Journal of Oncology Pharmacy Practice最新文献

Objective: Despite significant advances in cancer treatment with targeted therapies and immunotherapies, cytotoxic chemotherapies are still extensively used. Potential cytotoxic contamination in preparing and administrating cytotoxics is still a major source of concern. Besides advanced protections including biological safety cabinets, work surface contamination needs to be continuously controlled to ensure that handling procedures and cleaning were appropriate. Contamination monitoring needs to be standardized.

Data sources: The study searched Pubmed/Medline and Embase with"hazardous drug", "cytotoxic drug", "surface contamination", "environmental contamination", "wipe sample", "pharmacy", "care unit", and selected studies reporting contamination results in work environment for pharmacy technicians and nurses, from 1 January 2017 to 31 December 2022.

Data summary: The 29 studies totalized 16,196 samples and 189,571 assays. Contamination results showed 39.8% sample positivity, and 8.2% assay positivity. Multicentric studies gathering at least 500 samples or up to 800 samples would limit heterogeneity in sample positivity. In addition, monitoring of an appropriate tracer selection including at least the 7 tracers with the highest contamination frequencies (cyclophosphamide, gemcitabine, fluorouracile, ifosfamide, platinum derivatives, paclitaxel and methotrexate) would facilitate contamination comparisons amongst studies and local results. Most recent studies reported thresholds for cyclophosphamide close to 0.1 ng/cm² at the 90^th percentile.

Conclusions: The overall risk of exposure for healthcare professionals is a major concern. Sample size in multicentric studies would require at least 500 samples; quantification of all tracers with the highest contamination frequencies need to be quantified. This approach would provide a basis to develop guidelines to appropriately monitor contamination in pharmacies and patient care area managers.

Introduction: Mutated rearranged during transfection (RET) kinase is found in approximately 1-2% non-small-cell lung cancer (NSCLC) patients. These patients are typically younger, non-smokers, and have non-squamous histology. Pralsetinib is a novel RET inhibitor that showed promising efficacy and tolerability in the ARROW trial. Due to the small percentage of patients that have RET mutated NSCLC, real world data on safety is still needed.

Case report: This case report outlines a patient who was initiated on pralsetinib for RET mutated NSCLC and subsequently developed reactivation of cytomegalovirus (CMV) viremia and hepatitis B.

Management and outcome: The patient was initiated on valganciclovir and entecavir with subsequent improvement in viral loads. They were able to reinitiate pralsetinib at a lower dose following improvement of CMV and hepatitis B viral load with continuation of entecavir.

Discussion: RET is responsible for activation of several signaling paths including PI3K/AKT and JAK/STAT. Those pathways are involved in the immune system. When reviewing current JAK inhibitors and PI3K inhibitors on the market, there is mixed data on HBV reactivation and CMV viremia, though theoretically possible. Therefore, this should be evaluated and addressed in further studies. The educational value of this case could provide valuable insights for baseline monitoring and management for similarly effected patients.

Introduction: Exposure of healthcare workers to hazardous drugs may result in adverse health effects underscoring the importance of validating working procedures and safety precautions to minimise the risk. The objective was to monitor environmental contamination caused by the hazardous drug workflow: from drug vials, compounding process, to patient administration.

Methods: Surface wipe samples were collected from potentially contaminated surfaces in the compounding department and in the administration department. The outside of drug vials, compounded syringes, bags, elastomeric pumps, and gloves used by the nurses for administration were also monitored. Stationary air samples were collected near the isolators and above the bench top. Personal air samples were collected from pharmacy technicians, pharmacists, and nurses. Monitoring was performed in three trials during two-months. Samples were analysed for cyclophosphamide, 5-fluorouracil, docetaxel, and paclitaxel using liquid chromatography tandem mass spectrometry.

Results: Contamination was mainly found for 5-fluorouracil and cyclophosphamide on isolator surfaces, bench top, trays, and compounded products. Lower levels of contamination were measured in the administration department on trays, trolley arms and gloves of the nurses. Paclitaxel and docetaxel were incidentally detected. Air contamination was found for paclitaxel in the compounding department in one trial, and 5-fluorouracil was detected once in front of an isolator. Docetaxel was found in one air sample of a nurse.

Conclusions: Contamination was mainly found for 5-fluorouracil and cyclophosphamide on the products compounded in the isolators. Contamination was further spread along the workflow towards the administration department causing surfaces in between being contaminated too.

Introduction: The purpose of this study was to assess and compare the effectiveness of seven different closed system transfer device (CSTD) product lines following the 2015 NIOSH Vapor Containment Performance Protocol, using a Gasmet™ DX5000 Terra multigas FTIR analyzer.

