Showing papers in "Journal of Oncology Pharmacy Practice in 2019"
TL;DR: Tocilizumab may be a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade, however, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.
Abstract: BackgroundImmune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs.MethodsThe character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over one hour. C-reactive protein was drawn at first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital discharge within seven days.ResultsOf the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were on c...
220 citations
TL;DR: The combination of pill count and patient self-report adherence is a way of improving oral antineoplastic adherence, however, significant barriers to adherence were identified such as forgetfulness, wanting to avoid side effects, feeling depressed or overwhelmed, and falling asleep before taking medications.
Abstract: PurposeThere is very little data on the effect of combining methods to better predict and improve oral antineoplastic adherence in cancer patients. The goal of this study was to evaluate the effect...
54 citations
TL;DR: Despite growing awareness and implementation of new safe handling guidelines, healthcare centers' surfaces remain contaminated with traces of many antineoplastic drugs, and the use of personal protective equipment remains indisputable.
Abstract: PurposeThe aim of this study was to monitor environmental contamination by 10 antineoplastic drugs in Canadian oncology pharmacy and patient care areas. The secondary objective was to explore the i...
35 citations
TL;DR: The value of the oncology pharmacist was demonstrated by published articles in four key themes: clinical care, patient education, informatics, and cost savings.
Abstract: IntroductionAlthough many oncology pharmacists are embedded members within the healthcare team, data documenting their contributions to optimal patient outcomes are growing. The purpose of this pap...
34 citations
TL;DR: A case of a female patient with glioblastoma multiforme, who was treated with the programmed cell death-1 receptor inhibitor nivolumab and subsequently developed aplastic anemia is presented.
Abstract: Directed immunotherapy at the programmed cell death-1 receptor has demonstrated efficacy in non-small-cell lung cancer, metastatic melanoma, and various other malignancies. Immune checkpoint inhibitors are innovative therapies producing some impressive clinical responses with a more manageable adverse effect profile when compared to traditional chemotherapy. The more common adverse effects associated with these agents include fatigue, rash, myalgia, pyrexia, and cough, but less common yet serious adverse effects have included immune-mediated colitis, pneumonitis, hepatitis, type 1 diabetes, and encephalitis. Here we present a case of a female patient with glioblastoma multiforme, who was treated with the programmed cell death-1 receptor inhibitor nivolumab and subsequently developed aplastic anemia.
33 citations
TL;DR: Clinical pharmacy services may have optimized therapy effectiveness, prevent adverse effects and unclear/compliant problems, and indicate the presence of a great convenience and need to implement Clinical pharmacy services in alternative hospitals in Northern Cyprus.
Abstract: BackgroundClinical pharmacists have important roles in implementing scientifically valid knowledge and advice on safe, reasonable use of pharmaceuticals Clinical pharmacy services were introduced
32 citations
TL;DR: Utilization of steroids for immune-related adverse effect at this institution is highly variable, with the majority of patients received prolonged courses of steroids and resumed checkpoint inhibitor therapy with concomitant steroids above recommended doses.
Abstract: IntroductionDue to enhanced T-cell activity, immune checkpoint inhibitors cause immune-related adverse effects. Corticosteroids are the mainstay of immune-related adverse effect management but the ...
31 citations
TL;DR: All four cyclin-dependent kinase 4/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma.
Abstract: Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor to gain Food and Drug Administration (FDA) approval, specifically as monotherapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy and endocrine therapy. Abemaciclib also shares a similar indication with palbociclib for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Trilaciclib use remains largely investigational at this time. However, despite FDA-approval for only metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, all four cyclin-dependent kinase 4/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors. Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma. We discuss the approved indications, current research, and areas of future exploration for palbociclib, ribociclib, abemaciclib, and trilaciclib.
28 citations
TL;DR: A patient who developed SJS after 16 weeks of therapy with nivolumab is presented, a week prior to this event, he developed a pruriginous papulo-erythematous rash.
