Use Of Antineoplastic Agents Research Articles

Nuclear Receptors and Stress Response Pathways Associated with the Development of Oral Mucositis Induced by Antineoplastic Agents.

Oral mucositis (OM) is one of the common adverse events associated with cancer treatment that decreases the quality of life and affects treatment outcomes. However, the medications used to manage OM are generally only palliative, and our knowledge of the syndrome is limited. The etiology of the syndrome is thought to be complex and multifactorial. We investigated the trends and characteristics of OM and estimated molecular initiating events (MIEs) associated with the development of the syndrome using the FDA Adverse Event Reporting System. The study of trends and characteristics suggested that OM is significantly more likely to occur in females and nonelderly patients and is likely to be induced by protein kinase inhibitors such as afatinib and everolimus. Next, we used Toxicity Predictor, an in-house quantitative structure-activity relationship system, to estimate OM-associated MIEs. The results revealed that the agonist activity of the human pregnane X receptor, thyroid-stimulating hormone-releasing hormone receptor, and androgen receptor may be associated with OM development. Our study findings are expected to help avoid the risk of OM induction during the drug discovery process and clinical use of antineoplastic agents.

Linking physiology and demographics, non-ocular pathology and pharmaceutical drug use to standard OCT measures of the inner retina: The PPP project.

To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05). There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.

Assessing the risk of tumor lysis syndrome associated with the use of antineoplastic agents: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database.

The use of antineoplastic agents is one of the important triggers of tumor lysis syndrome (TLS), but there is still a lack of comprehensive understanding of antineoplastic agents that may trigger TLS and the TLS risk differences between different antineoplastic agents. This study aims to investigate the TLS risk of different antineoplastic agents and provide reference information for clinical practice. Real-world adverse events data in the FDA Adverse Event Reporting System (FAERS) database were used as the basis for the disproportionality analysis. We reviewed the TLS reports in the FAERS database from 2004 to 2022 to summarize an antineoplastic agent list that was reported to trigger TLS, based on which we conducted disproportionality analysis to assess the TLS risk of each antineoplastic agent. In all, 164 antineoplastic agents were reported to trigger TLS. On the whole, rituximab was the most reported antineoplastic agent in TLS reports, followed by cyclophosphamide, venetoclax, doxorubicin, and etoposide, while tagraxofusp was the antineoplastic agent with the highest adverse drug reaction (ADR) signal strength in signal detection, followed by floxuridine, pentostatin, tebentafusp, and venetoclax. Integrating ADR signal detection results, 129 of 164 antineoplastic agents showed at least one positive ADR signal, and six antineoplastic agents (bevacizumab, carboplatin, cisplatin, fluorouracil, lenvatinib, and paclitaxel) have the highest total number of positive signals. Further classifying the 164 antineoplastic agents into 46 chemical subgroups to conduct ADR signal detection, nitrogen mustard analogs were the most reported antineoplastic agent subclasses, followed by clusters of differentiation 20 inhibitors, and pyrimidine analogs, while clusters of differentiation 22 inhibitors were the antineoplastic agent subclass with the highest ADR signal strength, followed by podophyllotoxin derivatives and actinomycines. Our study showed the TLS risk characteristics of 164 antineoplastic agents by detecting and integrating ADR signals, which may help to optimize clinical practice.

First use of antineoplastic agents in women with breast cancer in the state of Rio de Janeiro, Brazil.

Context: Breast cancer is the most common cancer, except for non-melanoma skin cancer, among women in Brazil and worldwide. Breast cancer treatment involves surgery, radiotherapy and chemotherapy, which is used in 70% of patients. This study analyzes the utilization of antineoplastic agents among women undergoing their first round of chemotherapy in Brazil's public health system (SUS) in the state of Rio de Janeiro. Methods: Data from the SUS Outpatient Information System's authorizations for high-complexity outpatient procedures (APACs) billed between January 2013 and December 2019 were extracted, and three datasets were created: all type 1 and type 2 APACs (including all chemotherapy procedures performed); all type 1 APACs; and first type 1 APACs (containing data only for the first round of breast cancer chemotherapy). Names of antineoplastic agents were standardized to enable the subsequent classification of therapy regimens, mitigating limitations related to data quality. Absolute and relative frequencies were used to describe sociodemographic, clinical and treatment characteristics, therapy regimen and supportive drugs. Results: We analyzed 23,232 records of women undergoing their first round of chemotherapy. There was a progressive increase in the number of procedures over time. Women were predominantly white, lived in the capital and close to the treatment center. Most had stage 3 cancer at diagnosis (50.51%) and a significant proportion had regional lymph node invasion (37.9%). The most commonly used chemotherapy regimens were TAC (docetaxel, doxorubicine, cyclophosphamide) (21.05%) and and cyclophosphamide (17.71%), followed by tamoxifen (15.65%) and anastrozole (12.94%). Supportive drugs were prescribed to 386 women and zoledronic acid was predominant (59.58%). Conclusion: The findings point to important bottlenecks and possible inequities in access to treatment and medicine utilization for breast cancer patients in Brazil. Efforts to improve breast cancer treatment and prevention should not only focus on interventions at the individual level but address the disease as a public health problem. The study focused on women undergoing their first round of treatment, providing valuable insight into patient and treatment characteristics to inform policy decisions.

Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.

291 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19).Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications.Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates.Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.

Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.

e18693 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

Use of topical anti-inflammatory and antineoplastic agents in the treatment of young-aged actinic cheilitis: A systematic review.

Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC). A systematic review was conducted to analyze the potential of topical treatments for remission and clinical improvement of AC as well as patient acceptability. A systematic review of clinical trials was conducted following the PICO strategy to answer the following question: Are topical anti-inflammatory and antineoplastic agents effective in the treatment of actinic cheilitis? The quality of the studies was assessed by ROB-2, and the certainty of evidence was rated by GRADE guidelines. Eight clinical trials were selected, including four that investigated the use of anti-inflammatory drugs and four use of antineoplastic agents. The use of 3% diclofenac sodium was associated with partial remission of AC, while 5% imiquimod and ingenol mebutate promoted complete remission. Furthermore, 5% fluorouracil was the drug most associated with complications during treatment. Diclofenac sodium (3%) and fludroxycortide showed the best acceptance by the patients, especially in terms of symptom relief and comfort provided. The anti-inflammatory and antineoplastic agents analyzed largely provided good clinical outcomes, with evidence of remission of AC lesions, development of few local adverse reactions during treatment, and good patient adherence.

Two Targets, One Hit: new Anticancer Therapeutics to Prevent Tumorigenesis Without Cardiotoxicity.

A serious adverse effect of cancer therapies is cardiovascular toxicity, which significantly limits the widespread use of antineoplastic agents. The promising new field of cardio-oncology offers the identification of potent anti-cancer therapeutics that effectively inhibit cancer cell proliferation without causing cardiotoxicity. Future introduction of recently identified cardio-safe compounds into clinical practice (including ERK dimerization inhibitors or BAX allosteric inhibitors) is expected to help oncologists avoid unwanted cardiological complications associated with therapeutic interventions.

Survey on Off-Label Use of Antineoplastic Agents in Pediatric Patients using a Large-scale Medical Database in Japan

Survey on Off-Label Use of Antineoplastic Agents in Pediatric Patients using a Large-scale Medical Database in Japan

Prior History of Venous Thromboembolism Is a Significant Risk Factor for Recurrence of Thrombosis after Cancer Diagnosis

