Administration Of Cytotoxic Drugs Research Articles

The Advent of Molecular Targeted Therapies Against Cancer. Toward Multi‐Targeting Drugs Through Materials Engineering: A Possible Future Scenario

The authors, actively engaged in the development of mesoporous silica‐based solutions, initially for modified drug release, later for the smart administration of conventional chemotherapeutic cytotoxic drugs, present the evolution of the concept of targeted therapy across different disciplines. They also discuss the diverse therapeutic needs and related challenges (adverse drug effects) that have unfolded over the last 30 years. Nanomedicine potentialities, mainly against cancers, that have emerged globally during the intense research activity of the last few decades, are critically discussed. The authors glimpse the growing potential of immune‐based therapeutic solutions, including those assisted by nanotechnology, as well as molecular targeted therapies (MTT) on which they focus. The advantages offered by targeted molecular therapies, despite the limits of monotargeted therapies, suggest the engineering of multi‐targeted therapies. Nanomedicine solutions such as ligand‐specific internalization and pH‐sensitive drug release that they have extensively tested and recently presented in open literature, still remain available instruments. According to the authors, MTT can offer shining perspectives in the near future that will depend on a thorough comprehension of nanostructures synthesis and tumor physiology. This article gives an interdisciplinary point of view tailored for non‐specialist readers imagining possible future scenarios in the field.

Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer.

Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI <25 kg/m2. This article is the first report in the literature on metronomic chemotherapy based on a topotecan + cyclophosphamide combination (CyTo). The CyTo regimen demonstrated safety, clinical activity, and potential broad clinical applicability in advanced OC patients and will be evaluated in a forthcoming clinical trial.

Electromotive Enhanced Drug Administration in Oncology: Principles, Evidence, Current and Emerging Applications.

Simple SummarySince the 17th century, the use of electric currents to improve the transport of drugs into human tissues has been described. Currently, electrically driven drug transport is used in a variety of medicinal fields such as the urinary system, skin, eye and others. In this review, we summarize the principles and factors that govern electrically driven drug transport and discuss its current and emerging applications for the treatment of cancer patients.Local-regional administration of cytotoxic drugs is an important adjunct to systemic chemotherapy amongst cancer patients. It allows for targeted delivery of agents at high concentration to target sites while minimizing systemic side effects. Despite the pharmacokinetic advantages of the local–regional approach, drug transport into tumor nodules remains limited due to the biophysical properties of these tissues. Electromotive enhanced drug administration (EMDA) represents a potential solution to overcome challenges in local drug transport by applying electric currents. Through electrokinetic phenomena of electromigration, electroosmosis and electroporation, electric currents have been shown to improve drug penetration and distribution in a wide variety of clinical applications. Amongst patients with non-muscular invasive bladder cancer (NMIBC) and basal and squamous cell skin cancers, EMDA has been successfully adopted and proven efficacious in several pre-clinical and clinical studies. Its application in ophthalmological and other conditions has also been explored. This review provides an overview of the underlying principles and factors that govern EMDA and discusses its application in cancer patients. We also discuss novel EMDA approaches in pre-clinical studies and explore future opportunities of developments in this field.

1526TiP TOLERANCE: An EORTC STBSG-QLG-ETF 3-arm randomized study on health-related quality of life of elderly patients with advanced soft tissue sarcoma undergoing doxorubicin alone three weekly or doxorubicin weekly or cyclophosphamide plus predniso(lo)ne treatment

Older patients with cancer require adequate treatment for which evidence-based data are still scarce. Prolongation of overall survival may not reflect the priority of older metastatic sarcoma patients who, more than younger patients, have a focus on Health-related Quality of life (HRQoL) . Doxorubicin has been the first line treatment for metastatic soft tissue sarcoma (mSTS) based on studies mainly carried out in patients under 65 years. Metronomic chemotherapy, defined as low-dose and frequent administration of cytotoxic drugs, is an alternative that can reduce acute toxicities and prevent tumour regrowth.

Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach.

BackgroundElectrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected.ConclusionsClinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life.

Calcium Electroporation Reduces Viability and Proliferation Capacity of Four Uveal Melanoma Cell Lines in 2D and 3D Cultures.

