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Targeting Near the End of Life in Patients With Cancer
Vol. 45 No. 5 May 2013
Michael S. Putman, BA Pritzker School of Medicine The University of Chicago Chicago, Illinois, USA Farr A. Curlin, MD Department of Medicine and MacLean Center for Clinical Medical Ethics The University of Chicago Chicago, Illinois, USA http://dx.doi.org/10.1016/j.jpainsymman.2013.02.004
Reference 1. Dirksen KM, Hynds JA, Bhavsar AR, BrownSaltzman K. The existential question in palliative sedation: reply to Putman et al. J Pain Symptom Manage 2013;45:e1ee2.
Targeting Near the End of Life in Patients With Cancer To the Editor: We read with interest the recent study by Hui et al.1 regarding the use of targeted agents at the end of life in patients with cancer. We had earlier published a subset of our study in patients with lung cancer2 and, recently, the final report of a similar study in our patients with solid tumor malignancies.3 There are small inherent differences between the study by Hui et al.1 and ours such as the larger size of their study population and the obvious racial dissemblance as our study was conducted in an Asian context. In both studies, a significant proportion of patients received targeted therapy within one month of death, and more than 5% of all patients were receiving chemotherapy and/or targeted therapy within two weeks of dying. Hui et al.1 went on to profile that younger patients with hematological malignancies had a higher chance of being treated aggressively during their dying weeks. Perhaps it would be interesting to not only just show how many patients were receiving systemic treatment in their last one to three months but also to examine, among these patients, how many were initiated on a new line of treatment altogether, targeted or nontargeted. Although it may be difficult to prognosticate for a patient who has been receiving systemic treatment into the last three months of life and discontinue treatment, starting
Letters
e3
a new line of treatment within three months of death has a very different connotation and is likely to reflect more accurately the overaggressiveness of treatment of these patients. The use of targeted therapy in cancer on the whole has seen a meteoric rise in the past two decades, made possible by advances in molecular diagnostics. During this period, improvements in chemotherapeutic knowledge and the use of targeted agents to complement chemotherapy, or the use of targeted therapy as monotherapy, has contributed to improved survival in many tumor subtypes. However, most targeted therapies remain in the setting of palliation. Despite the purported benefit of being relatively more tumor selective, targeted therapy is not without its fair share of side effects and may impede on the quality of life of the patient in the terminal stage.4 Therefore, studies profiling the use of such agents at the end of life are becoming increasingly important. We concur that there is a need to develop guidelines for the establishment of the use of targeted therapy at the end of life and acknowledge the inherent difficulties given the dramatic responses that can be seen with some forms of targeted therapy, such as in lung cancer.5 It also is imperative to examine the impact of targeted agents in delaying pertinent end-of-life care or transition to a hospice. The decision of treatment at the end of life remains an intricate balance among the patient, the physician, and tumor factors. Although decedent studies remain a convenient and reliable method of profiling end-of-life care,6 we look forward to future prospective studies to document the impact that targeted agents may have for patients with advanced cancer. Thomas I Peng Soh, MD Alvin Seng Cheong Wong, MD Department of Hematology-Oncology National University Health System Singapore, Singapore http://dx.doi.org/10.1016/j.jpainsymman.2013.01.003
References 1. Hui D, Karuturi MS, Tanco KC, et al. Targeted agent use in cancer patients at the end of life. J Pain Symptom Manage 2013. [Epub ahead of print]. 2. Wong AS, Teo C, Lim SW, et al. Targeted therapy at the end of life for patients with lung cancer. J Palliat Med 2010;13:945e948.
e4
3. Soh TI, Yuen YC, Teo C, et al. Targeted therapy at the end of life in advanced cancer patients. J Palliat Med 2012;15:991e997. 4. Keefe DM, Bateman EH. Tumor control versus adverse events with targeted anticancer therapies. Nat Rev Clin Oncol 2011;9:98e109. 5. Langer CJ. The ‘‘Lazarus response’’ in treatmentna€ıve, poor performance status patients with nonsmall-cell lung cancer and epidermal growth factor receptor mutation. J Clin Oncol 2009;27:1350e1354. 6. Earle CC, Ayanian JZ. Looking back from death: the value of retrospective studies of end-of-life care. J Clin Oncol 2006;24:838e840.
