Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference −4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference −3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event

Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

[Purpose] A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. [Methods] We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. [Results] Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS-defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. [Conclusion] Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions

Eating-related distress and need for nutritional support of families of advanced cancer patients: A nationwide survey of bereaved family members

Background: A number of advanced cancer patients are suffering from physical and psychosocial burdens because of cancer cachexia, and these burdens also greatly impact on their family members and relationships between patients and family members. It is necessary to consider the psychosocial impact of cancer cachexia on family members of advanced cancer patients. Methods: A cross-sectional anonymous nationwide survey was conducted involving 925 bereaved family members of cancer patients who had been admitted to 133 inpatient hospices throughout Japan. Results: A total of 702 bereaved family members returned the questionnaires (response rate, 75.9%). Concerning eating-related distress, 'I served what the patient wanted without consideration of calories and nutritional composition' was highest (75.1%), and 'I tried making many kinds of meals for the patient' and 'I was concerned about planning meals for the patient every day' followed (63.0% and 59.4%, respectively). The top 5 of the 19 items were categorized as 'fighting back'. Need for nutritional support was high (72.2%), and need for explanations about the reasons for anorexia and weight loss of patients was moderate (41.4%). Explanatory factor analysis of eating-related distress identified the following four domains: (factor 1) feeling that family members forced the patient to eat to avoid death, (factor 2) feeling that family members made great efforts to help the patient eat, (factor 3) feeling that eating was a cause of conflicts between the patient and family members, and (factor 4) feeling that correct information was insufficient. Results of multiple logistic regression analysis showed that spouse, fair/poor mental status, factors 1, and 4 were identified as independent determinants of major depression (odds ratio [OR] 3.27 [95% confidence interval (CI) 1.24-8.60], P=0.02; OR 4.50 [95% CI 2.46-8.25], P<0.001; OR 2.51 [95% CI 1.16-5.45], P=0.02; OR 2.33 [95% CI 1.13-4.80], P=0.02, respectively). Conclusions: A number of family members of advanced cancer patients experienced high levels of eating-related distress and had a need for nutritional support

A survey of practice in management of malignancy-related ascites in Japan.

Although ascites is a distressing complication observed commonly in the course of advanced cancer, there is no effective treatment established for malignancy-related ascites. We conducted a nationwide survey of cancer physicians in Japan who treat malignancy-related ascites in order to determine what kind of therapeutic approach is thought to be significant and what kind of diuretic prescriptions are thought to be standard for malignancy-related ascites. From 2017 to 2018, we sent a one-page memo to oncologists in Japan asking them to participate in a questionnaire-style survey that they could complete online. The significance of each of the nine representative interventions was measured on a 5-stage Likert scale. At the same time, participants were asked about what type and dosage of diuretics they thought to be standard as a treatment for malignancy-related ascites. Ultimately, 187 oncologists responded to our invitation. The interventions that were particularly significant were reducing hydration volume, paracentesis, and symptom management with analgesics. The respondents indicated that the importance of diuretics was significantly lower than that of these three interventions. Furthermore, 86.2% of the respondents in Japan regarded the use of loop diuretics ± aldosterone antagonists as the standard of diuretic therapy for malignancy-related ascites, and the most common regimen was 20 mg of oral furosemide ± 25 mg of spironolactone daily at the start, and 30-40 mg ± 50 mg daily at the time of initial escalation. Although our study revealed that the attitude of oncologists in Japan toward therapeutic options for malignancy-related ascites was nearly consistent with that of previous reports from other countries, it was newly found that they seemed to commonly be concerned with preventing overhydration of terminally ill cancer patients and that analgesics were also thought to be a significant form of intervention

Psychological Distress among Caregivers for Patients Who Die of Cancer: A Preliminary Study in Japan

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Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference −4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference −3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event

Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

PURPOSE: A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. METHODS: We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)‐defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia‐modified Karnofsky PS ≥50. RESULTS: Among 1896 patients, the incidence of rapid decline death was the highest (30‐day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS‐defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. CONCLUSION: Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions