Pharmacological and clinical aspects of immediate release fentanyl preparations: Criteria for selection

In palliative care, pain management is often hampered by episodes of breakthrough pain, characterised by a rapid onset and, on average, duration less than 1 h. Until recently, only immediate release morphine and oxycodon preparations were available for the treatment of these episodes but time until effect is too long for both of these drugs. Recently, immediate release fentanyl products have become available for the treatment of breakthrough pain. These products can be classified as oromucosal and nasal products. Both are absorbed rapidly by the mucosa, although the oromucosally delivered products are partly absorbed by the gastrointestinal tract and therefore reach maximum plasma levels somewhat slower (after 30-90 min) than the nasally delivered products (after ~15 min). In clinical placebo controlled studies, all new immediate release fentanyl products were proven to be effective from 15 min after administration in the treatment of breakthrough pain. The first studies comparing immediate release fentanyl with immediate release morphine or oxycodon also found superiority for the new fentanyl products

Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

Purpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Methods: Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. Results: A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h-1, respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. Conclusions: We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic:A retrospective population-based study

Background: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. Aim: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. Design: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, &gt;1 emergency room contact, &gt;1 hospitalization, hospitalization &gt;14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. Participants: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. Results: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74–0.88 and OR 0.92; 95% CI 0.87–0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. Conclusions:Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.</p

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic:A retrospective population-based study

Background: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. Aim: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. Design: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, &gt;1 emergency room contact, &gt;1 hospitalization, hospitalization &gt;14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. Participants: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. Results: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74–0.88 and OR 0.92; 95% CI 0.87–0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. Conclusions:Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.</p

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic:A retrospective population-based study

Background: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. Aim: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. Design: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, &gt;1 emergency room contact, &gt;1 hospitalization, hospitalization &gt;14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. Participants: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. Results: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74–0.88 and OR 0.92; 95% CI 0.87–0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. Conclusions: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.</p

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p