- Email: [email protected]
Personalizing Treatment Decisions for Cancer Patients at the End of Life: Reply to Soh and Wong
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.
Vol. 45 No. 5 May 2013
6. National Quality Forum. A national framework and preferred practices for palliative and hospice care quality. 2006. Available from http://www.qualityfo rum.org/Publications/2006/12/A_National_Frame work_and_Preferred_Practices_for_Palliative_and_ Hospice_Care_Quality.aspx. Accessed January 29, 2013. 7. Niraula S, Seruga B, Ocana A, et al. The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol 2012;30:3012e3019. 8. Rehman S, Baka S, Lau S, et al. A review of the treatment strategies for small cell lung carcinoma patients with a poor performance status. Curr Respir Med Rev 2006;2:59e66. 9. Ahn HK, Jeon K, Yoo H, et al. Successful treatment with crizotinib in mechanically ventilated patients with ALK positive non-small-cell lung cancer. J Thorac Oncol 2013;8:250e253. 10. Lee SM, Khan I, Upadhyay S, et al. First-line erlotinib in patients with advanced non-smallcell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2012;13:1161e1170. 11. Park K, Tsai CM, Ahn MJ, et al. ASPIRATION: phase II study of continued erlotinib beyond RECIST progression in Asian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). [Abstract]. J Clin Oncol 2012;30(Suppl; abstr TPS7614). Available from http://www.asco.org/ASCOv2/Meetings/ Abstracts?&vmview¼abst_detail_view&confID¼114& abstractID¼98869. Accessed January 26, 2013.
Locked-In Syndrome as a Result of Cyclizine Administration To the Editor: Movement disorders, including akathisia, dystonia, and tardive dyskinesia, resulting from the use of antiemetic medications are not uncommon side effects in the palliative care setting. There have been a number of case reports of severe acute dystonic reactions after single doses of cyclizine1e4 and of transient paralysis also after single doses of cyclizine.5,6 Previously, the author has personally recognized only one movement disorder case after administration of cyclizine, a 78-year-old man with metastatic non-small cell lung cancer who developed tardive dyskinesia after taking oral cyclizine 25 mg three times a day for one week. The following case describes the
Letters
e5
development of locked-in syndrome one month after starting cyclizine.
Case A 24-year-old woman was diagnosed with bilateral serous papillary adenocarcinoma Stage IIIc in 2008. She underwent bilateral salpingooophorectomy, debulking, and omentectomy followed by multiple lines of chemotherapy. Her progress was complicated by recurrent small bowel obstructions, and her care was transferred to the palliative care team for supportive care in November 2012. She was admitted to the palliative care ward in early December 2012 with a malignant bowel obstruction characterized by feculent vomiting, absolute constipation, abdominal pain, and nausea. This settled with conservative management, and she was discharged home on a subcutaneous infusion of fentanyl 600 mcg and octreotide 300 mcg over 24 hours, subcutaneous cyclizine 25 mg twice a day, and intermittent subcutaneous fluids as requested by the patient and family, approximately 500 mL daily. The patient was managed at home by her family with support from the community palliative care team. Over the course of the following 30 days, she had intermittent vomiting episodes and pain. Fentanyl was titrated up to 900 mcg over 24 hours, octreotide to 600 mcg, and cyclizine to 25 mg three times a day. In early January 2013, she had another episode of feculent vomiting and then became unresponsive. The patient had expressed the wish to be admitted to the palliative care unit for her end-of-life care and her family arranged admission. She received intravenous fluids to see if rehydration would improve her condition, and fentanyl, octreotide, and cyclizine were continued at the same doses. She had no further vomiting and remained unresponsive, with her family and the staff expecting that she would soon die. After 72 hours of admission, it was noted by the medical staff that the patient’s eyes were open and she was following. She was unable to speak, move, or blink spontaneously or on command. The nursing staff reported that they were unable to administer mouth care because she was ‘‘biting down.’’ On questioning, her family reported that she had developed lockjaw after one dose of prochlorperazine during
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.
Vol. 45 No. 5 May 2013
6. National Quality Forum. A national framework and preferred practices for palliative and hospice care quality. 2006. Available from http://www.qualityfo rum.org/Publications/2006/12/A_National_Frame work_and_Preferred_Practices_for_Palliative_and_ Hospice_Care_Quality.aspx. Accessed January 29, 2013. 7. Niraula S, Seruga B, Ocana A, et al. The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol 2012;30:3012e3019. 8. Rehman S, Baka S, Lau S, et al. A review of the treatment strategies for small cell lung carcinoma patients with a poor performance status. Curr Respir Med Rev 2006;2:59e66. 9. Ahn HK, Jeon K, Yoo H, et al. Successful treatment with crizotinib in mechanically ventilated patients with ALK positive non-small-cell lung cancer. J Thorac Oncol 2013;8:250e253. 10. Lee SM, Khan I, Upadhyay S, et al. First-line erlotinib in patients with advanced non-smallcell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2012;13:1161e1170. 11. Park K, Tsai CM, Ahn MJ, et al. ASPIRATION: phase II study of continued erlotinib beyond RECIST progression in Asian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). [Abstract]. J Clin Oncol 2012;30(Suppl; abstr TPS7614). Available from http://www.asco.org/ASCOv2/Meetings/ Abstracts?&vmview¼abst_detail_view&confID¼114& abstractID¼98869. Accessed January 26, 2013.
Locked-In Syndrome as a Result of Cyclizine Administration To the Editor: Movement disorders, including akathisia, dystonia, and tardive dyskinesia, resulting from the use of antiemetic medications are not uncommon side effects in the palliative care setting. There have been a number of case reports of severe acute dystonic reactions after single doses of cyclizine1e4 and of transient paralysis also after single doses of cyclizine.5,6 Previously, the author has personally recognized only one movement disorder case after administration of cyclizine, a 78-year-old man with metastatic non-small cell lung cancer who developed tardive dyskinesia after taking oral cyclizine 25 mg three times a day for one week. The following case describes the
Letters
e5
development of locked-in syndrome one month after starting cyclizine.
Case A 24-year-old woman was diagnosed with bilateral serous papillary adenocarcinoma Stage IIIc in 2008. She underwent bilateral salpingooophorectomy, debulking, and omentectomy followed by multiple lines of chemotherapy. Her progress was complicated by recurrent small bowel obstructions, and her care was transferred to the palliative care team for supportive care in November 2012. She was admitted to the palliative care ward in early December 2012 with a malignant bowel obstruction characterized by feculent vomiting, absolute constipation, abdominal pain, and nausea. This settled with conservative management, and she was discharged home on a subcutaneous infusion of fentanyl 600 mcg and octreotide 300 mcg over 24 hours, subcutaneous cyclizine 25 mg twice a day, and intermittent subcutaneous fluids as requested by the patient and family, approximately 500 mL daily. The patient was managed at home by her family with support from the community palliative care team. Over the course of the following 30 days, she had intermittent vomiting episodes and pain. Fentanyl was titrated up to 900 mcg over 24 hours, octreotide to 600 mcg, and cyclizine to 25 mg three times a day. In early January 2013, she had another episode of feculent vomiting and then became unresponsive. The patient had expressed the wish to be admitted to the palliative care unit for her end-of-life care and her family arranged admission. She received intravenous fluids to see if rehydration would improve her condition, and fentanyl, octreotide, and cyclizine were continued at the same doses. She had no further vomiting and remained unresponsive, with her family and the staff expecting that she would soon die. After 72 hours of admission, it was noted by the medical staff that the patient’s eyes were open and she was following. She was unable to speak, move, or blink spontaneously or on command. The nursing staff reported that they were unable to administer mouth care because she was ‘‘biting down.’’ On questioning, her family reported that she had developed lockjaw after one dose of prochlorperazine during