Simple SummaryCalcium electroporation (CaEP) is an innovative anti-tumor treatment modality that induces cell death by introducing supraphysiological concentrations of calcium into cells with a limited effect on normal cells. The objective of the present study is to assess the effect of CaEP in uveal melanoma (UM) cell lines in comparison to electrochemotherapy (ECT) with bleomycin using 2D monolayer cell cultures as well as 3D tumor spheroid models in four different UM cell lines. The morphological changes of the spheroids, the cell viability, growth rate as well as the cytotoxic effect of electroporation (EP) with calcium chloride and bleomycin were evaluated with various drug concentrations. The results of CaEP and ECT both suggest a comparable dose-dependent reduction in cell viability and proliferation rate in all tested 2D cell lines and 3D tumor spheroids. These data point out that CaEP is an established anticancer treatment causing cell death by ATP depletion in in vitro and in vivo, representing an efficient alternative therapy with a lower cytotoxic potency for the local UM tumor control.Electrochemotherapy (ECT) is the combination of transient pore formation following electric pulse application with the administration of cytotoxic drugs, which enhances the cytotoxic effect of the applied agent due to membrane changes and permeabilization. Although EP represents an established therapeutic option for solid malignancies, recent advances shift to the investigation of non-cytotoxic agents, such as calcium, which can also induce cell death. The present study aims to evaluate the cytotoxic effect, the morphological changes in tumor spheroids, the effect on the cell viability, and the cell-specific growth rate following calcium electroporation (CaEP) in uveal melanoma (UM) 2D monolayer cell cultures as well as in 3D tumor spheroid models. The experiments were conducted in four cell lines, UM92.1, Mel270, and two primary UM cell lines, UPMD2 and UPMM3 (UPM). The 2D and 3D UM cell cultures were electroporated with eight rectangular pulses (100 µs pulse duration, 5 Hz repetition frequency) of a 1000 V/cm pulse strength alone or in combination with 0.11 mg/mL, 0.28 mg/mL, 0.55 mg/mL or 1.11 mg/mL calcium chloride or 1.0 µg/mL or 2.5 µg/mL bleomycin. The application of calcium chloride alone induced an ATP reduction only in the UM92.1 2D cell cultures. Calcium alone had no significant effect on ATP levels in all four UM spheroids. A significant decrease in the intracellular adenosine triphosphate (ATP) level was documented in all four 2D and 3D cell cultures for both CaEP as well as ECT with bleomycin. The results suggest a dose-dependent ATP depletion with a wide range of sensitivity among the tested UM cell lines, control groups, and the applied settings in both 2D monolayer cell cultures and 3D tumor spheroid models. The colony formation capacity of the cell lines after two weeks reduced significantly after CaEP only with 0.5 mg/mL and 1.1 mg/mL, whereas the same effect could be achieved with both applied bleomycin concentrations, 1.0 µg/mL and 2.5 µg/mL, for the ECT group. The specific growth rate on day 7 following CaEP was significantly reduced in UM92.1 cell lines with 0.5 and 1.1 mg/mL calcium chloride, while Mel270 showed a similar effect only after administration of 1.1 mg/mL. UM92.1 and Mel270 spheroids exhibited lower adhesion and density after CaEP on day three in comparison to UPM spheroids showing detachment after day 7 following treatment. CaEP and bleomycin electroporation significantly reduce cell viability at similar applied voltage settings. CaEP may be a feasible and inexpensive therapeutic option for the local tumor control with fewer side effects, in comparison to other chemotherapeutic agents, for the treatment of uveal melanoma. The limited effect on normal cells and the surrounding tissue has already been investigated, but further research is necessary to clarify the effect on the surrounding tissue and to facilitate its application in a clinical setting for the eye.

Safe handling of cytotoxic drugs practices for nurses working with patients in middle euphrates oncology teaching hospitals

Background: The expanding use of chemotherapy medications has resulted in an increase in chemotherapeutics exposures amongst nurses who work in oncology departments. Chemotherapy drugs agents may have toxicological consequences in humans, such as carcinogenic effects, teratogenic effects, and mutagenicity (Sarita Devi, 2019). Objectives of the study: to assess nurses practices for safe preparation and administration of cytotoxic drugs in the oncology teaching hospitals. Methodology: descriptive–observational study design carried out to assess the nurses practices regarding safe of the preparation and administration of cytotoxic drugs .purposeful sample from (125) nurses who provide direct care for patient receiving chemotherapy drugs were selected. Result: Represent that most of the sample shows fair practice regarding preparation of chemotherapy (cytotoxic) that considered as key element of handling of cytotoxic medications in a safe manner, also that the majority of the nurses who participate in the study related to practical level of the study sample related to chemotherapy administration fair. Conclusion: Regarding the nurses practices with respect to the safe handling of cytotoxic drugs during their daily caring in the oncology units the statistical results recorded moderate level of practices.