Methods: Seven different CSTD systems were assessed using a two-task evaluation on their capacity to contain the NIOSH-specified challenge agent, 70% isopropyl alcohol (IPA). Task 1 simulated reconstitution and compounding steps while Task 2 simulated compounding and administration steps. Vial adapters, syringe adapters, IV bag adapters, and y-site adapters from each CSTD product line were tested. All tasks were performed in a custom-built environmental test chamber as outlined in the 2015 NIOSH protocol, with isopropyl alcohol (IPA) release detected and measured by a Gasmet™ analyzer.

Results: The BD PhaSeal™ CSTD product line effectively contained IPA vapor during both tasks with a task performance metric of 0.00 ppm for each task. BD PhaSeal™ Optima, Equashield^®, Yukon Medical Arisure^®, ICU Medical ChemoLock™, BD Texium™, and ICU Medical ChemoClave™ non-vented CSTDs demonstrated detectable and quantifiable IPA leakage during each task. The leaks occurred at different steps within the protocol, and the amount of IPA vapor detected varied.

Conclusion: In this study, one CSTD product line (i.e., PhaSeal™) successfully contained IPA vapor below the Gasmet™ analyzer's limit of quantification (LOQ) for IPA of 0.04 ppm for both Tasks 1 and 2, demonstrating it to be a validated closed system per the study protocol. All other CSTD product lines demonstrated some level of IPA leakage with task performance metrics above the analyzer's LOQ. However, these results tell us little about how well CSTDs contain hazardous drugs (HDs), as a universal HD surrogate for effectively assessing the closedness of all types of CSTDs has yet to be identified.

Background: Previous research has shown community pharmacists do not have high perceived competence or confidence providing care to patients on oral anti-cancer medications. There is a paucity of evidence when it comes to hospital pharmacists providing care to oncology patients admitted to the hospital for a reason other than cancer.

Objective(s): To assess the perceived competence of hospital pharmacists not working in oncology in managing patients taking anticancer drugs. Additionally, identify factors impacting, potential interventions increasing, and any factors that improve perceived competence.

Methods: An anonymous cross-sectional survey distributed to hospital pharmacists throughout Canada.

Results: Mean perceived competence results ranged from 2.52 to 3.97 out of 7.00 with respondents reporting most perceived competence managing electrolyte disturbances and least competence managing drug-disease interactions and intervening on hepatic dysfunction. Low confidence in knowledge received from previous oncology training was reported with a mean of 2.82 on the 7-point Likert Scale. Continuing education sessions were perceived as the intervention which would most improve perceived competence with a mean value of 5.92 to 5.94 on a 7-point Likert Scale. The number of CE hours completed in the last five years was the only factor shown to have a statistically significant correlation with perceived competence.

Conclusion: Hospital pharmacists do not perceive themselves as competent in providing care to oncology patients. The implementation of a continuing education program related to oncology may improve perceived and actual competence.

Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) and are now used in both early-stage and metastatic disease. Recent case reports suggest that pseudo-serum creatinine (Scr) elevations are likely a class effect of CDK4/6i.

Methods: This single-center retrospective analysis included patients aged ≥18 years who received at least one dose of palbociclib, ribociclib, or abemaciclib for the treatment of HR+/HER2- BC in the early or advanced setting. The primary objective was the incidence of pseudo-Scr elevation for each of the three agents. CDK4/6i-induced pseudo-Scr elevation was suspected when the Scr elevation could not be fully attributed to other causes. Secondary endpoints included the grade, onset, duration, and clinical consequences of pseudo-Scr elevation.

Results: 143 patients were included. Pseudo-Scr elevation was suspected in patients treated with palbociclib, ribociclib, or abemaciclib, with incidences of 16% (8/50), 14% (6/43), and 20% (10/50), respectively. Rates did not significantly differ between agents (p = 0.727). Among patients with CDK4/6i-induced pseudo-Scr elevation, all events were grade 1 (8.3%) or 2 (91.7%). The median onset from treatment initiation to first Scr elevation was 33.5, 42, and 21.5 days, for palbociclib, ribociclib, or abemaciclib, respectively.

Conclusion: Pseudo-Scr elevation appears to be a class effect of CDK4/6i, with similar rates of Scr elevation observed across the three agents currently FDA approved.

Background: Standard treatment for bone metastases is based on bisphosphonates such as zoledronic acid. The objective of this study was to evaluate the incidence of acute renal failure during treatment with Zoledronate and to analyze its correlated factors.

Materials and methods: This is a retrospective study carried out at the medical oncology department of Habib Bourguiba University Hospital in Sfax, between January 2022 and March 2022. The creatinine dosage was carried out using the Jaffe-type colorimetric method. Acute renal failure was defined by the Kidney disease Improving Global Outcomes criteria.