Personalizing Treatment Decisions for Cancer Patients at the End of Life: Reply to Soh and Wong To the Editor: We would like to thank Soh and Wong for their insightful comments.1 They are correct in pointing out that initiation of a new systemic regimen in the last weeks of life is an indicator of aggressive end-of-life care. At the same time, we believe that the use of any chemotherapy in the last weeks of life, as documented in our present study and previous ones,2e4 is justified because this is the criterion adopted by the American Society of Clinical Oncology Quality Oncology Practice Initiative5 and the National Quality Forum.6 Patients with cancer on systemic therapy should be monitored regularly with a careful assessment before each treatment cycle (e.g., every three to four weeks). The decision to continue, hold, stop, or switch treatment is based on the risks (treatment toxicities),7 benefits (tumor response), and patient preference. Thus, administration of any systemic therapy, existing or new, when the disease clearly has progressed and/or the patient clearly has declined, calls into question its appropriateness. Given that clinicians often overestimate survival, we need to develop better prognostic and predictive factors to assist with treatment decision making at the end of life. Unfortunately, most oncology drug trials exclude patients with poor performance status and limited prognosis, making it difficult to accurately assess the utility of systemic therapy for patients with cancer at the end of life. Although the risks generally outweigh the
Letters
Vol. 45 No. 5 May 2013
benefits for these patients, treatment decisions are complicated by some notable exceptions. For instance, chemotherapy may be indicated for palliation in treatment-na€ıve patients with extensive stage small cell lung cancer even if they have a poor performance status.8 Similarly, targeted therapy may be considered in patients with metastatic non-small cell lung cancer with specific mutations even if they are bed bound.9 These patients are likely to derive a good clinical response, with significant improvement of their performance status, symptom burden, quality of life, and even quantity of life.10 There is currently a debate in the oncology community on whether erlotinib should be given indefinitely beyond disease progression because its discontinuation may result in rapid worsening of the disease.11 Prospective clinical trials and consensus guidelines on systemic therapy use at the end of life are urgently needed. In this era of personalized cancer care, we should not only target the tumor mutations but also tailor therapy to the patient’s prognosis, health status, and goals of care. David Hui, MD, MSc Eduardo Bruera, MD Department of Palliative Care and Rehabilitation Medicine M. D. Anderson Cancer Center Houston, Texas, USA http://dx.doi.org/10.1016/j.jpainsymman.2013.02.001
References 1. Soh TIP, Wong ASC. Targeting near the end of life in patients with cancer. J Pain Symptom Manage 2013;45:e3ee4. 2. Hui D, Elsayem A, Li Z, et al. Antineoplastic therapy use in patients with advanced cancer admitted to an acute palliative care unit at a comprehensive cancer center: a simultaneous care model. Cancer 2010;116:2036e2043. 3. Hui D, Karuturi MS, Tanco KC, et al. Targeted agent use in cancer patients at the end of life. J Pain Symptom Manage 2012. [Epub ahead of print]. 4. Hui D, Parsons H, Nguyen L, et al. Timing of palliative care referral and symptom burden in phase 1 cancer patients: a retrospective cohort study. Cancer 2010;116:4402e4409. 5. McNiff KK, Neuss MN, Jacobson JO, et al. Measuring supportive care in medical oncology practice: lessons learned from the quality oncology practice initiative. J Clin Oncol 2008;26:3832e3837.
Michael S. Putman, BA Pritzker School of Medicine The University of Chicago Chicago, Illinois, USA Farr A. Curlin, MD Department of Medicine and MacLean Center for Clinical Medical Ethics The University of Chicago Chicago, Illinois, USA http://dx.doi.org/10.1016/j.jpainsymman.2013.02.004
Reference 1. Dirksen KM, Hynds JA, Bhavsar AR, BrownSaltzman K. The existential question in palliative sedation: reply to Putman et al. J Pain Symptom Manage 2013;45:e1ee2.
Targeting Near the End of Life in Patients With Cancer To the Editor: We read with interest the recent study by Hui et al.1 regarding the use of targeted agents at the end of life in patients with cancer. We had earlier published a subset of our study in patients with lung cancer2 and, recently, the final report of a similar study in our patients with solid tumor malignancies.3 There are small inherent differences between the study by Hui et al.1 and ours such as the larger size of their study population and the obvious racial dissemblance as our study was conducted in an Asian context. In both studies, a significant proportion of patients received targeted therapy within one month of death, and more than 5% of all patients were receiving chemotherapy and/or targeted therapy within two weeks of dying. Hui et al.1 went on to profile that younger patients with hematological malignancies had a higher chance of being treated aggressively during their dying weeks. Perhaps it would be interesting to not only just show how many patients were receiving systemic treatment in their last one to three months but also to examine, among these patients, how many were initiated on a new line of treatment altogether, targeted or nontargeted. Although it may be difficult to prognosticate for a patient who has been receiving systemic treatment into the last three months of life and discontinue treatment, starting
Letters
e3
a new line of treatment within three months of death has a very different connotation and is likely to reflect more accurately the overaggressiveness of treatment of these patients. The use of targeted therapy in cancer on the whole has seen a meteoric rise in the past two decades, made possible by advances in molecular diagnostics. During this period, improvements in chemotherapeutic knowledge and the use of targeted agents to complement chemotherapy, or the use of targeted therapy as monotherapy, has contributed to improved survival in many tumor subtypes. However, most targeted therapies remain in the setting of palliation. Despite the purported benefit of being relatively more tumor selective, targeted therapy is not without its fair share of side effects and may impede on the quality of life of the patient in the terminal stage.4 Therefore, studies profiling the use of such agents at the end of life are becoming increasingly important. We concur that there is a need to develop guidelines for the establishment of the use of targeted therapy at the end of life and acknowledge the inherent difficulties given the dramatic responses that can be seen with some forms of targeted therapy, such as in lung cancer.5 It also is imperative to examine the impact of targeted agents in delaying pertinent end-of-life care or transition to a hospice. The decision of treatment at the end of life remains an intricate balance among the patient, the physician, and tumor factors. Although decedent studies remain a convenient and reliable method of profiling end-of-life care,6 we look forward to future prospective studies to document the impact that targeted agents may have for patients with advanced cancer. Thomas I Peng Soh, MD Alvin Seng Cheong Wong, MD Department of Hematology-Oncology National University Health System Singapore, Singapore http://dx.doi.org/10.1016/j.jpainsymman.2013.01.003
References 1. Hui D, Karuturi MS, Tanco KC, et al. Targeted agent use in cancer patients at the end of life. J Pain Symptom Manage 2013. [Epub ahead of print]. 2. Wong AS, Teo C, Lim SW, et al. Targeted therapy at the end of life for patients with lung cancer. J Palliat Med 2010;13:945e948.