Mucoadhesive Nanocarriers as a Promising Strategy to Enhance Intracellular Delivery against Oral Cavity Carcinoma.

Oral cancer, particularly squamous cell carcinoma (SCC), has posed a grave challenge to global health due to its high incidence, metastasis, and mortality rates. Despite numerous studies and favorable improvements in the therapeutic strategies over the past few decades, the prognosis of this disease remains dismal. Moreover, several drawbacks are associated with the conventional treatment; including permanent disfigurement and physical impairment that are attributed to surgical intervention, and systemic toxicity that results from aggressive radio- or chemotherapies, which impacts patients’ prognosis and post-treatment quality of life. The highly vascularized, non-keratinized oral mucosa appears as a potential route for cytotoxic drug administration in treating oral cancer. It acts as a non-invasive portal for drug entry targeting the local oral lesions of the early stages of cancer and the systemic metastasis sites of advanced cancer. The absorption of the poorly aqueous-soluble anti-cancer drugs can be enhanced due to the increased permeability of the ulcerous mucosa lining in the disease state and by bypassing the hepatic first-pass metabolism. However, some challenges in oral transmucosal drug delivery include the drugs’ taste, the limited surface area of the membrane lining the oral cavity, and flushing and enzymatic degradation by saliva. Therefore, mucoadhesive nanocarriers have emerged as promising platforms for controlled, targeted drug delivery in the oral cavity. The surface functionalization of nanocarriers with various moieties allows for drug targeting, bioavailability enhancement, and biodistribution at the site of action, while the mucoadhesive feature prolongs the drug’s residence time for preferential accumulation to optimize the therapeutic effect and reduce systemic toxicity. This review has been focused to highlight the potential of various nanocarriers (e.g., nanoparticles, nanoemulsions, nanocapsules, and liposomes) in conferring targeting, solubility and bioavailability enhancement of actives and mucoadhesive properties as novel tumor-targeted drug delivery approaches in oral cancer treatment.

Molecular tests for prediction of tumor sensitivity to cytotoxic drugs

Chemotherapy constitutes the backbone of cancer treatment. Several predictive assays assist personalized administration of cytotoxic drugs and are recommended for use in a clinical setting. The deficiency of DNA repair by homologous recombination (HRD), which is caused by inactivation of BRCA1/2 genes or other genetic events, is associated with high tumor responsiveness to platinum compounds, bifunctional alkylating agents and topoisomerase II poisons. Low activity of MGMT predicts the efficacy of nitrosoureas and tetrazines. Some clinically established pharmacogenetic tests allow for the adjustment of drug dosage, for example, the analysis of DPYD allelic variants for administration of fluoropyrimidines and UGT1A1 genotyping for the use of irinotecan. While there are promising molecular predictors of tumor sensitivity to pemetrexed, gemcitabine and taxanes, they remain in the investigational stage and require additional validation. Comprehensive molecular analysis of tumors obtained from drug responders and non-responders is likely to reveal new clinically useful predictive markers for cytotoxic therapy.

Silica-Based Stimuli-Responsive Systems for Antitumor Drug Delivery and Controlled Release.

The administration of cytotoxic drugs in classical chemotherapy is frequently limited by water solubility, low plasmatic stability, and a myriad of secondary effects associated with their diffusion to healthy tissue. In this sense, novel pharmaceutical forms able to deliver selectively these drugs to the malign cells, and imposing a space-time precise control of their discharge, are needed. In the last two decades, silica nanoparticles have been proposed as safe vehicles for antitumor molecules due to their stability in physiological medium, high surface area and easy functionalization, and good biocompatibility. In this review, we focus on silica-based nanomedicines provided with specific mechanisms for intracellular drug release. According to silica nature (amorphous, mesostructured, and hybrids) nanocarriers responding to a variety of stimuli endogenously (e.g., pH, redox potential, and enzyme activity) or exogenously (e.g., magnetic field, light, temperature, and ultrasound) are proposed. Furthermore, the incorporation of targeting molecules (e.g., monoclonal antibodies) that interact with specific cell membrane receptors allows a selective delivery to cancer cells to be carried out. Eventually, we present some remarks on the most important formulations in the pipeline for clinical approval, and we discuss the most difficult tasks to tackle in the near future, in order to extend the use of these nanomedicines to real patients.