Introduction: The risk of venous thromboembolism (VTE) is increased in patients with cancer and contributes to significant morbidity, treatment delays and mortality. The Khorana score is the most well-validated VTE risk prediction tool that guides use of prophylactic anticoagulation in patients with cancer. The Khorana score includes cancer type, body mass index (BMI), hemoglobin, platelet count and leukocyte count but not a prior history of VTE which may increase the risk of recurrent VTE. Scant published data have suggested that a personal history of VTE increases the risk of VTE recurrence by 2 to 7-fold after cancer diagnosis. In this study, we examine the impact of history of VTE on VTE recurrence in a large cohort of patients with cancer. Methods: We performed a retrospective cohort study of patients diagnosed with cancer using aggregated de-identified data from electronic medical record of &amp;gt;300 major hospitals in US (IBM Watson Explorys). Patients with a personal history of VTE (deep vein thrombosis and/ or pulmonary embolism) more than one year prior to the diagnosis of cancer were included. Within this cohort, patients who developed recurrent VTE within 180 days of diagnosis of cancer were identified. The primary end-point was the incidence of cancer associated VTE (CVTE) in patients with prior history of VTE as compared to patients without history of VTE. Baseline characteristics including age, race, gender, BMI, prothrombotic mutations (Factor V Leiden, prothrombin gene 20210A mutation), antineoplastic agent use, cancer type and laboratory values (as included in Khorana risk score) were compared in all patients. Results: A total of 4,159,400 patients with a diagnosis of cancer were included. Of these, 138,820 patients (3.3%) had a history of VTE &amp;gt;1 year prior to being diagnosed with cancer. The incidence of CVTE at 180 days was 10-fold higher in those with prior history of VTE compared to those without (36.9% vs 3.66%; OR 15.4, 95% CI 15.22-15.6, P value &amp;lt;0.0001). While the inherent risk of CVTE varied based on cancer type (highest risk of 10.5% in pancreatic cancer), the risk of recurrent VTE in patients with prior VTE history is magnified to a similar degree across all cancer types as shown in Figure 1. Baseline characteristics including age, race, gender and cancer type distribution were similar in all groups, as shown in Table 1. Factor V Leiden mutation or activated protein C resistance (FVL/APC) was more prevalent in patients with prior history of VTE and subsequent CVTE (3%) as compared to all patients with CVTE regardless of history (1%), as shown in Table 1. A higher BMI was noted in patients with prior history of VTE (49% and 71% respectively in patients with and without CVTE) as compared to 41% in all patients with CVTE. Greater use of antineoplastic agents (41%) was noted in the group of patients with prior history of VTE and subsequent CVTE as compared to patients with prior VTE but no CVTE (36%). Conclusion: Our study highlights that a prior personal history of VTE &amp;gt;1 year before cancer diagnosis significantly increases the risk of cancer associated VTE independently, regardless of other established risk factors for VTE suggesting that this group of patients, especially those undergoing anti-cancer treatment may benefit from prophylactic anticoagulation. Increased incidence of FVL/ APC in patients with prior history of VTE and recurrent CVTE may reflect increased testing for prothrombotic mutations in this cohort. Our ongoing efforts include examining the effect of addition of history of VTE to the Khorana score. Finally, large prospective observational studies would be key to assess the impact of history of VTE on cancer thrombosis. Disclosures No relevant conflicts of interest to declare.

Development of the First Value Assessment Index System for Off-Label Use of Antineoplastic Agents in China: A Delphi Study.

ObjectiveTo develop the first value assessment index system for off-label use of antineoplastic agents in China.MethodsA modified two-round Delphi method was employed to establish consensus within a field to reach agreement via a questionnaire or doing interview among a multidisciplinary panel of experts by collecting their feedback to inform the next round, exchanging their individual knowledge, experience, and opinions anonymously, and resolving uncertainties.ResultsExpert’s positive coefficient was 94.74% in the first round and 100.00% in the second round. In the first round, expert’s authority coefficient for a majority of 61 indicators was ≥ 0.80 (85.2%, ranging from 0.70 to 0.89, mean=0.84) and coefficient of variation for all the 61 indicators was ≥ 22% (ranging from 11.67% to 21.74%, mean=17.4%). In two rounds, the mean expert’s authority coefficient raised to 0.85 (ranging from 0.75 to 0.90), and coefficient of variation for all indicators was < 20% (ranging from 10.49% to 19.71%, mean=15.97%). The P-values of Kendall’s W test were all < 0.001 for each round. At the end of two rounds, W-value for concordance was 0.395 (χ2=347.494, P<0.0001). The final value assessment index system comprised of eight domains, 21 subdomains, and 56 indicators. The weight and combination weight of each domain were 0.4211 for therapeutic value, 0.1678 for source and type of evidence, 0.0961 for public feedback/comments, 0.0894 for novelty in drug discovery, 0.0689 for grading of evidence recommendation, 0.0578 for consistency of evidence results, 0.0561 for disease burden, and 0.0428 for ratio of composition/integration.ConclusionUse of Delphi method to develop the proposed value assessment index system was found scientific and credible. This value assessment index system is highly appropriate for off-label use of antineoplastic agents in China.

Overall survival and second primary malignancies in men with metastatic prostate cancer.

