-
Environmental Toxicology and Chemistry May 2020Cancer is the second leading cause of death worldwide, with 9.6 million cancer-related deaths in 2018. Cancer incidence has increased over time, and so has the... (Review)
Review
Cancer is the second leading cause of death worldwide, with 9.6 million cancer-related deaths in 2018. Cancer incidence has increased over time, and so has the prescription rate of chemotherapeutic drugs. These pharmaceuticals, known as antineoplastic agents, enter the aquatic environment via human excretion and wastewater. The objectives of the present critical review were to investigate the risk of antineoplastics to aquatic species and to summarize the current state of knowledge regarding their levels in the environment, because many antineoplastics are not adequately removed during wastewater treatment. We conducted 2 separate literature reviews to synthesize data on the global environmental prevalence and toxicity of antineoplastics. The antineoplastics most frequently detected in the environment included cyclophosphamide, ifosfamide, tamoxifen, methotrexate, and 5-fluorouracil; all were detectable in multiple water sources, including effluent and surface waters. These antineoplastics span 3 different mechanistic classes, with cyclophosphamide and ifosfamide classified as alkylating agents, tamoxifen as a hormonal agent, and methotrexate and 5-fluorouracil as antimetabolites. Studies that characterize the risk of antineoplastics released into aquatic environments are scarce. We summarize the biological impacts of the most environmentally prevalent antineoplastics on aquatic organisms and propose an adverse outcome pathway for cyclophosphamide and ifosfamide, 2 widely prescribed drugs with a similar immunotoxic mode of action. Acute and chronic ecotoxicity studies using aquatic models are needed for risk characterization of antineoplastics. Environ Toxicol Chem 2020;39:967-985. © 2020 SETAC.
Topics: Antineoplastic Agents; Aquatic Organisms; Environmental Monitoring; Immunosuppression Therapy; Toxicity Tests; Water Pollutants, Chemical
PubMed: 32266737
DOI: 10.1002/etc.4687 -
Critical Care Nursing Quarterly Feb 1996Advances in the field of oncology have led to the development of many antineoplastic agents for the treatment of cancer. Combination with other agents and modalities,... (Review)
Review
Advances in the field of oncology have led to the development of many antineoplastic agents for the treatment of cancer. Combination with other agents and modalities, along with dose intensification, has resulted in more toxicities, often requiring careful management and monitoring in the critical care setting. Critical care nurses must meet this challenge by expanding their knowledge of antineoplastic therapy in order to skillfully care for these patients. The six major categories of antineoplastics, mechanism of action, indications for use, common route of administration, and major side effects are discussed.
Topics: Antineoplastic Agents; Critical Care; Drug Monitoring; Humans; Nursing Assessment
PubMed: 8689448
DOI: 10.1097/00002727-199602000-00002 -
Drug Safety Mar 1995With the use of numerous drugs in the treatment of cancer, the potential for drug interactions is considerable. Because of the limited therapeutic indices of anticancer... (Review)
Review
With the use of numerous drugs in the treatment of cancer, the potential for drug interactions is considerable. Because of the limited therapeutic indices of anticancer drugs, one should be aware that even small alterations in pharmacokinetics or pharmacodynamics may result in serious adverse effects. Pharmacokinetic drug interactions may alter absorption, bioavailability, distribution, metabolism and elimination patterns. For example, allopurinol inhibits the enzyme xanthine oxidase, thereby blocking the first-pass metabolism of mercaptopurine. Due to this drug interaction, plasma concentrations of mercaptopurine can increase up to 5-fold. Pharmacodynamic drug interactions are characterised by a similar or opposing pharmacological effect of both drugs upon the same biological system. For example, cotrimoxazole (trimethoprim-sulfamethoxazole) inhibits folic acid metabolism through direct binding to dihydrofolate reductase, an enzyme which is also inhibited by methotrexate. More pharmacological investigations are needed to understand the mechanisms and clinical implications of drug interactions with antineoplastic agents.
Topics: Antineoplastic Agents; Drug Interactions; Humans
PubMed: 7619329
DOI: 10.2165/00002018-199512030-00003 -
Journal of Oncology Pharmacy Practice :... Jul 2022Medication errors are avoidable occurrences that can assume clinically significant dimensions and impose relevant costs to the health system, especially in the context... (Review)
Review
BACKGROUND
Medication errors are avoidable occurrences that can assume clinically significant dimensions and impose relevant costs to the health system, especially in the context of antineoplastic therapy.
OBJECTIVE
Assess the clinical significance and economic impacts of a clinical pharmaceutical service. This retrospective study consists of an analysis of pharmacy interventions and drug-related problems found in a review of electronic prescriptions referring to antineoplastic therapy of a public teaching tertiary hospital in Brazil.
METHOD
Retrospective descriptive study obtained from electronic records of drug-related problems and pharmaceutical interventions related to antineoplastic therapy for oncological and hematological diseases, obtained through the pharmacotherapy review service. The accepted interventions were analyzed for the financial impact generated, evaluating your direct costs. The perception of clinical significance of a random sample of interventions was ascertained by the experts' opinion, using the Delphi method.
RESULTS
The most frequent problem was a "lack of information to professionals" (25.06%), "problems as to the frequency and interval of doses" (22.90%), and "medication underdosing" (16.20%). Dose adjustment (31.50%) and clarifications (30.90%) were the most frequent pharmaceutical interventions. In the second round of Delphi, experts rated 77.77% of interventions as extremely significant and very significant. The main drugs reported in the interventions were cyclophosphamide, carboplatin, methotrexate, folinic acid, and monoclonal antibodies. The savings amounted to US$1,193,970.18 and involved mainly bortezomib, dactinomycin, and monoclonal antibodies.
CONCLUSION
Clinical pharmacy services contributed to the rational use of medicines presenting clinical significance and avoiding waste of financial resources.
Topics: Humans; Retrospective Studies; Pharmacy Service, Hospital; Tertiary Care Centers; Brazil; Antineoplastic Agents; Pharmaceutical Preparations; Pharmacists
PubMed: 34000918
DOI: 10.1177/10781552211017650 -
Molecules (Basel, Switzerland) May 2022Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA... (Review)
Review
Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.
Topics: Antineoplastic Agents; Cell Line, Tumor; Water; Xanthones
PubMed: 35566290
DOI: 10.3390/molecules27092937 -
Oncology Nursing Forum Nov 2020Infusion of antineoplastic medications in nontraditional settings, including the home, is not a new concept. However, the emergence of the novel coronavirus, COVID-19,...
Infusion of antineoplastic medications in nontraditional settings, including the home, is not a new concept. However, the emergence of the novel coronavirus, COVID-19, has accelerated conversations around ensuring that patients with cancer can continue timely cancer treatment regimens while minimizing their risk of COVID-19 exposure and infection. Administration of antineoplastics through home infusion has been offered as a potential solution and continues to gain momentum among healthcare facilities and third-party payers.
Topics: Antineoplastic Agents; COVID-19; Coronavirus Infections; Home Infusion Therapy; Humans; Neoplasms; Oncology Nursing; Pandemics; Pneumonia, Viral; Risk; Societies, Nursing; United States
PubMed: 33063785
DOI: 10.1188/20.ONF.629-630 -
Therapeutic Drug Monitoring Feb 2020The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized... (Review)
Review
The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual patients often require dose modifications (amount or interval) or delays in dose administration as toxicities arise. In other areas of medicine, therapeutic drug monitoring is commonly and successfully used to ensure appropriate drug exposure and to limit dose-related toxicities. Currently, the wide pharmacokinetic variability of cytotoxic chemotherapies is addressed clinically by the use of body surface area to determine drug doses; however, this is outdated and demonstrably ineffective for this purpose. This review discusses the challenges of dosing cytotoxic chemotherapies, dose determination strategies for cytotoxic, targeted, and antibody-based biological anticancer drugs, and provides an overview of the recent literature regarding the use of therapeutic drug monitoring in cancer.