Metronomic chemotherapy regimens and targeted therapies in non-Hodgkin lymphoma: The best of two worlds.

Novel drugs are rapidly moving forward the treatment-paradigm of non-Hodgkin-lymphomas (NHLs). Notwithstanding, especially in aggressive subtypes, chemotherapy remains the pillar of treatment. Indeed, the combination of highly effective Maximum-Tolerated-Dose Chemotherapy (MTD-CHEMO)+"novel drugs", has so far, fallen short from expectations, often because it caused excessive toxicity. Metronomic chemotherapy (mCHEMO), which is the frequent, long-term administration of low dose cytotoxic drugs, may allow more effective and tolerable combinations. mCHEMO pharmacodynamics, has been described as pleiotropic. In fact, it may have different cellular and molecular targets, when drugs or their schedules are modified. Although mCHEMO has been little explored in NHLs, pre-clinical studies - in lymphoma models - which addressed the activity of mCHEMO in combination with novel drugs, have shown very promising results. These included inhibitors of histone deacetylase, mTOR and PI3K/mTOR, as well as the immune checkpoint inhibitor anti-PD-L1. Moreover, a few impressive reports have recently shown all-oral mCHEMO schedules, with or without rituximab, can effectively shrink both B and T-cell aggressive NHLs. Indeed, these regimens allowed elderly-frail patients to achieve sustained remission, while toxicity proved manageable. In our opinion, all-oral mCHEMO, is an active, easy-to start, well-tolerated, and inexpensive therapeutic approach, which deserves further investigation. Most importantly, mCHEMO, holds promise to empower the activity of novel targeted therapies, without causing excessive toxicity.

Safety and effectiveness of gemcitabine for the treatment of classic Kaposi's sarcoma without visceral involvement.

Background:Classic Kaposi’s sarcoma (CKS) is a rare, multifocal, endothelial cell neoplasm that typically occurs in elderly people with previous infection by human herpes virus-8. Prospective trials are rare, and the choice of drugs relies on prospective trials performed on HIV-associated Kaposi’s sarcoma (KS). Pegylated liposomal anthracyclines and taxanes are considered the standard first- and second-line chemotherapy, respectively. Despite the indolent biologic behavior, the natural history is characterized by recurrent disease. This condition of chronic administration of cytotoxic drugs is often associated with immediate/long-term adverse events.Methods:This was an observational, retrospective study to evaluate the effectiveness and safety of gemcitabine in patients with CKS. From January 2016 to September 2021, the patients were treated with gemcitabine 1000 mg/m2 on days 1 and 8, with cycles repeated every 21 days. The treatment was administered as first or second line.Results:Twenty-seven (27) patients were included in the study. Twenty-one (21) out 27 patients (77.8%) achieved a partial response (PR), including 8 patients with major response (MR) (29.6%) and 13 patients with minor response (mR) (48.2%); 2 (7.4%) showed a complete response (CR), 3 (11.1%) a stable disease (SD), and 1 (3.7%) a progressive disease (PD). Tumor responses were generally rapid, with a median time to first response of 4 weeks (range, 3–12 weeks). Patients who responded had disease improvement with flattening of the skin lesions, decrease in the number of lesions, and substantial reduction in tumor-associated complications. Median duration of response was 19.2 months. Common adverse events were grades 1/2 thrombocytopenia, and grade 1 noninfectious fever. No patient discontinued treatment as a result of adverse events.Conclusion:Our study showed that gemcitabine is effective and well tolerated, acts rapidly on cutaneous lesions, and allows substantial symptom palliation, without dose-limiting toxicity. Gemcitabine represents a safe and effective option for the treatment of CKS.