Abstract: Nivolumab is a fully human immunoglobulin G4 immune checkpoint inhibitor antibody approved for use in the treatment of several malignancies. Severe side effects such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have only extremely rarely been reported with this drug. We present herein a patient who developed SJS after 16 weeks of therapy with nivolumab. A week prior to this event, he developed a pruriginous papulo-erythematous rash. Prompt recognition of this phenomenon, immune checkpoint inhibitor discontinuation and steroid therapy are necessary steps in order to avoid dismal outcomes.
26 citations
TL;DR: The available data on updates in the treatment of UC is reviewed and future direction of therapies are reviewed, including dose-dense gemcitabine and cisplatin for muscle-invasive bladder cancer and preoperative checkpoint blockade.
Abstract: Urothelial Carcinoma (UC) is the second most common malignancy of the genitourinary system and is the sixth most common cancer in the USA. Over a decade prior to 2016, the standard of care for early disease consisted of transuretheral resection of the bladder tumor with or without intravesicular chemotherapy or immunotherapy. Systemic chemotherapies such as gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin were reserved for recurrent, muscle-invasive, advanced or metastatic disease. Novel treatment approaches for UC have significantly impacted the management of patients. In 2016-2017, five immune checkpoint inhibitors marked a new paradigm in the treatment of UC for patients with advanced or metastatic disease or who are unable to tolerate platinum-based chemotherapy. Most recently, the U.S. Food and Drug Administration set restrictions on two commonly utilized checkpoint inhibitors, atezolizumab and pembrolizumab, in the first-line setting in patients with UC due to decreased survival associated with low expression of the protein programmed death ligand 1. Furthermore, Breakthrough Therapy Designations have been granted for enfortumab vedotin and erdafitinib for patients following platinum-based chemotherapy and those with fibroblast growth factor receptor mutated UC, respectively. Additional updates include dose-dense gemcitabine and cisplatin for muscle-invasive bladder cancer and preoperative checkpoint blockade. This article will review the available data on updates in the treatment of UC and future direction of therapies.
25 citations
TL;DR: The role of clinical pharmacist in an oncology setting of Nepal is highlighted to work as a bridge between medical oncologist and patients.
Abstract: The clinical pharmacist's part is emerging as a key extension to the human services care team bringing about enhanced patient care in the world. The main objective of this article is to highlight the role of clinical pharmacist in an oncology setting of Nepal. An enrollment of clinical pharmacist in an oncology hospital or in oncology settings can work as a bridge between medical oncologist and patients.
TL;DR: A case of Stevens-Johnson syndrome occurring in a patient who had previously tolerated pembrolizumab without significant side effects for seven months is presented.
Abstract: Pembrolizumab is a humanized antibody that targets programmed cell death receptor-1. This agent is approved for use in the treatment of several malignancies. While pruritus and papulo-erythematous rash are not uncommon with its use, severe reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis are very rare. We present herein a case of Stevens-Johnson syndrome occurring in a patient who had previously tolerated pembrolizumab without significant side effects for seven months. Prompt recognition of Stevens-Johnson syndrome/toxic epidermal necrolysis and discontinuation of the offending agent are paramount to ensure a favorable outcome.
TL;DR: Investigating whether cancer patients receiving anti-PD-1/ PD-L1 therapy, while taking PPIs concurrently, will have a different outcome compared to those who are not using PPIs found that PPI use was associated with a decreased diversity of the gut microbiome as compared to the non-users.