BackgroundAmong prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC). We estimated overall survival and the incidence of SPM in men with mPC and mCRPC.MethodsIn the Prostate Cancer data Base Sweden, the National Prostate Cancer Register was linked to other national health care registers, 15,953 men with mPC in 1999–2011 were identified. Further, 693 men with mCRPC were identified. Outcomes were evaluated using stratified incidence rates, Kaplan-Meier estimators and Cox models.ResultsThe mean age among men with mPC was 73.9 years and in men with mCRPC 70.0 years. The median respective survivals were 1.5 (13,965 deaths) and 1.14 years (599 deaths), and average times since PC diagnosis 1.8 and 4.7 years. We observed 2,669 SPMs in men with mPC and 100 SPMs in men with mCRPC. The incidence rate of SPM per 1,000 person-years was 81.8 (78.8–85.0) for mPC and 115.6 (95.1–140.7) for mCRPC. High age, prior neoplasms, urinary tract infection, congestive heart failure, diabetes and renal disease were most strongly associated with increased mortality risk. Prior neoplasms and prior use of antineoplastic agents were most strongly associated with increased SPM risk. Several factors associated with increased mortality and SPM risks were more prevalent in the mCRPC cohort.ConclusionsOur results on mortality for men with mPC and mCRPC are in line with previous studies from the same time period. Investigation of factors associated with mortality and SPM in men with mPC and mCRPC can help to further understand these outcomes in the era prior to several new treatments have come available.

Abstract 3308: Impact of residency training programs on outcomes of tumor lysis syndrome: A study from national inpatient data

Abstract Background: Limited evidence is available on the effect of residency training on outcomes of tumor lysis syndrome (TLS) Objective: Our study measured the difference in outcomes in terms of inpatient length of stay (LOS), cost and mortality in patients with TLS between teaching and non-teaching hospitals. Design/Methods: We used the National Inpatient Sample (NIS) dataset, a national representative weighted sample of all US hospital discharges, from 2009 to 2014 to identify the diagnosis of TLS (ICD-9 code 277.88) in cancer patients. Data was matched and weighted for purpose of analysis. Hospitals were classified as teaching if they had one or more Accreditation Council for Graduate Medical Education (ACGME) approved residency programs, were a member of the Council of Teaching Hospitals (COTH) or had a ratio of full-time equivalent interns and residents to beds of .25 or higher. Categorical and continuous variables were tested using Chi-square test and Student t-test respectively. Multivariate hierarchical regression was used for the analysis of primary outcomes of interest. Results: We identified a total of 12,362 cases of TLS from 2009 to 2014. Among them, 6116 (49.47%) were admitted to non-teaching and 6246 (50.52%) to teaching hospitals. Both samples were identical in terms of baseline patient demographics. Patients in both samples were largely comparable in terms of comorbidities (non-teaching vs teaching): Obesity (10.2% vs 9.5%, p=0.166), liver failure (5.7% vs 5.1%,p=0.176), renal failure (20.2% vs 20.8%,p=0.406), coagulopathy (33.7% vs 33%,p=0.387) except for hypertension (46% vs 47.9%, p=0.04) which was more significant in the teaching hospital population. New onset renal failure requiring dialysis was found in 16.6% of the total population with equal distribution among both the samples (16.9% vs 16.3%, p=0.415). Seizures (1.7% vs 0.9%, p=&amp;lt;0.01) occurred more commonly in the non-teaching population while cardiac dysrhythmias (22.6% vs 27%, p&amp;lt;0.01) were significantly higher in the teaching population. Even though both the populations were comparable, the mean LOS (≈11.04 days vs ≈14.67, p &amp;lt;0.01) and cost (35,130.86$ vs 40,967.65$, p&amp;lt;0.01) were significantly higher at teaching hospitals with mean difference of 3.63 days and 15,168.47$ respectively. However, the mortality rate was higher in teaching hospitals (22.8% vs 24.7%,p= 0.014), but did not reach statistical significance on regression analysis (OR: 1.096, p=0.345) Conclusion: There is no overall mortality benefit for TLS patients treated at teaching hospitals despite having a significantly increased length of stay and cost. With poor overall outcomes for TLS patients and with increasing use of anti-neoplastic agents, early treatment and involvement of specialists is recommended. Further prospective trials are needed to determine an ideal cost effective strategy to address this oncologic emergency. Citation Format: Aakash Desai, Neel Patel, Hardik Sonani, Harsh Parmar, Aswanth Reddy. Impact of residency training programs on outcomes of tumor lysis syndrome: A study from national inpatient data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3308.