Results: 48 patients were included. The average age was 56.9 ± 10.7 years with a sex ratio (M/F) equal to 0.5. The average weight of the patients was equal to 68.5 ± 16.4 kg. 62.5% of patients were followed for breast cancer, 12.5% had lung cancer and 12.5% had prostate adenocarcinoma. The mean serum creatinine before the start of treatment was equal to 74.3 ± 34.3 µmol/l 50.84 ± 0.11 mg/dl). The mean pre-therapeutic clearance was 94.1 ± 40.2 ml/min with 4 cases of moderate renal impairment (8.3%). Acute renal failure according to KDIGO during treatment with Zoledronic acid was observed in 9 cases (18.8%), thus requiring a dose reduction. Acute renal failure was significantly associated initial clearance <60 ml/min and low weight of 53.44 kg (p = 0.003 and p = 0.01 respectively), in multivariate analysis.

Conclusion: Our study concluded that factors associated with acute renal failure were low weight and clearance less than 60 ml/min.

Introduction: Frontline therapy for patients with advanced cutaneous melanoma often includes immune checkpoint inhibitors (ICIs). Although these agents have increased response rates, many patients will experience immune-related adverse events (irAEs). The difference in safety profiles of the current combinations available are not well established. Therefore, this study aimed to compare the incidence of severe irAEs of patients receiving ipilimumab-nivolumab versus nivolumab-relatlimab in a real-world setting.

Methods: A retrospective chart review was conducted on all patients who underwent treatment with either combination ICI for advanced cutaneous melanoma.

Results: A total of 47 patients who received either one or more doses of either combination ICI were included for analysis. Of these patients, 37 (78.2%) had at least one irAE of any grade. The baseline characteristics among the patients who received nivolumab-relatlimab and those who received ipilimumab-nivolumab were not significantly different. The severity of the 73 irAEs that occurred ranged from grade 1 to grade 3, with 16 (21.9%) irAEs occurring in the nivolumab-relatlimab, 3 (18.8%) of which were grade 3-4. Meanwhile, those receiving ipilimumab-nivolumab developed 57 (78.1%) irAEs, with 14 (24.6%) being grade 3-4. This study's findings show that nivolumab-relatlimab had a lower incidence of developing severe irAEs in comparison to ipilimumab-nivolumab.

Conclusions: Treatment with nivolumab-relatlimab could be preferred as a combination ICI given the lower incidence of severe irAEs, delayed onset of irAEs, and lower rate of treatment discontinuation.

Introduction: The multikinase inhibitor midostaurin is the first targeted drug for the treatment of AML FLT3. It reduces mortality by 23% more than standard chemotherapy group. Although it has many gastrointestinal side effects, there is no data in the literature regarding its association with acute pancreatitis. We wanted to present an acute pancreatitis case that developed after midostaurin treatment in our clinic.

Case report: A patient with AML FLT3 who developed abdominal pain, elevated amylase-lipase enzymes and increased volume around the pancreas on abdominal imaging after the addition of midostaurin to chemotherapy was hospitalized with a prediagnosis of acute pancreatitis.

Management & outcome: Oral feeding was stopped, intravenous hydration was provided and anti-symptomatic treatment was given. The patient was discharged on the 4th day of hospitalization after the acute pancreatitis clinic resolved.

Discussion: Drug induced acute pancreatitis is a rare clinical condition which is difficult to diagnose. It has a good prognosis and low mortality rate. The mechanisms of drug-induced pancreatitis include immunological reactions, direct toxic effect, accumulation of toxic metabolites, overstimulation of pancreatic acinar cells, ischemia, intravascular thrombosis and increased viscosity of pancreatic secretion. Although there are many gastrointestinal side effects of midostaurin, there are no clear data in the literature regarding the relationship with acute pancreatitis.

Introduction: A hypoxic tumor microenvironment inhibits the normal functioning of immune cells. Studies have hypothesized that anticoagulants that can penetrate and bind to factor Xa in the tumor microenvironment, can enhance T-cell function and augment immunotherapy activity. This study compared objective response rate and progression-free survival of lung cancer patients on concomitant immunotherapy treated with direct-acting oral anticoagulants versus enoxaparin.

Methods: This single-center retrospective study included 73 adults with stage-IV lung cancer who received at least two cycles of immunotherapy and one month of anticoagulant therapy with direct-acting oral anticoagulants (Arm A) versus enoxaparin (Arm B) between June 1, 2016, to September 30, 2022. Primary endpoint was objective response rate, and secondary endpoints were rates of complete response, progression-free survival, incidence of thrombotic events, and major bleeding.

Results: Objective response rate at 6 months was 24.5% versus 25% while progression-free survival at 6 months was 54.7% versus 45% in Arm A versus Arm B, respectively. Complete response rates at 6 months were 7.5% in Arm A versus 0% in Arm B. One patient in Arm A and two in Arm B had a recurrent deep vein thrombosis. Nine patients in Arm A and two in Arm B were diagnosed with new deep vein thrombosis. One patient in Arm B was diagnosed with new pulmonary embolism. Two major bleeding events occurred in Arm B.

Conclusions: Our study suggests a trend toward improved progression-free survival at 6 months with no new safety concerns in lung cancer patients on concurrent immunotherapy and direct-acting oral anticoagulants.