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American Journal of Therapeutics 2016The use of oral antineoplastic agents in nonmedical settings continues to increase. There are limited data available on pediatric exposures to these agents. We sought to... (Review)
Review
The use of oral antineoplastic agents in nonmedical settings continues to increase. There are limited data available on pediatric exposures to these agents. We sought to identify characteristics of such exposures. We performed a retrospective review of database of a statewide poison system from 2000 to 2009 for all cases of pediatric exposures to oral antineoplastic agents, which took place in a nonmedical setting. Data collected include gender, age, agent of exposure, dose, drug concentration, reason for exposure, symptoms, outcomes, interventions, and length of hospital stay. There were a total of 328 patients. The mean average age was 4.1 years. Eighty-nine percentage (n = 293) was unintentional. Exposures to 21 different antineoplastic agents were identified. Methotrexate (n = 91) and 6-mercaptopurine (n = 47) were the most common agents encountered. Two hundred ninety-nine (91%) cases had no symptoms reported. When reported, gastrointestinal symptoms (n = 17) and central nervous system sedation (n = 6) were most common. One case of pancytopenia was reported. No deaths were reported in this series. Sixty-seven percent (n = 220) were managed at home, whereas 19 (6%) were admitted to a health care facility. Cases were followed by the poison control center for 0.34 days (SD = 1.40). In this study, exposures to oral antineoplastics were primarily unintentional, asymptomatic, and managed at home. Study limitations include possible reporting bias, inability to objectively confirm exposures, and limited duration of monitoring by the poison control center. In this retrospective review, no significant morbidity or mortality was reported from pediatric exposures to oral antineoplastic drugs in the nonmedical setting.
Topics: Administration, Oral; Adolescent; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Poison Control Centers; Retrospective Studies
PubMed: 23884076
DOI: 10.1097/MJT.0b013e31829e8ba7 -
Farmacia Hospitalaria : Organo Oficial... Jun 2021To reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in order to facilitate the...
OBJECTIVE
To reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in order to facilitate the decision-making process in the event of extravasations.
METHOD
The panel of expert evaluators was made up of seven pharmacists belonging to the working group on extravasations. Other member served as coordinator. The likelihood of tissue damage was reviewed on the basis of eight reference documents. Four categories of drugs were established: vesicant (V); high risk irritant (HRI); low risk irritant (LRI) and non-irritant (NI). Two rounds of surveys were performed. The drugs with an agreement of less than 70% after the two rounds were discussed non-anonymously by the group. For each of the rounds the following was analysed: median of the degree of consensus and the interquartile range (IQR25-75), degree of agreement by tissue damage category, and percentage of antineoplastics reaching a degree of consensus of over 85% and of 100%. Drugs whose classification differed in the various reference documents were assessed separately. SPSS v23.0 statistical software was used.
RESULTS
Seventy-one antineoplastics were evaluated. In the first round, the median for degree of consensus was 100.0% (IQR25-75: 71.4- 100.0%). In the second round, the median was 100.0% (IQR25-75: 85.7- 100.0%). The percentage of antineoplastics with a consensus of 85.7% or above increased from 66.7% to 85.9% in the second round. For the 30 antineoplastics whose values differed in the reference documents, the degree of agreement increased from 71.4% (IQR25-75: 57.1-87.7%) to 100.0% (IQR25-75: 85.7-100.0%) in the second round. The percentage of antineoplastics with a consensus of 85.7% or above increased from 40.0% to 76.7%. Four antineoplastics had a degree of agreement of less than 70.0%. The final classification of drugs per category, was: 17 vesicants; 15 HRI; 13 LRI; and 26 NI. The final degree of consensus was 85.7% or above for 90.1% of antineoplastics, and 100.0% for 74.6% of the same.
CONCLUSIONS
In this area of scarce evidence and high variability, the Delphi method allows for consensus in classifying tissue damage risk, thus making it easier to reach clinical decisions. In approximately 90% of the antineoplastics, the degree of consensus reached by the expert panel was 85% or above. In 74% of the antineoplastics, it was 100%. This provides solid ground for management decisions.
