Journal of Oncology Pharmacy Practice最新文献

Aim/background: The aim of this study was to determine long-term physicochemical and biological stability of nivolumab and pembrolizumab diluted in saline infusion bags and partially used medication vials. This may enable the prolonged clinical use of these expensive monoclonal antibodies (mAbs) to minimize the economic loss.

Methods: Sterile nivolumab and pembrolizumab concentrates in partially used medication vials and compounded nivolumab and pembrolizumab infusion solutions were stored for two and four weeks, respectively, at 2-8°C in the dark. Subsequently, concentrates and compounded solutions were stored for an additional two weeks under ambient temperature and light conditions. A panel of validated and complementary methods, consisting of enzyme-linked immunosorbent assay, size exclusion chromatography, and dynamic light scattering, were used to assess the biological and physiochemical stability of these mAbs.

Results: All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. Diluted in infusion bags, nivolumab and pembrolizumab remained biologically and physiochemically stable for up to four weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light. Stability in partially used medication vials was demonstrated for at least two weeks when stored at 2-8°C in the dark with an additional two weeks of ambient temperature and light.

Conclusion: The findings of this study justify the storage and clinical re-use of sterile nivolumab and pembrolizumab in partially used medication vials and compounded IV infusion bags for up to six weeks. This minimizes the risk of economic loss due to waste. Moreover, these findings support the batch-wise compounding of fixed-dose and dose-banded nivolumab and pembrolizumab infusion bags.

Objective: To provide a rationale for a collaborative care model involving oncology and primary care pharmacists to improve the coordination of care of medications for cancer patients with multiple chronic conditions.

Data sources: A review of selected literature and the authors' own research was used. Studies illustrating the gaps in care for medications and pharmacists' roles in oncology and primary care settings from PubMed were reviewed.

Data summary: There has been a substantial increase in the development and utilization of oral anticancer agents (OAAs). Although OAAs offer convenience and flexibility, they also introduce challenges related to medication adherence, monitoring, and managing side effects. Up to 17.5% of patients experience moderate to severe symptoms from OAAs and about 30% report less than excellent medication adherence. Further, studies showed that 30% to 53% of adult cancer patients have at least one chronic condition that complicates their treatment plan due to the need for medications, increasing the risk of drug interactions, side effects, and non-adherence. The Primary Care Oncology Model (PCOM) incorporates both primary care and oncology pharmacists with comprehensive medication review and patient-reported outcome measure, respectively, to enhance medication appropriateness and effectiveness, and improve overall patient experience.

Conclusion: Implementing PCOM may improve the medication management of patients taking OAAs for active cancer treatment and chronic medications for their multiple chronic conditions. This collaborative approach can transform patient care by leveraging the expertise of both primary care and oncology pharmacists.

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.

Introduction: Breast cancer, the most prevalent cancer among women, often requires chemotherapy with docetaxel being a key agent. However, docetaxel-inducted peripheral neuropathy (DIPN) can adversely impact patients' quality of life. This case discusses an unusual instance of severe DIPN leading to wheelchair dependence in a 35-years old woman undergoing neoadjuvant treatment for locally advanced breast cancer.

Case: Following anthracycline and cyclophosphamide cycles without neurological symptoms, docetaxel administration resulted in progressive neuropathy. Despite dose reduction, the patient developed severe paraesthesias, foot weakness, and eventually wheelchair dependence.

Management and outcome: Docetaxel's microtubule-stabilizing mechanism, vital for cell division, may disrupt axonal structures, causing sensory and motor neuropathy. While rare, severe motor neuropathy, leading to wheelchair dependence, poses a significant challenge. The frequency of DIPN varies, with docetaxel exhibiting lower neuropathy rates than other taxanes. Risk factors include age, diabetes mellitus, cumulative dose, and genetic polymorphisms in GSTP1 and ABCB1. In our case, despite the patient being young, fit and without diabetes, severe DIPN occured, suggesting a potential genetic predisposition. Genetic variations, such as GSTP1 polymorphisms have been associated with DIPN. Our patient carried GSTP1 (I1e105Val) mutations, emphasizing the need for further research to establish their role as risk factors.

Discussion: This case underscores the importance of recognizing severe DIPN, even in atypical patient profiles. Genetic factors, like GSTP1 polymorphisms, may contribute to DIPN risk. Large-scale studies are crucial to establishing the significance of these genetic variations in DIPN susceptibility.