Abstract: Cancer immunotherapy is one of the most rapidly evolving fields in medicine. Immune checkpoint inhibitors act by releasing a molecular brake-like programmed death-1 (PD-1) or its ligand PD-L1, thus enabling the immune system to attack and destroy cancer cells. These drugs are used to treat a number of patients with a wide variety of solid tumors including metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial cancer, head and neck cancer, gastroesophageal cancer, hepatocellular carcinoma, and hematologic malignancies like Hodgkin’s lymphoma. Currently, there are several Food and Drug Administration-approved immune checkpoint inhibitors that target the PD-1/PD-L1 pathway: nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. A healthy immune system is capable of destroying tumor cells. However, tumor cells and antigen-presenting cells often express immune checkpoints like PD-L1 on their surface. When PD-L1 molecules bind to PD-1 molecules on T cells, they inhibit T-cell function and the tumor cells evade immune surveillance. Immune checkpoint inhibitors directed against PD-1/PD-L1 restore immune function by inhibiting those inhibitory molecules. Unbalancing of immune system leads to immunerelated adverse events (IRAEs) in some patients treated with anti-PD-1/PD-L1 therapy. Diarrhea/colitis and pneumonitis are frequent causes of hospitalization among patients receiving immunotherapy. Grade 3/4 immune-mediated diarrhea/colitis are seen in approximately 1 to 2% of cases, while the incidence of grade 3/4 pneumonitis have been reported in up to 1% patients. Other IRAEs include endocrinopathies, hepatotoxicity, renal toxicity, and dermatologic toxicity. Recently, the composition of gut microbiome has been an active area of interest in cancer immunotherapy. Gopalakrishnan et al. analyzed the oral and fecal microbiome in melanoma patients treated with anti-PD-1/PD-L1 therapy and showed that there is a significant difference in the diversity and composition of gut microbiome among responders vs. nonresponders. In their study, they showed that the within sample diversity of gut microbiome, which takes into account both the number of different species as well as their relative distribution, was significantly higher among responders compared to non-responders. Proton pump inhibitors (PPIs) are commonly used around the world for different indications including gastro-esophageal reflux disease and prevention and treatment of peptic ulcer disease. In 2013, esomeprazole (PPI), was the second largest drug in the US in terms of revenue. A recent study by Imhann et al. found that PPI use was associated with a decreased diversity of the gut microbiome as compared to the non-users. Based on the information presented above, it was hypothesized that cancer patients receiving anti-PD-1/ PD-L1 therapy, while taking PPIs concurrently, will have a different outcome compared to those who are not using PPIs. A retrospective review was performed on 158 patients aged 18 years or older, treated at the University of Oklahoma Health Sciences Center with anti-PD-1/PD-L1 therapy between 2014 and 2016. PPI use was assessed based on medical record review of prescribed and self-reported medications. This study was approved by the institutional review board. Our primary objective was to investigate whether the
TL;DR: A case of autoimmune myocarditis leading to biventricular failure after four doses of IV ipilimumab 3 mg/kg as a single agent is presented, suggesting this toxic effect may be anticipated with PD1 inhibitors.
Abstract: An important agent in melanoma therapy, ipilimumab is associated with autoimmune toxicity. Two cases of autoimmune pericarditis and large pericardial effusion have been documented with its use. Rep...
TL;DR: The approaches taken to assure safe handling of hazardous drugs varied considerably in some cases, and the content and scope of safe handling guidelines and pharmacy practices among the participating countries revealed considerable variation.
Abstract: PurposeA survey of guidelines and current practices was conducted to examine the safe handling procedures for antineoplastic and other hazardous drugs that are used in 24 countries including the Am...
TL;DR: Prophylactic granulocyte colony-stimulating factor use was appropriately highest for high-risk regimens and lowest for low- Risk regimens yet still potentially underused in high risk regimens, overused in low-riskRegimens, and not appropriately targeted in intermediate-risk Regimens, indicating a need for further education on febrile neutropenia risk evaluation and appropriate granulocytes colony- stimulation factor use.
Abstract: ObjectiveInappropriate granulocyte colony-stimulating factor use with myelosuppressive chemotherapy has been reported Using the Oncology Services Comprehensive Electronic Records electronic medica
TL;DR: This review aims to analyse and discuss the results of each degradation or decontamination procedure and to compare them, to facilitate selection of the method to be implemented in daily practice.
Abstract: Although considerable efforts have been made over the last 40 years, occupational exposure to antineoplastic drugs is still a daily concern, since eradicating such contamination from workplaces seems unattainable. Considerable data are currently available on the risks associated with their use at work. Hospital facilities are often cleaned with marketed antimicrobials whose chemical decontamination efficacy certainly differs but remains unknown. To keep compounding facilities sterile, alcohol-based solutions are frequently used but with very limited efficiency. It would be particularly useful if a decontamination method could be added to the means already available so that all conventional antineoplastic drug contamination could be removed. Several degradation methods or desorption methods have previously been experimented, with varying success. They have never been compared or discussed in terms either of efficiency or usability. This review aims to analyse and discuss the results of each degradation or decontamination procedure and to compare them. This should facilitate selection of the method to be implemented in daily practice.
