this situation can be variable. One study looking at the expectations of the outcomes of treatment for women undergoing second or third line chemotherapy for ovarian cancer found that 42% believed that treatment would have a moderately high to high probability of curing their disease.54 The historical perception, particularly in trials where the gain for patients from chemotherapy was uncertain, has been a choice between SACT and supportive care (SC)/best supportive care (BSC). Although WHO has been clear that this should mean randomizing between SACT and palliative care the interpretation of SC/BSC in the trial setting has been variable, raising concerns about the validity of such comparisons. A systemic literature review between 1980 and 2012 demonstrated that there is significant variation in how SC/BSC are interpreted.55 This may potentially lead to patients not receiving some palliative interventions including routine holistic assessments, transfusions, radiotherapy and access to palliative care specialists. Access to these types of therapies should be regarded as a critical element of SC/BSC and in their absence may well have contributed to poorer QOL and survival outcomes in patients receiving SC/BSC as opposed to SACT. A randomized study comparing standard oncology care versus standard oncology care plus early palliative care intervention in patients with metastatic non-small cell lung cancer demonstrated improved mood, QOL scores and less aggressive end of life care for those patients randomized to the integrated oncology/palliative care arm. Furthermore, those randomized to the palliative care arm had a 2.7 month improvement in their overall survival. Precisely why this survival benefit was seen remains unclear but may reflect a combination of both improved symptom control and cessation of potentially harmful chemotherapy at a stage where the risk of harm has begun to outweigh the benefit.56 ASCO recommended that patients with advanced cancer should receive access to palliative care services at an early stage of the disease course, in addition to any active oncological treatment.57 However many providers in the USA will only fund this when it has been agreed that the patient is in the last 6 months of life. Referral to hospice and palliative care services may potentially limit subsequent access to some oncological and therapeutic interventions due to current palliative care funding provision by healthcare providers such as Medicare and Medicaid. In the UK there is a combination of both statutory and third sector providers delivering a range of palliative care services which are free at the point of contact. This means that access is potentially easier but there remains anxiety and confusion amongst both clinicians and patients about referring patients to palliative care and hospice services. In a survey of medical oncologists and midlevel providers at a cancer centre the term palliative care was found to be regarded as a barrier to referral, clinicians preferring the term ‘supportive care’ as they believed the term palliative care was more likely to cause distress and a reduction in hope for patients and their families.58 Confusion regarding the precise meaning of the terms ‘palliative care’ was also reported in a study by Hui et al. the resulting recommendation being for ‘palliative care’ and ‘hospice care’ to sit within a framework of Supportive Care.59 Historically therapeutic modalities used to treat this patient group, particularly as their cancer progresses, have been applied in a binary fashion, i.e. either ‘active treatment’ or ‘palliative care/BSC/SC’. This has been exacerbated by a lack of clarity from clinicians about what the latter three terms actually mean. There is increasing evidence that a more multidisciplinary team approach to the management of this patient population can result in an improved outcome clinically, and potentially at a reduced cost.60 There is an argument that we move away from regarding BSC as withdrawal of oncological interventions in the last months of life and move to an integrated multispecialty approach with input from specialist palliative care, primary care providers as well as social, psychological and spiritual service providers in addition to oncological treatment at all stages of the patients journey where indicated.13 In this way we move away from a binary treatment approach to a more holistic, patient focused approach more in keeping with the WHO definition of palliative care. Further emerging themes In addition to the increasing speed and variety of new therapies available for disease palliation, the rapidly changing environment both culturally and socially, affect changes that are difficult for clinicians, patients and carers to keep apace. As