Antibiotic use and duration in association with Clostridioides difficile infection in a tertiary academic medical center: A retrospective case-control study

Previous literature has attributed the use of certain antibiotics to Clostridioides difficile infection (CDI); however, the time from administration to CDI onset is not adequately evaluated. We aimed to determine the type of antibiotics and duration of therapy associated with the highest CDI incidence at a tertiary academic medical center. This was a retrospective, case-control study of adult inpatients who received at least one course of antibiotic treatment. Patients were divided into either cases or controls. For cases, their first episode of CDI was a determining factor. Primary outcome were the types of antibiotics associated with risk of CDI development and the median time of antibiotic usage defining this risk. Of 601 patients who developed CDI, 313 were included as cases while 150 of 291 who received antibiotics but did not develop CDI were included as controls. Cefepime and cefazolin were significantly associated with increased risk for CDI with odds ratios of 3.01 (95% CI, 1.96–4.65; P < 0.001) and 1.71 (95% CI, 1.02–2.95; P < 0.05), respectively. Cefepime was associated with CDI after a median time of 8 days while CDI may have occurred after 6 days of therapy with cefazolin. Use of antineoplastic agents was significantly associated with CDI (odds ratio, 2.32; 95% CI, 1.35–4.13; P < 0.01). Antibiotic use increased the risk of CDI, particularly with cefepime and cefazolin with a median time to incidence of 8 and 6 days, respectively. CDI risk was also increased with the use of antineoplastic agents.

Extraction, isolation and in vitro evaluation of affinisine from Tabernaemontana catharinensis in human melanoma cells

Plant compounds have been identified as new drug prototypes. In this line, this work aimed to isolate the indole alkaloid affinisine from Tabernaemontana catharinensis and test its antitumor activity. The alkaloid was isolated by silica gel open column chromatography from the ethanolic extract of the stem of T. catharinensis. Afterwards, this molecule was characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In the next step, the cytotoxicity of the compound was tested against human melanoma cell lines (A375, WM1366 and SK-MEL-28) and a normal skin cell line (CCD-1059Sk) using a MTT (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cells treated with affinisine were evaluated by flow cytometry to analyze apoptosis and the induction of cell cycle arrest, to evaluate the dead mechanism. The metabolite was isolated in a 0.2% yield relative to the extract. Cytotoxic activity of the molecule was observed at 48 h, resulting in considerable growth inhibition rates in melanoma cells, especially in WM1366, which had the lowest IC50 (32.86 ± 2.54 µg/mL). The apoptosis rate was lower in A375 (56.66 and 86.71% with 57 and 65 µg/mL, respectively). Moreover, affinisine was able to significantly induce cell cycle arrest in different phases in the A375 and WM1366 cell lines. However, in SK-MEL-28 cells, cycle arrest was not observed. In summary, this compound significantly decreased the viability of tumor cells in a dose- and time-dependent manner for all evaluated lineages, reduced cell viability by the apoptosis mechanism and presented prominent activities of cell cycle arrest. In this way, the use of antineoplastic agents is among the most widely used therapeutic measures for the control and treatment of cancer. Affinisine is a promising prototype in the search for new drugs to treat cancer.

Nurses’ Compliance with Safety Guidelines for the Use of Antineoplastic Agents, Observable Symptoms, and Stress from Occupational Exposure

Purpose This study was done to identify the relationship between nurses’ compliance with safety guidelines for the use of antineoplastic agents, observable symptoms, and stress from occupational exposure. Methods The participants were 172 nurses from six general hospitals in a metropolitan area. They had administered antineoplastic agents at least three months prior to the study. Data were collected using self-report questionnaires, and then analyzed using SPSS/WIN 23.0 for descriptive statistics, t-test, one-way ANOVA, Scheffé method, and Pearson correlation coefficient. Results The average score on the guideline for safety compliance was 87.75 points out of a total of 100. The average score for observable symptoms of exposure to antineoplastic agents was 30.12 (28~56) points, and that for mean stress was 33.52 (15~60) points. Observable symptoms and stress from occupational exposure showed a statistically significant positive correlation (r=0.34, p<.001). Conclusion To increase the degree of compliance with safety guidelines for antineoplastic agents, hospitals should lower the chance of exposure to antineoplastic agents, as well as minimize the observable symptoms and stress from occupational exposure. Periodic education and policy support are needed to improve compliance with safety guidelines for antineoplastic agent use. 주요어: í•­ì•”ì œ, ì•ˆì „ê´€ë¦¬, 이행, 자각증상, ìŠ¤íŠ¸ë ˆìŠ¤ Key words: Antineoplastic agents, Safety, Compliance, Symptoms, Stress