TL;DR: Counselling by an oncology pharmacist was effective in decreasing patient concerns and increasing their understanding of the necessity of the medication, thus enhancing their adherence and consequently improving the care they received.
Abstract: BackgroundMultiple factors have been reported to affect adherence to medication, including beliefs about medicines, while specifically tailored pharmaceutical care services for patients may improve...
TL;DR: The objective of this article is to provide an overview of the target patient population, the neurotoxic effects of WBRT, current treatment options, and a summary of the available literature surrounding the use of memantine in this setting.
Abstract: Whole brain radiotherapy is the mainstay of treatment for patients suffering from stage IV malignancies that have metastasized to the brain. Although this therapy is often effective at reducing tumor size and burden, it is associated with a spectrum of toxicities that often result in irreversible cognitive decline. Various drug and non-drug therapies have been evaluated to treat this neurotoxicity after whole brain radiotherapy is administered; however, currently available options have shown little benefit or come with side effects themselves that may outweigh the benefits of their use. For this reason, current investigations are focusing on preventing cognitive decline, rather than attempting to attenuate symptoms after they occur. Memantine has consistently shown promise in both in-vitro and in-vivo studies as a neuroprotective agent that may improve cognitive outcomes in patients undergoing whole brain radiotherapy. Memantine use prior to and during whole brain radiotherapy has been shown to significantly delay time to cognitive failure and reduce the rate of decline in memory, cognitive function, and processing speed. Its use has also been linked to significant decreases in brain edema, brain infarct size, and brain vasculature changes following whole brain radiotherapy. Memantine offers a promising safety profile with high tolerability and limited side effects. The objective of this article is to provide an overview of the target patient population, the neurotoxic effects of WBRT, current treatment options, and a summary of the available literature surrounding the use of memantine in this setting.
TL;DR: Two patients who experienced anthracycline-induced cardiomyopathy and were successfully managed with sacubitril/valsartan after suboptimal responses to traditional evidence-based heart failure therapies are reported.
Abstract: BackgroundSacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in adult patients with reduced ejection fraction when compar...
TL;DR: Physicochemical and biological analyses demonstrate that Rixathon®/Riximyo® stability is not impacted by dilution and formulation conditions required for intravenous infusion, even under worst case conditions with regard to product shelf life, temperature excursion, light exposure, dilution factor and infusion bag storage time over a 31-day period.
Abstract: PurposeThe purpose of this study was to evaluate the in-use physicochemical and biological stability of the Sandoz rituximab biosimilar, marketed under the trade names Rixathon® and Riximyo® in the European Union, upon preparation for intravenous infusion.MethodsThree batches of Rixathon®/Riximyo® in the final month of their 36 month shelf life were exposed to room temperature and light for 14 days to recapitulate a major temperature excursion. Samples were diluted to the lowest allowable concentration of 1 mg/mL in 0.9% NaCl solution in either polypropylene or polyethylene infusion bags and stored for 14 or 30 days at 5 ± 3℃ followed by an additional 24 h at room temperature to simulate product handling. Samples stored in infusion bags were analyzed using SEC, CEX, non-reducing CE-SDS, peptide mapping and CDC to assess physicochemical and biological stability.ResultsAnalysis of Rixathon®/Riximyo® diluted to the lowest allowable concentration in 0.9% sodium chloride in either polypropylene or polyethylene...
TL;DR: A clinical pharmacist was integrated into a Precision Medicine Program for oncology patients using somatic testing to identify actionable mutations and apply targeted therapy to malignancies and was readily accepted as an addition to the team by both oncologists and patients and the experience served as an important learning opportunity.
Abstract: PurposeThe implementation, benefits, and challenges of clinical pharmacist services within a Precision Medicine Program for cancer patients are described. By relating the practice model that was de...
