Journal of Oncology Pharmacy Practice最新文献

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.

Introduction: Intravenous (IV) medications can be prepared using compounding devices to increase productivity, and reduce risks associated with aseptic compounding. This study evaluated the productivity and quality outcomes of the aseptic process for simulated batches of IV medications used in clinical practice produced using a semi-automated compounding device (Gri-fill; Grifols).

Methods: Simulated batches from 50 to 600 preparations were completed representing hazardous and non-hazardous drugs, including one-step single component (atropine sulfate, cisplatin) and multistep, multiple component (mitomycin C, piperacillin/tazobactam, trastuzumab, 5-fluorouracil and gemcitabine). Productivity, device autonomy, quality of the aseptic process (media-fill test) and sterility of the preparations were evaluated.

Results: A total of 2024 final preparations and 460 intermediate products were compounded during 78 working hours. For low and high complexity level preparations, median (minimum-maximum) production speed was 1.3 (0.6-1.7) and 3.7 (2.6-4.3) min per preparation, respectively. The longest process (36.2 min/bag) was the preparation of a simulated gemcitabine 3 L bulk solution bag, which included reconstitution of vials and filling the bulk bag. All operational errors (0.6%) were resolved autonomously by the user. None of the 883 media fill preparations showed microbiological growth and all 114 analyzed preparations passed the sterility test.

Conclusions: Using a semi-automated compounding device, preparation efficiency of IV medications ranged from 14 preparations/h for multicomponent preparations from vials requiring reconstitution, to 100 preparations/h for low complexity preparations using a bulk solution bag. The aseptic processes demonstrated the absence of microbial growth in all tested preparations.

Introduction: Treatment advances for hematologic malignancies (HM) have dramatically improved life expectancy, necessitating greater focus on long-term cancer pain management. This study explored real-world patterns of opioid use among patients with HM.

Methods: This retrospective cohort study identified adults diagnosed with HM from January 1, 2013 through December 31, 2019 using the Truven MarketScan Commercial Claims and Encounters database. Across several HM types, we described rates of high-risk opioid use (based on Pharmacy Quality Alliance measures) and opioid-related harms, including incident opioid use disorder (OUD) diagnoses and opioid-related hospitalizations or emergency department (ED) visits. We used multivariable Cox regression to generate adjusted hazard ratios and 95% confidence intervals comparing the risk of opioid-related harms between patients with versus without high-risk opioid use.

Results: Our sample included 43,190 patients with HM. Median age at HM diagnosis was 54 years (interquartile range  =  44-60). Most patients (61.9%) were diagnosed with lymphoma. Approximately half (49.2%) had an opioid dispensed in the follow-up period. Among all patients, 20.0% met criteria for high-risk opioid use, 0.9% had an OUD diagnosis, and 0.3% experienced an opioid-related hospitalization/ED visit in follow-up. High-risk opioid use increased the risk of an OUD diagnosis by 3.3 times (p < 0.0001) and an opioid-related hospitalization/ED visit 4.2 times (p < 0.0001).

Conclusion: High-risk opioid use was prevalent among patients with HM and significantly increased the risk of opioid-related harms. However, rates of opioid-related harms were low. These findings highlight the importance of continually monitoring pain and opioid use throughout HM survivorship to provide safe, effective HM pain management.

Introduction: To date, there is no adherence estimator to identify risk of nonadherence prior to initiating oral oncolytics.

Methods: A workgroup was assembled through the National Community Oncology Dispensing Association and tasked with creating a tool to meet this need. Tool constructs were defined after a review of the literature identifying top barriers to adherence. A second literature search was conducted to identify questions targeting specific barriers from validated adherence questionnaires. Once a finalized draft was complete, the risk assessment tool was built into an electronic survey where a risk category can be automatically calculated for the patient.

Results: The six most impactful factors affecting compliance to oral oncolytics were identified as patient's confidence, health literacy, perception of treatment, quality of life, social support, and complexity of chemotherapy regimen. A six-item questionnaire was created with five patient-directed questions and one clinician-directed question. Examples and descriptions were provided for clinicians to consider when categorizing complexity of a regimen. The tool was designed for responses to each question to be indexed into categories through a 10-point system. Results will be stratified into low, moderate, or high risk for nonadherence.