Topics: Antineoplastic Agents; Antineoplastic Agents, Immunological; Body Surface Area; Drug Dosage Calculations; Drug Monitoring; Humans; Neoplasms; Pharmacogenomic Variants
PubMed: 31568180
DOI: 10.1097/FTD.0000000000000701 -
Mutation Research. Reviews in Mutation... 2019Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated... (Meta-Analysis)
Meta-Analysis Review
Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated levels of chromosomal aberrations, micronuclei, and DNA damage have been documented in cancer patients. Elevations in these same biomarkers of genetic damage have been reported in numerous studies of healthcare workers, such as nurses and pharmacists, who routinely handle these drugs, but results vary across studies. To obtain an overall assessment of the exposure effect, we performed a meta-analysis on data obtained from peer-reviewed publications reporting chromosomal aberration levels in healthcare workers exposed to antineoplastic drugs. A literature search identified 39 studies reporting on occupational exposure to antineoplastic drugs and measurement of chromosomal aberrations in healthcare workers. After applying strict inclusion criteria for data quality and presentation, data from 17 studies included in 16 publications underwent meta-analysis using Hedges' bias-corrected g and a random-effects model. Results showed the level of chromosomal aberrations in healthcare workers exposed to antineoplastic drugs was significantly higher than in controls. The standardized mean differences (difference of means divided by within sd) from all studies were pooled, yielding a value 1.006 (unitless) with p<0.001. Thus, in addition to the documented genotoxic effects of antineoplastic drugs in cancer patients, this meta-analysis confirmed a significant association between occupational exposure to antineoplastics during the course of a normal work day and increases in chromosomal aberrations in healthcare workers. Based on the studies reviewed, we were unable to accurately assess whether appropriate use of protective measures might reduce the incidence of genetic damage in healthcare workers. However, given the potential for increased cancer risk linked to increases in chromosomal aberrations, the results of this study support the need to limit occupational exposure of healthcare workers to antineoplastic drugs as much as possible.
Topics: Animals; Antineoplastic Agents; Biomarkers; Chromosome Aberrations; DNA Damage; Health Personnel; Humans; Micronucleus Tests; Mutagens; Occupational Exposure
PubMed: 31416576
DOI: 10.1016/j.mrrev.2017.08.002 -
Critical Reviews in Oncology/hematology Apr 1994The use of antineoplastic agents in pregnant women poses obvious risks to both the patient and the developing fetus, particularly during organogenesis. While the use of... (Review)
Review
The use of antineoplastic agents in pregnant women poses obvious risks to both the patient and the developing fetus, particularly during organogenesis. While the use of antineoplastics during pregnancy is often unavoidable, the physician may limit the risks by having a clear knowledge of the pharmacology and teratogenic potential of individual agents. Specific physiologic changes in the pregnant patient, such as enhanced renal excretion of drugs, increased or decreased hepatic function, altered gastrointestinal absorption and enterohepatic circulation, altered plasma protein binding, an increase in plasma volume (50%), and creation of a fluid filled 3rd compartment (amniotic fluid) for water soluble drugs may all significantly influence the pharmacology of antineoplastic agents. These physiological changes may effect the pregnant patients ability to absorb orally administered drugs, metabolize drugs to either active or inactive metabolites, and eliminate cytotoxically active drugs. A resulting reduction in concentration x time (C x T) for drug exposure to the maternal system may reduce the efficacy of the antineoplastic agents, while an increase in C x T may expose the patient and her fetus to undue toxicity. The timing of drug administration to gestational age is also a critical factor for some drugs. While many drugs result in adverse effects on the fetus regardless of gestational age, others appear to pose less of a threat if administered beyond the first trimester. This review addresses the pharmacology, pharmacokinetics and the teratogenic potential of individual antineoplastic agents that are commonly used in pregnant patients. The aim of this review is to help the physician select, on a patient specific basis, antineoplastic agents that avoid at least some of the fetal risk involved while maintaining efficacy in the treatment of the patient.
Topics: Abnormalities, Radiation-Induced; Antineoplastic Agents; Busulfan; Cyclophosphamide; Cytarabine; Embryonic and Fetal Development; Female; Humans; Pregnancy; Pregnancy Complications, Neoplastic; Radiotherapy
PubMed: 8068213
DOI: 10.1016/1040-8428(94)90043-4 -
Expert Opinion on Investigational Drugs Dec 2000The influence of natural products upon anticancer drug discovery and design cannot be overestimated. Approximately 60% of all drugs now in clinical trials for the... (Review)
Review
The influence of natural products upon anticancer drug discovery and design cannot be overestimated. Approximately 60% of all drugs now in clinical trials for the multiplicity of cancers are either natural products, compounds derived from natural products, contain pharmacophores derived from active natural products or are 'old drugs in new clothes', where (modified) natural products are attached to targeting systems. This review covers those materials that the authors are aware of as being in clinical trials through early 2000 and demonstrates how, even today, in the presence of massive numbers of agents from combinatorial libraries, the compounds produced by 'Mother Nature' are still in the forefront of cancer chemotherapeutics as sources of active chemotypes.
Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Bacteria; Fungi; Humans; Marine Toxins
PubMed: 11093353
DOI: 10.1517/13543784.9.12.2783