TL;DR: It is prudent for practitioners to recognize early vision abnormalities in patients receiving PD-1 antagonists to prevent permanent vision loss, as two patients who developed vision loss while on pembrolizumab treatment are reported.
Abstract: BackgroundVision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembroli...
TL;DR: Although the results support outpatient pharmacy cancer services, significant heterogeneity and bias in the study designs prohibit robust conclusions and further controlled trials are required.
Abstract: BackgroundPatients receiving anticancer therapies are frequently prescribed complex and high-risk medication regimens, which at times can result in medication misadventures. The objective of this r...
TL;DR: In heavily pretreated patients with refractory/relapsed solid tumors, the vincristine, irinotecan, and temozolomide regimen seemed promising in Ewing sarcoma patients and was well tolerated.
Abstract: BackgroundAlthough the survival of pediatric cancer has increased dramatically in the last decades, the survival of refractory, relapsed, and metastatic cases is still dismal. The combination of ir...
TL;DR: Data from this study have highlighted avenues for pharmacists to make an impact on patients newly started on oral chemotherapy, and opportunities exist to increase patient education, ensure appropriate follow-up, and assess adherence while preventing and managing treatment-related toxicities.
Abstract: PurposeAlthough oral chemotherapy offers advantages over intravenous chemotherapy, it creates a unique set of challenges Potential barriers include treatment complexity, patient responsibility for
TL;DR: It is concluded that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.
Abstract: Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness. Patient 1 was worked up for health care-associated pneumonia, as well as acute sinusitis prior to the diagnosis of cryptococcal meningoencephalitis. He also had a more complex past medical history than patient 2. Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. Cryptococcal antigen testing was done sooner in this patient due to patient receiving high-dose steroids for the treatment of underlying hemolytic anemia. We conclude that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.
TL;DR: Based on the results of this study, only two out of the six closed system transfer device brands passed testing criteria for both tasks, functioning as truly closed systems.
Abstract: PurposeThe National Institute for Occupational Safety and Health (NIOSH) released a proposed protocol in 2015 to evaluate the vapor containment abilities of closed system transfer device technologies in order to provide meaningful comparisons between products. This study assessed the vapor containment ability of closed system transfer devices when following the methodology as outlined by the 2015 NIOSH proposed protocol.MethodsThis study evaluated six closed system transfer device brands following the draft NIOSH vapor containment protocol. The testing evaluated each closed system transfer device brand during both compounding (Task 1) and administration (Task 2). Five pre-specified steps for each task were repeated for a total of four manipulations per device. The Thermo Scientific™ MIRAN SapphIRe XL Infrared Analyzer was used to detect isopropyl alcohol vapor levels after each step.ResultsFor Task 1, two closed system transfer device products (PhaSeal™ and Equashield®) adequately contained the isopropyl ...
TL;DR: This is the first study to clarify the benefits of outpatient pharmacy services in which pharmacists collaborate with oncologists at an outpatient clinic for the management of adverse drug reactions in cancer patients in Japan.
Abstract: BackgroundCollaboration between pharmacists, doctors, and nurses in outpatient treatment is beneficial; however, such services are limited in Japan due to the lack of a healthcare reimbursement fee...
TL;DR: Midostaurin represents the first FDA-approved treatment targeted against FLT3, and there are several promising agents currently undergoing clinical trials that show activity in the presence of these mutations.
Abstract: FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is responsible for the proliferation and survival of hematopoietic stem cells in acute myeloid leukemia. Although patients with FLT3 mutations have similar rates of remission following induction chemotherapy, relapse rates are significantly higher and patients with FLT3 mutations have significantly worse outcomes for overall survival and disease-free survival. Early FLT3 inhibitors, such as sorafenib, were non-selective and inhibited several tyrosine kinase receptors resulting in significant toxicity. The treatment of FLT3-positive acute myeloid leukemia has advanced recently with the development of a several FLT3-targeting agents that are either approved or in development. Midostaurin represents the first FDA-approved treatment targeted against FLT3, and there are several promising agents currently undergoing clinical trials. Although certain mutations confer resistance to earlier generation FLT3-targeted tyrosine kinase inhibitors, newer agents show activity in the presence of these mutations.