Conclusion: The creation of a tool to predict nonadherence prior to starting therapy is an unmet need for patients initiating oral oncolytics. The aim of this tool is to meet those needs and better guide clinicians to provide patients with strategies to better manage nonadherence. Next steps include tool validation and piloting in clinical practice.

Introduction: Pembrolizumab is a monoclonal PD-1 inhibitor used in the treatment of lung cancer in addition to several other malignancies. Psoriasiform dermatitis is a well-documented adverse effect.

Case report: We present a 68 year-old-male with a 50-year smoking history and a 30-year remote history of plaque psoriasis, limited to the knees and elbows, who presented with metastatic non-small cell lung cancer. He was started on a chemotherapy regimen of carboplatin, paclitaxel, and pembrolizumab. One month later, he presented to dermatology with diffuse erythematous scaly papules coalescing into plaques on 80% of body surface area (BSA).

Management & outcome: Pembrolizumab treatment was paused. The patient was prescribed triamcinolone 0.1% twice daily, but still had significant BSA at one-month and was started on an Il-17 inhibitor, ixekizumab, clearing the psoriasiform dermatitis. He was rechallenged with pembrolizumab every 3 weeks and repeat PET/CT demonstrated excellent tumor response.

Discussion: This case prompted a literature review to further characterize the use of IL-17 inhibitors for psoriasiform dermatitis in the setting of ICI therapy. All six cases demonstrated improvement of psoriasiform dermatitis, with two cases showing partial response and four cases showing complete resolution. In three of the six cases, the patients exhibited clinical response to the primary malignancy after rechallenging with ICI, while remaining on an IL-17 inhibitor. Our case, in conjunction with the other reported cases, seems to suggest that IL-17 blockade can maintain a fine balance in this challenging clinical scenario by treating psoriasiform dermatitis without compromising the efficacy of immunotherapy.

Background: With the recent Food & Drug Administration (FDA) approval of cellular therapy that requires product manipulation prior to administration in combination with a short stability window, the need was identified for local dose preparation within the pharmacy rather than the off-site stem cell processing laboratory. This approval gave rise to assessment of regulatory standards surrounding cellular therapy, evaluation and revision of current standard operating procedures and policies with formal process validation, assessment of occupational exposure mitigation and safety considerations, and development of staff training and education.

Objective: To describe and provide insight into the stepwise process of FACT validation and onboarding of commercially available cellular therapy products that require sterile compounding manipulation within a pharmacy prior to administration.

Discussion: A multidisciplinary effort is required to attain FACT certification and implement pharmacist compounding of cellular therapy products.¹ Local preparation within a pharmacy facilitates a sound operational workflow and provides a pathway to perform aseptic manipulations of cellular therapy products safely and efficiently.

Conclusion: Safe and successful administration of cellular therapies handled and compounded by pharmacy department staff along with program validation requires a preemptive review utilizing a multidisciplinary approach for process development. This manuscript will provide a foundation based on consistency and transparency in effective cellular therapy sterile compounding and aseptic manipulation, proper handling and disposal procedures, increased communication through creation and optimization of treatment plans and order-sets, standardized medical center staff education, and development of policies and standard operating procedures for the entire health care team.

Objective: Dostarlimab, a humanized monoclonal PD-1 blocking antibody, is being tested as a cancer therapy in this review. Specifically, it addresses mismatch repair failure in endometrial cancer and locally progressed rectal cancer patients.

Data sources: A thorough database search found Dostarlimab clinical trials and studies. Published publications and ongoing clinical trials on Dostarlimab's efficacy as a single therapy and in conjunction with other medicines across cancer types were searched.

Data summary: The review recommends Dostarlimab for endometrial cancer mismatch repair failure, as supported by GARNET studies. The analysis also highlights locally advanced rectal cancer findings. In the evolving area of cancer therapy, immune checkpoint inhibitors including pembrolizumab, avelumab, atezolizumab, nivolumab, and durvalumab were discussed.

Conclusions: Locally advanced rectal cancer patients responded 100% to Dostarlimab. Many clinical trials, including ROSCAN, AMBER, IOLite, CITRINO, JASPER, OPAL, PRIME, PERLA, and others, are investigating Dostarlimab in combination treatment. This research sheds light on Dostarlimab's current and future possibilities, in improving cancer immunotherapy understanding.