Introduction: Opioid medications are crucial for managing pain among patients with cancer. Yet, inappropriate prescribing and medication issues can compromise patient safety and quality of care. Clinical pharmacists play a significant role in optimizing opioid therapy and addressing issues related to opioid medication use.

Objectives: This study aimed to examine clinical pharmacist interventions and identify opioid medication-related issues in patients with cancer.

Method: We conducted a retrospective observational study at Shaukat Khanum Memorial Cancer Hospital and Research Center in Lahore, Pakistan, conducting a chart review from 1^st July 2021 to 31^st December 2021.

Results: Out of 10,534 opioid medication orders, we documented a total of 974 interventions based on our inclusion criteria. Tramadol and morphine accounted for most of these interventions, comprising 49.27% (n = 475) and 40.04% (n = 386), respectively. Regarding clinical significance, 41.70% (n = 406) were deemed significant, while 37.36% (n = 365) were somewhat significant. The majority of interventions, i.e., 54.05% (n = 521), primarily aimed at optimizing patient outcomes, followed by a secondary aim of improvements in communication, i.e., 25.52% (n = 246).

Conclusion: This study establishes the evaluation of clinical pharmacist interventions on opioid medication use in patients with cancer, an issue particularly in oncology settings in Pakistan. The findings emphasize the crucial role of clinical pharmacists in addressing issues related to opioid issue medications, thus improving patient safety and optimizing opioid use for patient well-being.

Introduction: Taxanes and platinum are first-line treatments in gynecological tumors with high rates of hypersensitivity reactions (HSRs), leading to discontinuation of treatment. Desensitization involves induction of temporary tolerance to previously sensitized medications. The aims of this study are to describe HSRs to paclitaxel and carboplatin and evaluate the safety and effectiveness of desensitization protocols in gynecological cancer patients.

Methods: Original, retrospective, descriptive, analytical study, approved by Bioethics and Research Committee, included >18-year-old patients with gynecological tumors experiencing HSRs to first-line chemotherapy. Patients underwent 3-bag-12-step desensitization.

Results: 174 desensitization (95 paclitaxel, 79 carboplatin) in 33 female patients, mean age 45.5 years (18-71y). Cancer diagnosis: breast 8 (24.2%), ovarian 14 (42.2%), endometrial 2 (6.1%) and cervix 9 (27.2%). HSR occurred in paclitaxel during cycles 1-2 and in carboplatin after 6 cycles. The most frequently seen HSR symptom was cardiovascular with paclitaxel (94.7%), and cutaneous (93.3%) with carboplatin. Three-bags 12-steps desensitization protocol (initial dilution 1:100) in 5.67hrs. All patients reached total dose desensitization: 82% with no reaction, 12% mild, 6% moderate and 0% severe reaction. Mean disease-free interval and progression-free interval in months (m): breast cancer 29 m and 14 m, ovarian 22 m and 9 m, endometrial 40 m and cervical cancer: 67.5 m and 27 m. Twenty-five patients (73.5%) are still alive.

Conclusion: HSRs to paclitaxel manifest in the first 1-2 cycles and to carboplatin after 6 cycles. Symptoms include cardiovascular, atypical neuromuscular and urticaria. Changing treatment lines impacts prognosis. Our study revealed that ovarian cancer patients undergoing desensitization protocols achieved longer progression-free intervals. All patients successfully reached total dose desensitization. This study provides evidence of the effectiveness and safety of desensitization and promising perspective for continuing first-line treatment with HSRs.

Introduction: The role of genetic variants in response to chemotherapy has been investigated in several studies. This study aimed to investigate genetic variants associated with response to chemotherapy in breast cancer (BC) patients. Methods: Significant variants (p < 5 × 10^-8) associated with response to chemotherapy were obtained from GWA studies. Candidate variants were identified by haplotype analysis (r2 ≥ 0.9, D'≥0.9) using 1000Genome LD data. To determine the effects of the variants on gene expression, expression quantitative trait loci (eQTL) were evaluated. To compare the expression of the identified genes in tumor samples, expression levels were compared between TCGA tumor types and adjacent normal tissues. Results: Six rs3820706, rs147451859, rs4784750, rs17587029, rs16830728, and rs16972207 variants were significantly associated with response to chemotherapy in BC patients (p < 5 × 10^-8). Seven novel haplotypic structures were identified to be associated with adverse response to chemotherapy in BC patients. These haplotypes formed two genetic structures associated with neutropenia, leukopenia, chemotherapy-induced cytotoxicity (GAG-TTAT), and chemotherapy-induced alopecia (CC-CAACTCCCGTTGCGG). These variants are located on PPCDC, NLRC5, STAM2, and TNFSF13B genes, and the expression of these genes significantly changed in BC tissues than normal tissues (P ≤ 0.05), also showing gene-gene correlation (P ≤ 0.05). Conclusions: These genetic variants and their associated novel haplotypic structures can predict adverse response to chemotherapy in BC patients and could potentially form BC-associated genetic panel for adverse response to chemotherapy.

