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OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.
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In recent years, the rapid increase in cancer treatment costs in China had brought a huge economic burden to society, and it was urgent to standardize the rational application of anti-tumor drugs. In the context of the reform of group payment related to disease diagnosis, a tertiary first-class hospital focused on the needs of patients and guided by value-based healthcare, established a professional and normalized refined anti-tumor drug management system, setted up a multidisciplinary diagnosis and treatment team, and promoted " Internet plus pharmaceutical services" in December 2018.From 2019 to 2021, the proportion of hospital drugs were 30.8%, 30.1%, and 27.3%, respectively. The amount of money spent on anti-tumor drugs were 83.25 million yuan, 76.41 million yuan, and 62.48 million yuan, respectively, showing a decreasing trend year by year. The practice of refined management of anti-tumor drugs fully reflected the core concept of value based healthcare, achieving closed-loop management of the entire process of drugs, improving the level of rational drug use, reducing the economic burden on patients, and providing reference for improving the level of rational use of anti-tumor drugs in public hospitals.
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Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.
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OBJECTIVE To provide the suggestions and reference for the follow-up update of Guiding Principles of Clinical Application of Novel Anti -tumor Drugs （hereinafter referred to as “Guiding Principles ”）. METHODS The update of 2018-2021 editions of Guiding Principles were compared ；the changes of its style ，the variety and quantity of novel anti-tumor drugs ，the classification of indications ，the target ，the inclusion of medical insurance and other aspects were analyzed. Its change trend and possible problems were summarized. RESULTS There was a great change in the style of Guiding Principles in 2020 edition，i.e. deleting the item of “clinical application management ”and adding the item of “attached table ”. Totally 33 novel anti-tumor drugs were included in the 2018 edition of Guiding Principles ，and the number of novel anti-tumor varieties increased to 46，60 and 77 in 2019，2020 and 2021 editions，respectively. The time when the new varieties were included in Guiding Principles was the same year or one year after the domestic market time. Totally 26 varieties of national medical insurance negotiation were included in the 2018 edition of Guiding Principles ，and 8，10 and 12 varieties were added respectively in 2019，2020 and 2021 editions on the basis of the previous edition . Novel anti-tumor drug in the 2018 edition of Guiding Principles mainly focused on traditional targets such as EGFR，HRE2 and VEGFR. However ，since 2019，the number of new targets such as PD-1，PARP，ALK and CDK had been increasing，among which domestic original drugs accounted for a large proportion. CONCLUSIONS The revision of Guiding Principles aims to further guide the clinical application of novel anti-tumor drugs from the professional level of health technology. The new varieties and indications conform to the principles of scientificity and dynamics ；domestic original varieties have developed rapidly ，and innovative varieties to novel target have emerged. The follow-up update of Guiding Principles should refer to authoritative medical guidelines and high-quality evidence- based evidence. Attention should be paid to the types of tumors lacking therapeutic drugs and the clinical value of oushun- novel anti-tumor drugs.
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OBJECTIVE：To study the abnormal use of anti-tumor dr ugs i n the clinic in order to provide reference for rational use of drugs in the clinic. METHODS ：Referring to foreign and domestic anti-tumor drug use guidelines and literatures ，Guidelines for Clinical Use of New Anti-tumor Drugs （2018 edition），Off-label Drug Use List （2019 edition），Practical Oncology （secondary edition），anti-tumor drug package inserts approved by FDA and package inserts of anti-tumor drug listed in China ，abnormal use of antitumor drugs （including instructions ，special indications ，and the order of administration of new anti-tumor drugs ） was summarized and analyzed. RESULTS & CONCLUSIONS ：The off-label use of anti-tumor drugs were summarized in this paper ， including 11 drug varieties and 4 kinds of off-label drug items ，such as off-label drug use plan （recombinant human endostatin ， rituximab），off-label administration route （pemetrexed disodium ，bortezomib，bevacizumab），off-label administration lines （erlotinib，gefitinib），off-label drug dosage （actinomycin D ，gemcitabine，ifosfamide，etoposide）. They should be carefully selected and strictly monitored in clinical use ，and treatment plan should be adjusted according to needs. Among the special indications，cyclophosphamide，cytarabine，methotrexate and cisplatin were used in large doses ，which were 2 000-2 400 mg/m2， 2 000 mg/m2，12 g/m2 and 80-120 mg/m2，respectively；individual differences should be paid attention to and therapeutic drug monitoring should be carried out if necessary. In the scheme of combination of new anti-tumor drugs or traditional chemotherapy drugs，there were 5 categories and 11 items in total ，such as combination of molecular targeted anti-tumor drugs with traditional chemotherapy drugs （such as docetaxel at first ，gefitinib at the same time or later ），combination of target immunocheckpoint drugs with traditional chemotherapy drugs （such as platinum at first ，then nivolumab ），and molecular targeted anti-tumor drugs combination（such as pertuzumab and trastuzumab should be given in sequence ，in either order ）. In clinical use ，histopathological diagnosis should be made clear ， and drugs with specific targets should be used after gene detection and strictly follow the indications.
