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Natural Product Research Aug 2022The study of medicinal plants for cancer treatment has gained attention due to an increasing incidence of cancer worldwide and antineoplastics-related undesirable... (Review)
Review
The study of medicinal plants for cancer treatment has gained attention due to an increasing incidence of cancer worldwide and antineoplastics-related undesirable secondary effects. Most of the natural products of medicinal plants that have been evaluated for cytotoxic activity, are derived from leaves, bark, roots and flowers. However, natural products derived from wood have demonstrated a cytotoxic effect with promising results. Moreover, some fractions and compounds have been isolated of wood in order to increase the effect. This review presents experimental evidence of cytotoxic effect of natural products from wood against cancer cell lines. It also provides considerations and recommendations to obtain herbal medicines over time.
Topics: Antineoplastic Agents; Cell Line, Tumor; Humans; Neoplasms; Plants, Medicinal; Wood
PubMed: 34459687
DOI: 10.1080/14786419.2021.1972420 -
Farmacia Hospitalaria : Organo Oficial... Dec 2021Indication of personalized pharmacotherapy in oncologic patients is based on the selection of the optimal treatment (drugs, dosing, routes and methods of... (Review)
Review
OBJECTIVE
Indication of personalized pharmacotherapy in oncologic patients is based on the selection of the optimal treatment (drugs, dosing, routes and methods of administration and duration) and on the most appropriate dosing method to achieve maximum antineoplastic efficacy, expressed in terms of remission or relapse-free time and acceptable toxicity for the patients. The aim of this study was to explore the contribution of therapeutic monitoring of plasma concentrations and of the application of the pharmacokinetic and pharmacodynamic information available for some widely used drugs to therapeutic personalization to the care of oncologic patients.
METHOD
A complete non-systematic literature review was carried out of the pharmacokinetic and pharmacodynamic properties of antineoplastic agents, as well as of the results of their use in clinical practice. The search for high quality articles included primary and secondary bibliographic sources. The benefits of therapeutic monitoring were evaluated for parenteral cytotoxic rugs, oral antineoplastic drugs, monoclonal antibodies and other biological therapies used in clinical practice.
RESULTS
Therapeutic personalization of antineoplastic drugs based on therapeutic monitoring of plasma concentrations together with the information provided by pharmacokinetic-pharmacodynamic models makes it possible to reduce toxicity and increase the effectiveness of treatment. When personalized treatment is established with high-dose methotrexate in patients with osteosarcoma, target maximum concentrations are reached in 70% of the cycles (49% when fixed doses are used). When 5-fluorouracil is used in patients with colorectal cancer, the response rate is 33.7% (18.3% with fixed doses). Similar benefit rates are obtained with asparaginase, busulfan, oral antineoplastics and monoclonal antibodies.
CONCLUSIONS
Due to the narrow therapeutic range of antineoplastic drugs and the highly variable clinical response they elicit, both in terms of effectiveness and safety, the monitoring of their plasma concentrations and the application of pharmacokinetic and pharmacodynamic principles and models constitute feasible and promising tools in the personalization of oncologic treatment.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Drug Monitoring; Humans; Medical Oncology; Neoplasm Recurrence, Local
PubMed: 35379110
DOI: No ID Found -
Handbook of Clinical Neurology 2012The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a... (Review)
Review
The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening.
Topics: Anticonvulsants; Antineoplastic Agents; Cerebellar Ataxia; Hazardous Substances; Humans; Neurotoxicity Syndromes; Neurotoxins
PubMed: 21827890
DOI: 10.1016/B978-0-444-51892-7.00012-7 -
Journal of Clinical Pharmacology Oct 2017Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size,... (Review)
Review
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese-even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area-guided dosing, therapeutic drug monitoring or pharmacokinetic-guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size-based dosing or "one dose fits all" is used. This review will focus predominantly on the rationale for pharmacokinetic-guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.
Topics: Administration, Oral; Antineoplastic Agents; Body Surface Area; Dose-Response Relationship, Drug; Drug Dosage Calculations; Humans; Molecular Targeted Therapy; Neoplasms; Obesity
PubMed: 28921641
DOI: 10.1002/jcph.937 -
BMJ Open Nov 2019In October 2012, the Chinese government established maximum retail prices for specific products, including 30 antineoplastic medications. Three years later, in June...
BACKGROUND
In October 2012, the Chinese government established maximum retail prices for specific products, including 30 antineoplastic medications. Three years later, in June 2015, the government abolished price regulation for most medications, including all antineoplastic medications. This study examined the impacts of regulation and subsequent deregulation of prices of antineoplastic medications in China.
METHODS
Using hospital procurement data and an interrupted time series with comparison series design, we examined the impacts of the policy changes on relative purchase prices (Laspeyres price index) and volumes of and spending on 52 antineoplastic medications in 699 hospitals. We identified three policy periods: prior to the initial price regulation (October 2011 to September 2012); during price regulation (October 2012 to June 2015); and after price deregulation (July 2015 to June 2016).
RESULTS
During government price regulation, compared with price-unregulated cancer medications (n=22, mostly newer targeted products), the relative price of price-regulated medications (n=30, mostly chemotherapeutic products) decreased significantly (β=-0.081, p<0.001). After the government price deregulation, no significant price change occurred. Neither government price regulation nor deregulation had a significant impact on average volumes of or average spending on all antineoplastic medications immediately after the policy changes or in the longer term (p>0.05).
CONCLUSION
Compared with unregulated antineoplastics, the prices of regulated antineoplastic medications decreased after setting price caps and did not increase after deregulation. To control the rapid growth of oncology medication expenditures, more effective measures than price regulation through price caps for traditional chemotherapy are needed.
Topics: Antineoplastic Agents; China; Drug Costs; Government Regulation; Interrupted Time Series Analysis
PubMed: 31784440
DOI: 10.1136/bmjopen-2019-031658 -
Journal of the National Comprehensive... Feb 2011
Topics: Antineoplastic Agents; Drug Discovery; Humans; Neoplasms; Patient Compliance
PubMed: 21357661
DOI: 10.6004/jnccn.2011.0126 -
Cancer Research Oct 2008Vitamin C is an antioxidant vitamin that has been hypothesized to antagonize the effects of reactive oxygen species-generating antineoplastic drugs. The therapeutic...
Vitamin C is an antioxidant vitamin that has been hypothesized to antagonize the effects of reactive oxygen species-generating antineoplastic drugs. The therapeutic efficacy of the widely used antineoplastic drugs doxorubicin, cisplatin, vincristine, methotrexate, and imatinib were compared in leukemia (K562) and lymphoma (RL) cell lines with and without pretreatment with dehydroascorbic acid, the commonly transported form of vitamin C. The effect of vitamin C on viability, clonogenicity, apoptosis, P-glycoprotein, reactive oxygen species (ROS), and mitochondrial membrane potential was determined. Pretreatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by trypan blue exclusion and colony formation after treatment with all antineoplastic agents tested. Vitamin C given before doxorubicin treatment led to a substantial reduction of therapeutic efficacy in mice with RL cell-derived xenogeneic tumors. Vitamin C treatment led to a dose-dependent decrease in apoptosis in cells treated with the antineoplastic agents that was not due to up-regulation of P-glycoprotein or vitamin C retention modulated by antineoplastics. Vitamin C had only modest effects on intracellular ROS and a more general cytoprotective profile than N-acetylcysteine, suggesting a mechanism of action that is not mediated by ROS. All antineoplastic agents tested caused mitochondrial membrane depolarization that was inhibited by vitamin C. These findings indicate that vitamin C given before mechanistically dissimilar antineoplastic agents antagonizes therapeutic efficacy in a model of human hematopoietic cancers by preserving mitochondrial membrane potential. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.
Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Cytoprotection; Dehydroascorbic Acid; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; K562 Cells; Mice; Mice, Inbred ICR; Mice, SCID; Neoplasms; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 18829561
DOI: 10.1158/0008-5472.CAN-08-1490 -
Bioorganicheskaia Khimiia Feb 1992The present review (for the previous part, see Bioorganicheskaya Khimia. 1990. V. 16. No 11. P. 1445-1464) describes the most important studies in the chemical... (Review)
Review
The present review (for the previous part, see Bioorganicheskaya Khimia. 1990. V. 16. No 11. P. 1445-1464) describes the most important studies in the chemical modifications of the sugar moiety of anthracycline antibiotics and their analogues during last ten years.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Carbohydrates
PubMed: 1605797
DOI: No ID Found -
Journal of Medicinal Chemistry Jan 2011
Review
Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Coordination Complexes; Humans; Neoplasms
PubMed: 21077686
DOI: 10.1021/jm100020w -
Clinical Chemistry Nov 1993Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic... (Review)
Review
Several anticancer drugs display characteristics that make them suitable candidates for therapeutic drug monitoring (TDM), including substantial pharmacokinetic variability and a narrow therapeutic index. However, concentration-effect relationships (pharmacodynamics) of most antineoplastic agents have not been well defined, thus limiting the widespread clinical application of TDM for cancer chemotherapy. Strategic incorporation of pharmacokinetic studies during phase I-III clinical trials should facilitate the identification of concentration-effect relationships and the definition of clinically useful levels of treatment intensity. We review representative clinical studies that have defined pharmacodynamic relationships for methotrexate, teniposide, etoposide, carboplatin, and mercaptopurine. Given that TDM has impacted positively on the clinical use of many drugs belonging to other therapeutic classes, and that pharmacodynamic correlations have been identified in several recent studies of anticancer drugs, we consider implementation of TDM a rational strategy for optimizing the use of selected antineoplastics.
Topics: Antineoplastic Agents; Drug Monitoring; Humans; Neoplasms
PubMed: 8222253
DOI: No ID Found