Introduction: We compared the efficacy of first-generation granisetron and second-generation palonosetron in triplet anti-emetic prophylaxis in patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based high emetogenic chemotherapy (HEC).

Methods: This prospective, multicenter, non-randomized, observational study was conducted between June 2018 and December 2021. Patients diagnosed with NSCLC who received triplet anti-emetic prophylactic treatment with aprepitant and dexamethasone plus granisetron or palonosetron before the first cycle of chemotherapy were included in the study. At the end of the first week after chemotherapy, the emesis scale was applied to the patients during the outpatient control. The primary endpoint was complete response (CR) and total control (TC).

Results: One hundred twenty-one patients were included in the study. Sixty-one patients were in the granisetron group and 60 patients were in the palonosetron group. CR was higher with granisetron in the acute phase (70.5% vs. 58.3%, p = 0.16; respectively) and higher with palonosetron in the delayed phase (61.7% vs. 55.7%, p = 0.5; respectively), although not statistically significant. The TC rates were also not significantly different between the groups (54.1% vs.57.6%, p = 0.69).

Conclusions: There was no significant difference between granisetron and palonosetron in both acute and delayed control of emesis in NSCLC patients receiving cisplatin-based HEC.

Objective: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common subtype. Abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6, was approved to reduce risk of recurrence in high-risk, HR+, HER2-, early breast cancer based on the monarchE trial. The most common adverse events reported in monarchE were diarrhea, neutropenia, and fatigue. Real-world tolerability data and incidence of adverse events with abemaciclib in the adjuvant setting versus the metastatic setting is lacking.

Data sources: This is a retrospective analysis of HR+, HER2- breast cancer patients on abemaciclib from March 2018 to September 2021 at Robert H. Lurie Comprehensive Cancer Center in Chicago, Illinois. Incidence, grade of adverse events, dose reductions, and discontinuations were evaluated in patients taking abemaciclib in the adjuvant setting and the metastatic setting.

Data summary: Of the 30 patients included in this analysis, 100% experienced an adverse event of any grade. During treatment, 12.5% treated in the adjuvant setting and 35.7% in the metastatic setting experienced grade ≥3 adverse events. Adverse events leading to discontinuation of abemaciclib occurred in 18.8% of patients in the adjuvant setting and 57.1% in the metastatic setting.

Conclusions: This data suggests abemaciclib is better tolerated in high-risk, HR+, HER2-, node-positive, early breast cancer treated in the adjuvant setting compared to the metastatic setting. Management of adverse events is crucial to help patients stay on therapy to improve clinical outcomes. Real-world tolerability of abemaciclib in both the adjuvant and metastatic settings is of importance.

Objective: This article aims to expand on the existing literature regarding the incidence of withdrawal pain following discontinuation of Trk inhibitors and to explore strategies that mitigate this withdrawal pain.

Data source: A retrospective observational study was conducted among patients who were at least 18 years-old or older and had documentation of starting larotrectinib or entrectinib at University of California, San Francisco (UCSF) between November 2018 and November 2022. Data were collected from electronic records and pharmacy databases and a total of 21 patients were identified in this study.

Data summary: Of the 21 patients included in this study, five patients (24%) experienced pain during temporary or permanent discontinuation of Trk inhibitor with the onset of withdrawal pain ranging from a few hours to three days following discontinuation. Various strategies were implemented to manage this pain including restarting of Trk inhibitor, tapering of Trk inhibitor on discontinuation, minimizing dose interruptions and use of prescription pain medications.

Conclusion: This article illustrates the presence of withdrawal pain syndrome in patients stopping a Trk inhibitor treatment and highlight the need for patient education to avoid missing any doses and for development of a guideline for Trk inhibitor discontinuation.