well as textbooks, word of mouth and the media increasingly patients and their families access the internet and social media for information.61 The plethora of information freely available via reputable third sector websites (cancer specific charities, forums and patient advisory groups) can support the patient and caregiver in their decision making, improve confidence in the advice they are given by healthcare professionals and offer support through a variety of mechanisms. Social media and non-specialist websites can potentially offer all of these advantages to service users, but carries with it risks of inaccuracies and frank misinformation which could conversely potentially adversely affect patients’ health as a consequence of patients altering medication regimes or failing to follow clinical advice based on information accessed.62 It can be difficult for non-specialists to separate, anecdote, opinion and fact and it can be equally challenging for clinical teams to support families in processing the information they receive. However despite these potential challenges patients and oncologists report that this ‘information seeking’ behaviour does not affect the patient–physician relationship.61 What does the future look like The aspirations of future palliative treatment of this patient group should have its foundations on effective communication centred on honesty about the likely prognosis, benefits and toxicities of any intervention and what the patient values the most in this context. This is reliant on adequate and accurate information being available to both patient and health professionals. Clinical research incorporating QOL measures is now already the norm, as shown in Table 1. However research incorporating QOL measures that include not only physical aspects of disease, but also psychological, social and sexual function remains uncommon. A study looking at QOL at the end of life by assessing caregiver’s ratings of patients’ physical and mental distress in the last week of life for those patients with a predicted survival of <6 months found those patients receiving chemotherapy did not have an improved survival, they also found no improvement in their quality of death (QOD).63 A randomized study of early palliative care involvement in a cancer centre versus usual care utilized a number of QOL measures. This study found improved QOL, improved QOD and improved patient satisfaction; despite this there was no improvement in spiritual wellbeing.64 An alternative route is to prospectively evaluate those QOL factors which are most important to the patients. A schedule for evaluation of individual QOL has been devised that evaluates what the patient feels dictates QOL. This involves the patient identifying their five most important QOL factors which are then measured prospectively within the clinical trial.65 It is also important that research data are aligned with real-life clinical practice. A process of continual validation of patient and clinical experience is vital to ensure the applicability of advice and information given to patients and their caregivers. Programmes of assessing and benchmarking patient experiences and outcomes through quality indicators which include response rates, survival, patient feedback, end of life experience and emotional wellbeing are increasingly being encouraged through international initiatives and adopted within cancer centres.14,66 In addition more accurate tools to support patient specific prognostication would support discussions regarding appropriateness of SACT. Delivering quality information, symptom control, goal and value led palliative interventions requires interdisciplinary team working. Early intervention with specialized palliative care teams improves the chances of this being successful. This can improve QOL, increase physical and mental wellbeing outcomes for caregivers, improves timely access to hospice care and in some studies has been suggested to improve survival.16,56,57 Whilst early intervention has been suggested to constitute palliative care interaction within 8 weeks of diagnosis of an incurable cancer ASCO do not specify timelines for this intervention but do recommend interdisciplinary palliative care management for all patients with advanced disease alongside standard oncology care.56 Conclusion The landscape of therapeutic options for cancer palliation has dramatically changed over recent years resulting in more treatment options, higher response rates, improvement in survival and changing toxicity profiles. However evidence also suggests that, despite guidelines to the contrary, increasing numibers of patients are receiving SACT in the last weeks of life. There appears to remain a disconnect between patient and doctor