Geographic Variations and Time Trends in Cancer Treatments in Taiwan

BackgroundTargeted therapies have become important treatment options for cancer care in many countries. This study aimed to examine recent trends in utilization of antineoplastic drugs, particularly the use of targeted therapies for treatment of cancer, by geographic region in Taiwan (northern, midwestern, southern, and eastern regions and the outer islands).MethodsThis was a retrospective observational study of antineoplastic agents using 2009-2012 quarterly claims data from Taiwan’s National Health Insurance Research Database. Yearly market shares by prescription volume and costs for targeted therapies among total antineoplastic agents by region were estimated. We used multivariate regression model and ANOVA to examine variations in utilization of targeted therapies between geographic regions and used ARIMA models to estimate longitudinal trends.ResultsPopulation-adjusted use and costs of antineoplastic drugs (including targeted therapies) were highest in the southern region of Taiwan and lowest in the outer islands. We found a 4-fold difference in use of antineoplastic drugs and a 49-fold difference in use of targeted therapies between regions if the outer islands were included. There were minimal differences in use of antineoplastic drugs between other regions with about a 2-fold difference in use of targeted therapies. Without considering the outer islands, the market share by prescription volume and costs of targeted therapies increased almost 2-fold (1.84-1.90) and 1.5-fold (1.26-1.61) respectively between 2009 and 2012. Furthermore, region was not significantly associated with use of antineoplastic agents or use of targeted therapies after adjusting for confounders. Region was associated with costs of antineoplastic agents but it was not associated with costs of targeted therapies after confounding adjustments.ConclusionsUse of antineoplastic drugs overall and use of targeted therapies for treatment of cancer varied somewhat between regions in Taiwan; use was notably low in the outer islands. Strategies might be needed to ensure access to cancer care in each region as economic burden of cancer care increase due to growing use of targeted therapies.

Protection behaviors for cytotoxic drugs in oncology nurses of chemotherapy centers in Shiraz hospitals, South of Iran.

Context:The use of antineoplastic agents for the treatment of cancer is an increasingly common practice in hospitals. As a result, workers involved with handling antineoplastic drugs may be accidentally exposed to these agents, placing them at potential risk for long-term adverse effects. This study aimed to determine the occupational protection status of clinical nursing staff exposed to cytotoxic drugs.Subjects and Methods:The study was designed as an analytic descriptive survey. The research settings took place in six centers of chemotherapy in Shiraz, Iran. The participants were 86 nurses who worked in oncology units and administered cytotoxic drugs. Data were collected using a questionnaire and a checklist which was developed by the investigators to determine occupational protection status of clinical nursing staff exposed to cytotoxic drugs. Percentage calculations and the independent samples t-test were used to see the general distribution and analysis of data. To statistically analyze of the data, SPSS software (version 16) was applied.Results:The mean age of participants was 30.52 ± 6.50 years and 66.27% of the nurses worked on inpatient oncology wards. The mean practice score was 21.1 ± 3.76 that ranged from 12.5 to 31. The independent samples t-test showed the outpatient nurses were weaker in practice (17.2 ± 2.52) in comparison with university hospitals (23.35 ± 3.02, P < 0.001). Occupational protection status of clinical nursing staff exposed to cytotoxic drugs especially during administration and disposal of medicines was poor and rarely trained with this subject and was observed under the standard conditions.Conclusions:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to cytotoxic drugs. It is recommended that all clinical nursing staff should receive full occupational protection training about these matters and the authorities provide standard conditions of oncology wards.

The Mechanistic Targets of Antifungal Agents: An Overview.

Pathogenic fungi are a major causative group for opportunistic infections (OIs). AIDS patients and other immunocompromised individuals are at risk for OIs, which if not treated appropriately, contribute to the mortality associated with their conditions. Several studies have indicated that the majority of HIV-positive patients contract fungal infections throughout the course of their disease. Similar observations have been made regarding the increased frequency of bone marrow and organ transplants, the use of antineoplastic agents, the excessive use of antibiotics, and the prolonged use of corticosteroids among others. In addition, several pathogenic fungi have developed resistance to current drugs. Together these have conspired to spur a need for developing new treatment options for OIs. To aid this effort, this article reviews the biological targets of current and emerging drugs and agents that act through these targets for the treatment of opportunistic fungal infections.