Utility of indocyanine green in the administration of cytotoxic drugs in breast cancer patients

Indocyanine green has been widely introduced in breast cancer protocol for sentinel node detection, for upper limb lymphedema prevention and for breast reconstruction. However, more recent studies came to demonstrate that these particles can be also used in order to provide an efficient intraoperative detection of metastatic deposits as well as for a more targeted delivery of cytotoxic drugs. The current paper aims to investigate the mechanisms of action, the principles and the benefits of indocyanine green as a therapeutic tool, part of the medical oncologic treatment of breast cancer patients.

Comparison of safety and efficacy of fluorouracil + oxaliplatin + irinotecan (FOLFOXIRI) and modified FOLFOXIRI with bevacizumab for metastatic colorectal cancer: data from clinical practice.

The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. PFS was superior in group M (median PFS; 8.7 vs. 11.5months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6weeks/course, P = 0.051) in the induction term. We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

'KNOWLEDGE REGARDING SAFE HANDLING OF CYTOTOXIC DRUGS AMONG STAFF NURSES WORKING IN SELECTED HOSPITALS, KAMRUP (METRO), ASSAM, WITH A VIEW TO DEVELOP AN INFORMATION BOOKLET: A DESCRIPTIVE STUDY'.

National Institute for Occupational Safety and Health (NIOSH), 2019 stated that about 8 million healthcare workers are potentially exposed to hazardous drugs in their workplace. Indian Council of Medical Research (ICMR), 2019 reported around 16.9% of nurses had their skin or eyes exposed to chemotherapy drugs. Widespread use of cytotoxic drugs in the treatment of cancer has led to higher health hazards among nurses who handle and administer such drugs, so nurses should know how to protect themselves from the effects of cytotoxic drugs by following safety measures during preparation, administration of cytotoxic drugs, cytotoxic waste disposal, cytotoxic spills and rationale use of PPE (Personal Protective Equipment) like mask, cap, two pairs of gloves, gown and shoe cover. Aim: The aim of the study was to assess the knowledge regarding safe handling of cytotoxic drugs among staff nurses working in selected hospitals, Kamrup(Metro), Assam. Methods And Materials: A quantitative descriptive study was conducted on safe handling of cytotoxic drugs among staff nurses.100 staff nurses who were working in selected hospitals, Kamrup (Metro), Assam and who fullled the inclusion criteria have been selected by using convenience sampling technique. The conceptual framework used in the study was based on modied Ludwig Von Bertalanffy (1968) general system theory. The tools used for the study were structured knowledge questionnaire to assess the knowledge regarding safe handling of cytotoxic drugs. Results: Data analysis was done by calculating mean, SD and chi-square test. It was found that majority i.e.56% of the staff nurses had moderate knowledge, 38% had adequate knowledge and 6% had inadequate knowledge. There was signicant association of knowledge with selected demographic variables like working area, physical contact towards cytotoxic drugs exposure and training attended on safe handling of cytotoxic drugs. However, there was no signicant association of knowledge with other demographic variables i.e. age, educational qualication, specialized oncology training, total years of working experience and total years of experience in specic working area. Conclusion: Through this study, the investigator concluded that staff nurses are moderately aware regarding safe handling of cytotoxic drugs. It was expected that all the staff nurses should have adequate knowledge on safe handling of cytotoxic drugs. An information booklet was provided to the staff nurses of selected hospitals and vigorous training should also be provided to the staff nurses inorder to update their body of knowledge.

779P Metronomic low-dose capecitabine in metastatic, recurrent or persistent carcinoma of cervix as 3rd line and beyond

Systemic administration of cytotoxic drugs is the primary treatment strategy for patients with advanced carcinoma of cervix, but poor tolerance and side effects of the drugs led us to conduct this trial in patients who are ineligible for any type of intravenous chemotherapy.

Low Risk of Central Line-associated Bloodstream Infections in Pediatric Hematology/Oncology Patients.