Topics: Antineoplastic Agents; Consensus; Delphi Technique; Humans; Pharmaceutical Services; Pharmacy
PubMed: 34218766
DOI: 10.7399/fh.11625 -
Current Pharmaceutical Design 2009
Topics: Antineoplastic Agents; Drug Discovery
PubMed: 19275638
DOI: 10.2174/138161209787582200 -
European Journal of Medicinal Chemistry Dec 2022Cephalotaxine-type alkaloids (CTAs), represented by homoharringtonine (HHT, 1), display potent efficacy against different types of leukemia cells. In this study, a...
Cephalotaxine-type alkaloids (CTAs), represented by homoharringtonine (HHT, 1), display potent efficacy against different types of leukemia cells. In this study, a method for hydrogenation of β-substituted itaconic acid monoesters with chiral Ru[DTBM-SegPhos](OAc) was developed. This metal-catalyzed asymmetric hydrogenation enabled the convenient semisynthesis of novel cephalotaxine derivatives with chiral 2'-substituted-succinic acid 4-mono-methyl esters as side chains. The preliminary structure-activity relationship (SAR) of the compounds' antineoplastic activities was studied. Eventually, we discovered compound 10b with potent antineoplastic activities against leukemia and broadly anticancer activities against a panel of cancer cells. Our study provided a highly enantioselective process enabling the semisynthesis of cephalotaxine derivatives, which are interesting for further study on a scientific basis.
Topics: Humans; Homoharringtonine; Esters; Stereoisomerism; Harringtonines; Leukemia; Antineoplastic Agents
PubMed: 36242991
DOI: 10.1016/j.ejmech.2022.114731 -
Fortschritte Der Chemie Organischer... 1991
Review
Topics: Animals; Antineoplastic Agents; Bryostatins; Humans; Lactones; Macrolides; Molecular Conformation; Molecular Structure; Neoplasms
PubMed: 1937312
DOI: 10.1007/978-3-7091-9119-4_3 -
Profiles of Drug Substances,... 2016Dacarbazine is a cell cycle nonspecific antineoplastic alkylating agent used in the treatment of metastatic malignant melanoma. This chapter contains the descriptions of... (Review)
Review
Dacarbazine is a cell cycle nonspecific antineoplastic alkylating agent used in the treatment of metastatic malignant melanoma. This chapter contains the descriptions of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of dacarbazine and the methods that were used for its preparation are reported. The methods which were used for the physical characterization of the drug are ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The profile contains the spectra of the drug: ultraviolet spectrum, vibrational spectrum, nuclear magnetic resonance spectra, and mass spectrum. The compendial methods of analysis for dacarbazine include the United States Pharmacopeia methods, British Pharmacopeia methods, and International Pharmacopeia methods. Other reported methods that are used for the analysis of the drug are high-performance liquid chromatography, high-performance liquid chromatography-mass spectrometry, and polarography. Metabolism, pharmacokinetics, and stability studies on dacarbazine are also included. Reviews of some analytical methods and physicochemical properties of the drug as well as the most important enzymes that are involved in the prodrug activation are provided. Sixty-four references are listed at the end of this monograph.
Topics: Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Dacarbazine; Humans
PubMed: 26940170
DOI: 10.1016/bs.podrm.2015.12.002 -
Journal of Hematology & Oncology Jul 2023NEDDylation, a post-translational modification through three-step enzymatic cascades, plays crucial roles in the regulation of diverse biological processes.... (Review)
Review
NEDDylation, a post-translational modification through three-step enzymatic cascades, plays crucial roles in the regulation of diverse biological processes. NEDD8-activating enzyme (NAE) as the only activation enzyme in the NEDDylation modification has become an attractive target to develop anticancer drugs. To date, numerous inhibitors or agonists targeting NAE have been developed. Among them, covalent NAE inhibitors such as MLN4924 and TAS4464 currently entered into clinical trials for cancer therapy, particularly for hematological tumors. This review explains the relationships between NEDDylation and cancers, structural characteristics of NAE and multistep mechanisms of NEDD8 activation by NAE. In addition, the potential approaches to discover NAE inhibitors and detailed pharmacological mechanisms of NAE inhibitors in the clinical stage are explored in depth. Importantly, we reasonably investigate the challenges of NAE inhibitors for cancer therapy and possible development directions of NAE-targeting drugs in the future.