understanding and expectations of treatment outcomes. These factors make an emphasis on communication, honesty and frank discussion on benefits versus risks perhaps even more important than in the past. However, tools to support prognostication by clinicians is an area of significant importance for further research to aid decision making for clinicians, patients and their carers. There is also increasing evidence that a multidisciplinary approach to cancer palliation which includes palliative and hospice care from the start is of benefit however this remains aspirational in many parts of the world. Conflict of interest statement The authors have no potential conflicts of interest. Author Biography Dr C.M. Usborne MB ChB, FRCP, MRCGP, MSc, Dip Pal Care Ethics, is a consultant in palliative medicine, Clinical Lead for End of Life and Clinical Director for Cancer Services in North Wales. She has an interest in advance care planning. Dr A.P. Mullard MB BCH MRCP (Medical Oncology) UK, PGCert Cancer Studies, Dip Medical Education is a consultant medical oncologist; clinical lead for ESMO Designated Centre of Integrated Oncology and Palliative Care unit in the Alaw unit, leads palliative chemotherapy clinical trials and is regional lead for unknown primary. References 1 Blanke CD, Fromme EK. Chemotherapy near the end of life. First-and thirds and fourth (line) – do no harm. JAMA Oncol  2015; 1: 785– 6. Google Scholar CrossRef Search ADS PubMed  2 Nappa U, Lindquist O, Rasmussen BH, et al.  . Palliative chemotherapy during the last month of life. Ann Oncol  2011; 22: 2375– 80. Google Scholar CrossRef Search ADS PubMed  3 American Society of Clinical Oncology Outcomes Working Group. Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. J Clin Oncol  1996; 14: 671– 9. CrossRef Search ADS PubMed  4 Slevin ML, Stubbs L, Plant HJ, et al.  . Attitudes to chemotherapy; comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ  1990; 300: 1458– 60. Google Scholar CrossRef Search ADS PubMed  5 Matsuyama R, Reddy S, Smith T. Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol  2006; 24: 3490– 6. Google Scholar CrossRef Search ADS PubMed  6 Silvestri G, Pritchard R, Welch HG. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. Br J Med  1998; 317: 771– 5. Google Scholar CrossRef Search ADS   7 Agrawal M, Grady C, Fairclough D, et al.  . Patients’ decision-making process regarding participation in phase I oncology research. J Clin Oncol  2006; 24: 4479– 84. Google Scholar CrossRef Search ADS PubMed  8 Vaz-Luis I, O’Neill A, Sepucha K, et al.  . Survival benefit needed to undergo chemotherapy: patient and physician preferences. Cancer  2017; 123: 2821– 8. Google Scholar CrossRef Search ADS PubMed  9 Harrington SE, Smith TJ. The Role of chemotherapy at the end of life: ‘when is enough, enough?’. JAMA  2008; 299: 2667– 78. Google Scholar CrossRef Search ADS PubMed  10 Ghandourh WA. Palliative care in cancer: managing patients’ expectations. J Med Radiat Sci  2016; 63: 242– 57. Google Scholar CrossRef Search ADS PubMed  11 Moss AH, Lunney JR, Culp S, et al.  . Prognostic significance of the ‘surprise’ question in cancer patients. J Palliat Med  2010; 13: 837– 40. Google Scholar CrossRef Search ADS PubMed  12 Amano K, Maeda I, Shimoyama S, et al.  . The accuracy of physcicans’ clinical predictions of survival in patients with advanced cancer. J Pain Symptom Manag  2015; . Pii:S0885-3924 (15)00161-X. 13 NCAT. Chemotherapy Services in England: Ensuring quality and safety A report from the National Chemotherapy Advisory Group.2009. Accessed March 2017 on: http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_104501.pdf 14 QOPI. Accessed March 2017 on: http://www.instituteforquality.org/files/copy-qopi-measures-and-reporting-pathways-fall-16-public-websitexlsx 15 Chan W-L, Lam K-O, Siu W-K, et al.  . Chemotherapy at end-of-life: an integration of oncology and palliative team. Support Care Cancer  2016; 24: 1421– 7. Google Scholar CrossRef Search ADS PubMed  16 Greer JA, Pirl WF, Jackson VA, et al.  . Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastic non-small-cell lung cancer. J Clin Oncol  2012; 30: 394– 400. Google Scholar CrossRef Search ADS PubMed  17 Earle CC, Neville BA, Landrum MB, et al.  . Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol  2004; 22: 315– 21. Google Scholar CrossRef Search ADS PubMed  18 Murillo JR, Koeller J. Chemotherapy given near the end of life by community oncologists for advanced non-small cell lung cancer. Oncologist  2006; 11: 1095– 9. Google Scholar CrossRef Search ADS PubMed  19 Maltoni M, Caraceni A, Brunelli C, et al.  . Steering Committee of the European Association for Palliative Care. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations – a study by the Stering Committee of the European Association of Palliative Care. J Clin Oncol  2005; 23: 6240– 8. Google Scholar CrossRef Search ADS PubMed  20 Van Cutsem E, Köhne CH, Hitre E, et al.  . Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med  2009; 360: 1408– 17. Google Scholar CrossRef Search ADS PubMed  21 Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer  2000; 83: 8– 15. Google Scholar CrossRef Search ADS PubMed  22 Kadakia KC, Moynihan TJ, Smith TJ, et al.  . Palliative communications: addressing chemotherapy in patients with advanced cancer. Ann Oncol  2012; 23: ii29– 32. Google Scholar CrossRef Search ADS   23 Scheithauer W, Rosen H, Kornek GC, et al.  . Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. Br Med J  1993; 306: 752– 5. Google Scholar CrossRef Search ADS   24 Van Hoff DD, Goodwin AL, Garcia L, et al.  . Advances in the treatment of patiens with pancreatic cancer: improvement in symptoms and survival time. Br J Cancer  1998; 78: 9– 13. Google Scholar CrossRef Search ADS   25 Cullen MH, Billingham LJ, Woodroffe CM, et al.  . Mitomycin, ifosfamide and cisplatin in unresectable non-small cell lung cancer: effects on survival and quality of life. J Clin Oncol  1999; 17: 3188– 94. Google Scholar CrossRef Search ADS PubMed  26 Heng DY, Choueiri TK, Rini BI, et al.  . Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann Oncol  2014; 25: 149– 54. Google Scholar CrossRef Search ADS PubMed  27 Cancer Research UK. Accessed February 2017 at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared. 28 Joensuu H, Holli K, Heikkinen M, et al.  . Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial. J Clin Oncol  1998; 16: 3720– 30. Google Scholar CrossRef Search ADS PubMed  29 Swain SM, Baselga J, Kim SB, et al.  . CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med  2015; 372: 724– 34. Google Scholar CrossRef Search ADS PubMed  30 Beer TM, Armstrong AJ, Rathkopf DE, et al.  . for the PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med  2014; 371: 424– 33. Google Scholar CrossRef Search ADS PubMed  31 Paz-AresL G, de Marinis F, Dediu M, et al.  . PARAMOUNT: final overall survival results of the Phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non–small-cell lung cancer. J Clin Oncol  2013; 31: 2895– 2902. Google Scholar CrossRef Search ADS PubMed  32 Gridelli C, de Marinis F, Pujol JL, et al.  . Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexedversus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol  2012; 7: 1713– 21. Google Scholar CrossRef Search ADS PubMed  33 Chen G, Feng J, Zhou C, et al.  . Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol  2013; 24: 1615– 22. Google Scholar CrossRef Search ADS PubMed  34 Solomon BJ, Mok T, Kim DW, et al.  . PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med  2014; 371: 2167– 77. Google Scholar CrossRef Search ADS PubMed  35 Reck M, Rodríguez-Abreu D, Robinson AG, et al.  . KEYNOTE-024 investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med  2016; 375: 1823– 33. Google Scholar CrossRef Search ADS PubMed  36 Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al.  . Health-related quality of life for pembrolizumab vs chemotherapy in advanced NSCLC with PD-L1 TPS ≥50%: data from KEYNOTE-024. Paper presented at: International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria. 37 De Gramont A, Figer A, Seymour M, et al.  . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol  2000; 18: 2938– 47. Google Scholar CrossRef Search ADS PubMed  38 Yamaguchi K, Ando M, Ooki A, et al.  . Quality of life analysis in patients with ras wild-type metastatic colorectal cancer treated with first-line cetuximab plus chemotherapy. Clin Colorectal Cancer  2016; ; pii: S1533-0028(16)30124-4. 39 Gregory ER, Ettinger DS. 5-HT3 receptor agonists for the prevention of chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs  1998; 55: 173– 89. Google Scholar CrossRef Search ADS PubMed  40 Sala-Vega S, Liopoulos O, Mossialos E. Assessment of overall survival, quality of life and safety benefits associated with new cancer medications. JAMA Oncol  2016; Doi:10.1001/jamaoncol.2016.4166.pmid/;28033447. 41 Audrey S, Abel J, Blazeby JM, et al.  . What oncologists tell patients about survival benefits of palliative chemotherapy and implications for informed consent: qualitative study. BMJ  2008; 337: a752. Google Scholar CrossRef Search ADS PubMed  42 Koedoot CG, Oort FL, de Haan RJ, et al.  . The content and amount of information given by medical oncologist when telling patients with advanced cancer what their treatment options are: palliative chemtoerhapy and watchful-waiting. Eur J Cancer  2004; 40: 225– 35. Google Scholar CrossRef Search ADS PubMed  43 Maltoni M, Nanni O, Pirovano M, et al.  . Successful validation of the palliative prognostic score in terminally ill cancer patietns. Italian multicentre study group on palliative care. J Pain Symptom Manag  1999; 17: 240– 7. Google Scholar CrossRef Search ADS   44 Morita T, Tsunoda J, Inoue S, et al.  . The palliative prognostic index: a scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer  1999; 7: 128– 33. Google Scholar CrossRef Search ADS PubMed  45 Scarpi E, Maltoni M, Miceli R, et al.  . Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium. Oncologist  2011; 16: 1793– 9. Google Scholar CrossRef Search ADS PubMed  46 Baba M, Maeda I, Morita T, et al.  . Independent validation of the modified prognosis palliative care study predictor models in three palliative care settings. J Pain Symptom Manage  2015; 49: 852– 60. Google Scholar CrossRef Search ADS   47 Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidermiol  1992; 45: 613– 9. Google Scholar CrossRef Search ADS   48 Downing M, Lau F, Lesperance M, et al.  . Meta-analysis of survivl prediction with palliative performance scale. J Palliat Care  2007; 23: 245– 52. Google Scholar PubMed  49 Douglas E, McMillan DC. Towards a simple objective framework for the investigation and treatment of cancer cachexia: the Glasgow Prognostic Score. Cancer Treat Rev  2014; 40: 685– 91. Google Scholar CrossRef Search ADS PubMed  50 Chuang RB, Hu WY, Chiu TY, et al.  . Prediction of survival in terminal patients in Taiwan: constructing a prognostic scale. J Pain SymptomManag  2004; 28: 115– 22. Google Scholar CrossRef Search ADS   51 Chen YT, Ho CT, Hsu HS, et al.  . Objective palliative score among patietns with advanced cancer. J Pain Symptom Manag  2015; 49: 690– 6. Google Scholar CrossRef Search ADS   52 Archer VR, Billingham LJ, Cullen MH. Palliative chemotherapy: no longer a contradiction in terms. Oncologist  1999; 4: 470– 7. Google Scholar PubMed  53 WHO. Accessed February 2017 at: - http://www.who.int/cancer/palliative/definition/en/ 54 Doyle C, Crump M, Pintilie M, et al.  . Does palliative chemotherapy palliate? Evaluation of expectations, outcomes and costs in women recieving chemotherapy for advanced ovarian cancer. J Clin Oncol  2001; 19: 1266– 74. Google Scholar CrossRef Search ADS PubMed  55 Lee RT, Ramchandran K, Sanft T, et al.  . Implementation of supportive care and best supportive care interventions in clinical trials enrolling patients with cancer. Ann Oncol  2015; 26: 1838– 45. Google Scholar CrossRef Search ADS PubMed  56 Temel JS, Greer JA, Muzikansky A, et al.  . Early palliative care for patients with metastatic non-small-cell lung cancer. N Eng J Med  2010; 363: 733– 42. Google Scholar CrossRef Search ADS   57 Ferrell BR, Temel JS, Temin S, et al.  . Integration of palliative care in to standard oncology care: Americal Society of clinical oncology clinical practice guideline update. J Clin Oncol  2017; 35: 96– 112. Google Scholar CrossRef Search ADS PubMed  58 Fadul N, Elsayem A, Palmer JL, et al.  . Supportive versus palliative care: what’s in a name? Cancer  2009; 115: 2013– 21. Google Scholar CrossRef Search ADS PubMed  59 Hui D, De La Cruz M, Mori M, et al.  . Concepts and definitions for ‘supportive care,’ ‘best supportive care,’ ‘palliative care,’ and ‘hospice care’ in the published literature, dictionaries, and textbooks. Support Care Cancer  2013; 21: 659– 85. Google Scholar CrossRef Search ADS PubMed  60 Gade G, Venohr I, Conner D, et al.  . Impact of an Inpatient Palliative Care Team: a randomized controlled trial. J Pall Med  2008; 11: 180– 90. Google Scholar CrossRef Search ADS   61 Eysenbach G, Powell J, Kuss O, et al.  . Emperical studies assessing the quality of health information for consumers on the World Wide Web. JAMA  2002; 287: 2691– 2700. Google Scholar CrossRef Search ADS PubMed  62 Chen X, Sui LL. Impact of the media and the Internet on Oncology: Survey of Cancer Patients and Oncologists in Canada. J Clin Oncol  2001; 19( 23): 4291– 4297. Google Scholar CrossRef Search ADS PubMed  63 Prigerson HG, Bao Y, Shah MA, et al.  . Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol  2015; 1: 778– 84. Google Scholar CrossRef Search ADS PubMed  64 Zimmerman C, SSwami N, Kryzanowska M, et al.  . Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet  2014; 383: 1721– 30. Google Scholar CrossRef Search ADS PubMed  65 O’Boyle CA, McGee H, Hickey A, et al.  . Individual quality of life in patients undergoing hip replacement. Lancet  1992; 339: 1088– 91. Google Scholar CrossRef Search ADS PubMed  66 McNiff K. The quality oncology practice initiative. J Oncol Pract  2006; 2: 26– 30. Google Scholar PubMed  © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

British Medical BulletinOxford University Press

Published: Mar 1, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off