Central venous lines (CVLs) are essential for standard care of pediatric hematology/oncology patients providing safe administration of cytotoxic drugs and pain-free blood sampling. Central line-associated bloodstream infections (CLABSIs) cause significant morbidity. This study describes the epidemiology, microbiology, and risk factors for CLABSI in all children with malignancies in Iceland. All children that were diagnosed with malignancy in Iceland and received a CVL during 2008-2017 were included in the study. Characteristics of CVLs and patients were registered, information on risk factors, and microbiology was collected. International standards were used for CLABSI definition. One hundred forty-three CVLs were placed in 94 children. Acute lymphoblastic leukemia was the most common underlying disease (31/94). Median age was 7 years. Implantable ports were the most commonly placed CVLs (82/143, 57%), tunneled lines were 39 (27%). Overall CLABSI rate was 0.24 infections/1000 line-days (14 episodes in 58,830 line-days), with little fluctuations. No CLABSI episodes occurred for 4 consecutive years (2012-2015). Staphylococci (of which 7 Staphylococcus aureus) were the cause of 10/14 episodes. Nine CLABSI episodes led to line removal, but no deaths were linked to CLABSIs. We report very low CLABSI rates over a 9-year period at our hospital, with 4 consecutive CLABSI-free years. Even with the addition of episodes of possible CLABSI, rates were still very low and lower than most published reports.

The effect of time ordering and concurrency in a mathematical model of chemoradiotherapy

We study the effect of switching the order of administration of cytotoxic drugs and radiation in cancer therapy by comparing a sequential and a concurrent protocol of chemoradiation. For this purpose, we derive a nonlinear ordinary differential equation model based on well-accepted knowledge of chemotherapy and radiotherapy for in vitro solid tumors. Using the bifurcation theory, we demonstrate that the administration of radiotherapy concurrently, once the chemotherapeutic regime has caused a considerable reduction of the tumor burden, might be more pertinent than the reverse strategy in those circumstances where bistability occurs. Consequently, our analysis suggests that an adequate time order and concurrency may have potential benefits in chemoradiation of solid tumors.

Sparse optimal control of a phase field system with singular potentials arising in the modeling of tumor growth

In this paper, we study an optimal control problem for a nonlinear system of reaction–diffusion equations that constitutes a simplified and relaxed version of a thermodynamically consistent phase field model for tumor growth originally introduced in H. Garcke, et al. [Math. Model. Methods Appl. Sci. 26 (2016) 1095–1148]. The model takes the effect of chemotaxis into account but neglects velocity contributions. The unknown quantities of the governing state equations are the chemical potential, the (normalized) tumor fraction, and the nutrient extra-cellular water concentration. The equation governing the evolution of the tumor fraction is dominated by the variational derivative of a double-well potential which may be of singular (e.g., logarithmic) type. In contrast to the recent paper [P. Colli, et al. To appear in: Appl. Math. Optim. (2019)] on the same system, we consider in this paper sparsity effects, which means that the cost functional contains a nondifferentiable (but convex) contribution like the L1−norm. For such problems, we derive first-order necessary optimality conditions and conditions for directional sparsity, both with respect to space and time, where the latter case is of particular interest for practical medical applications in which the control variables are given by the administration of cytotoxic drugs or by the supply of nutrients. In addition to these results, we prove that the corresponding control-to-state operator is twice continuously differentiable between suitable Banach spaces, using the implicit function theorem. This result, which complements and sharpens a differentiability result derived in [P. Colli, et al. To appear in: Appl. Math. Optim. (2019)], constitutes a prerequisite for a future derivation of second-order sufficient optimality conditions.

Survey of serious adverse events and safety evaluation of oral anticancer drug treatment in Japan: A retrospective study.

The present study assessed the safety of outpatient oral anticancer chemotherapeutic drugs by investigating the type and frequency of serious adverse effects (SAEs). Emergency hospitalization, unplanned consultations and telephone calls were investigated in 1,832 patients who received oral anticancer drug treatment at the National Cancer Center Hospital East between December 1, 2014 and November 30, 2015. Oral cytotoxic anticancer and molecular targeted drugs were administrated to 1,140 (62.2%) and 692 (37.8%) patients, respectively. A total of 52 (2.8%) SAEs were reported, with 32 (2.8%) occurring following cytotoxic anticancer drug administration and 20 (2.9%) occurring after molecular targeted drug treatment. The most common SAE was gastrointestinal toxicity. The median time to SAE occurrence was 32 days (range, 5-1,705 days). The rate of unplanned consultations and telephone calls were 5.5 and 37.9% among all patients, respectively, with skin reactions being the most common reason for unplanned consultations. SAEs often occurred early after treatment initiation. It was concluded that measures against gastrointestinal toxicity are particularly important were administering chemotherapeutic agents.