e4
3. Soh TI, Yuen YC, Teo C, et al. Targeted therapy at the end of life in advanced cancer patients. J Palliat Med 2012;15:991e997. 4. Keefe DM, Bateman EH. Tumor control versus adverse events with targeted anticancer therapies. Nat Rev Clin Oncol 2011;9:98e109. 5. Langer CJ. The ‘‘Lazarus response’’ in treatmentna€ıve, poor performance status patients with nonsmall-cell lung cancer and epidermal growth factor receptor mutation. J Clin Oncol 2009;27:1350e1354. 6. Earle CC, Ayanian JZ. Looking back from death: the value of retrospective studies of end-of-life care. J Clin Oncol 2006;24:838e840.
Personalizing Treatment Decisions for Cancer Patients at the End of Life: Reply to Soh and Wong To the Editor: We would like to thank Soh and Wong for their insightful comments.1 They are correct in pointing out that initiation of a new systemic regimen in the last weeks of life is an indicator of aggressive end-of-life care. At the same time, we believe that the use of any chemotherapy in the last weeks of life, as documented in our present study and previous ones,2e4 is justified because this is the criterion adopted by the American Society of Clinical Oncology Quality Oncology Practice Initiative5 and the National Quality Forum.6 Patients with cancer on systemic therapy should be monitored regularly with a careful assessment before each treatment cycle (e.g., every three to four weeks). The decision to continue, hold, stop, or switch treatment is based on the risks (treatment toxicities),7 benefits (tumor response), and patient preference. Thus, administration of any systemic therapy, existing or new, when the disease clearly has progressed and/or the patient clearly has declined, calls into question its appropriateness. Given that clinicians often overestimate survival, we need to develop better prognostic and predictive factors to assist with treatment decision making at the end of life. Unfortunately, most oncology drug trials exclude patients with poor performance status and limited prognosis, making it difficult to accurately assess the utility of systemic therapy for patients with cancer at the end of life. Although the risks generally outweigh the
Letters
Vol. 45 No. 5 May 2013
benefits for these patients, treatment decisions are complicated by some notable exceptions. For instance, chemotherapy may be indicated for palliation in treatment-na€ıve patients with extensive stage small cell lung cancer even if they have a poor performance status.8 Similarly, targeted therapy may be considered in patients with metastatic non-small cell lung cancer with specific mutations even if they are bed bound.9 These patients are likely to derive a good clinical response, with significant improvement of their performance status, symptom burden, quality of life, and even quantity of life.10 There is currently a debate in the oncology community on whether erlotinib should be given indefinitely beyond disease progression because its discontinuation may result in rapid worsening of the disease.11 Prospective clinical trials and consensus guidelines on systemic therapy use at the end of life are urgently needed. In this era of personalized cancer care, we should not only target the tumor mutations but also tailor therapy to the patient’s prognosis, health status, and goals of care. David Hui, MD, MSc Eduardo Bruera, MD Department of Palliative Care and Rehabilitation Medicine M. D. Anderson Cancer Center Houston, Texas, USA http://dx.doi.org/10.1016/j.jpainsymman.2013.02.001
References 1. Soh TIP, Wong ASC. Targeting near the end of life in patients with cancer. J Pain Symptom Manage 2013;45:e3ee4. 2. Hui D, Elsayem A, Li Z, et al. Antineoplastic therapy use in patients with advanced cancer admitted to an acute palliative care unit at a comprehensive cancer center: a simultaneous care model. Cancer 2010;116:2036e2043. 3. Hui D, Karuturi MS, Tanco KC, et al. Targeted agent use in cancer patients at the end of life. J Pain Symptom Manage 2012. [Epub ahead of print]. 4. Hui D, Parsons H, Nguyen L, et al. Timing of palliative care referral and symptom burden in phase 1 cancer patients: a retrospective cohort study. Cancer 2010;116:4402e4409. 5. McNiff KK, Neuss MN, Jacobson JO, et al. Measuring supportive care in medical oncology practice: lessons learned from the quality oncology practice initiative. J Clin Oncol 2008;26:3832e3837.