Topics: Humans; Ubiquitins; Neoplasms; Antineoplastic Agents; NEDD8 Protein
PubMed: 37525282
DOI: 10.1186/s13045-023-01485-7 -
Molecules (Basel, Switzerland) Nov 2021Continuous flow chemistry is by now an established and valued synthesis technology regularly exploited in academic and industrial laboratories to bring about the... (Review)
Review
Continuous flow chemistry is by now an established and valued synthesis technology regularly exploited in academic and industrial laboratories to bring about the improved preparation of a variety of molecular structures. Benefits such as better heat and mass transfer, improved process control and safety, a small equipment footprint, as well as the ability to integrate in-line analysis and purification tools into telescoped sequences are often cited when comparing flow to analogous batch processes. In this short review, the latest developments regarding the exploitation of continuous flow protocols towards the synthesis of anticancer drugs are evaluated. Our efforts focus predominately on the period of 2016-2021 and highlight key case studies where either the final active pharmaceutical ingredient (API) or its building blocks were produced continuously. It is hoped that this manuscript will serve as a useful synopsis showcasing the impact of continuous flow chemistry towards the generation of important anticancer drugs.
Topics: Antineoplastic Agents; Drug Screening Assays, Antitumor; Humans; Technology, Pharmaceutical
PubMed: 34834084
DOI: 10.3390/molecules26226992 -
Anais Brasileiros de Dermatologia 2022Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen.
BACKGROUND
Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen.
OBJECTIVE
To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment.
METHODS
A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital.
RESULTS
A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event.
STUDY LIMITATIONS
Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events.
CONCLUSION
A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.
Topics: Antineoplastic Agents; Hospitals; Humans; Neoplasms; Retrospective Studies; Skin
PubMed: 34844792
DOI: 10.1016/j.abd.2021.05.007 -
Mutation Research. Genetic Toxicology... Oct 2023Genotoxicity is an important information that should be included in human biomonitoring programmes. However, the usually applied cytogenetic assays are laborious and...
Genotoxicity is an important information that should be included in human biomonitoring programmes. However, the usually applied cytogenetic assays are laborious and time-consuming, reason why it is critical to develop rapid and economic new methods. The aim of this study was to evaluate if the molecular profile of frozen whole blood, acquired by Fourier Transform Infrared (FTIR) spectroscopy, allows to assess genotoxicity in occupational exposure to antineoplastic drugs, as obtained by the cytokinesis-block micronucleus assay. For that purpose, 92 samples of peripheral blood were studied: 46 samples from hospital professionals occupationally exposed to antineoplastic drugs and 46 samples from workers in academia without exposure (controls). It was first evaluated the metabolome from frozen whole blood by methanol precipitation of macromolecules as haemoglobin, followed by centrifugation. The metabolome molecular profile resulted in 3 ratios of spectral bands, significantly different between the exposed and non-exposed group (p < 0.01) and a spectral principal component-linear discriminant analysis (PCA-LDA) model enabling to predict genotoxicity from exposure with 73 % accuracy. After optimization of the dilution degree and solution used, it was possible to obtain a higher number of significant ratios of spectral bands, i.e., 10 ratios significantly different (p < 0.001), highlighting the high sensitivity and specificity of the method. Indeed, the PCA-LDA model, based on the molecular profile of whole blood, enabled to predict genotoxicity from the exposure with an accuracy, sensitivity, and specificity of 92 %, 93 % and 91 %, respectively. All these parameters were achieved based on 1 μL of frozen whole blood, in a high-throughput mode, i.e., based on the simultaneous analysis of 92 samples, in a simple and economic mode. In summary, it can be conclude that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.
Topics: Humans; Antineoplastic Agents; Occupational Exposure; Micronucleus Tests; Lymphocytes; DNA Damage
PubMed: 37770138
DOI: 10.1016/j.mrgentox.2023.503681