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Exosomes are naturally nanometer-sized (40-100 nm) vesicles that contribute to the communication among the cells through the proteins, lipids and RNA which they carried. Exosomes derived at different physiological conditions play different role, which therefore can be widely used in the diagnosis and treatment of cancer. Besides, exosomes as the natural nanomaterials have the unique advantage in drug delivery system. Although the intrinsic advantages of exosomes have evoked a surge of interest, improvements in standardized isolation techniques with high efficiency and robust yield are still a huge challenge. Here, we provide an overview of the isolation and the application of exosomes in drug delivery system.
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Cytotoxic anti-tumor drugs are characterized by narrow therapeutic indexes, severe toxicity and great difference in the effects of individualized therapies, while studies of pharmacogenomics (PGx) can provide biomarkers for predicting the efficacy and toxicity of chemotherapy drugs. PGx biomarkers play an important role in predicting the safety, toxicity and effects of drugs in the treatment of tumors. By identifying specific polymorphisms of PGx biomarkers, physicians could select and customize medication regimens based on the patient's genetic profile. This review focuses on the germline PGx biomarkers that are currently used for guiding therapeutic decisions and have potential clinical application values, including thiopurine S-methyltransferase and thiopurine, NUDT15 and thiopurine, UGT1A1 and irinotecan, DPYD and fluorouracil, CYP2D6 and tamoxifen, and TPMP and cisplatin.
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Cancer therapeutics-related cardiac dysfunction(CTRCD)is receiving more attention.Risk factors assessment before cancer therapy,cardiac function monitoring during and after cancer therapy,and early detection and treatment of myocardial injury are key to preventing clinical heart failure.The incidence and severity of cardiotoxicity can be reduced by measures such as reducing drug dose,adjusting administration route,and using low toxic drugs.Cardioprotective agents including anti-heart failure drugs and dexrazoxane are important for the prevention and treatment of CTRCD.Patients with advanced heart failure may also benefit from mechanical treatments including cardiac resynchronization therapy and mechanically-assisted ventricular devices.This article reviews the recent advances in the prevention and treatment of CTRCD.
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Humans , Cardiotoxicity , Heart , Heart DiseasesABSTRACT
OBJECTIVE:To shorten the turnover days of hospital drug inventory,reduce the cost of drug inventory and improve the level of hospital drug inventory management.METHODS:The data of 65 kinds of antitumor drugs and its adjuvant drugs during Jan.1st,2016-Dec.31st,2016 were collected from hospital information system (HIS) of our hospital,such as price,inventory to classify by using ABC classification method.According to demanded quantity of class A drugs in the secondary drug storage,the amount purchased of upper and lower limitation of class A drugs could be calculated.The data of class C drugs were analyzed one by one to determine the "temporary use" drug directory.The turnover days of class A drugs and the inventory cost of class C drugs were counted before and after classification management.RESULTS:There were 10 class A drugs,accounting for 15.38％ of total types and 78.27％ of total consumption sum;the turnover days of pharmacy inventory decreased from (43.96 ± 19.04) d to (13.64 ± 8.02) d by adopting the principle of purchasing in small quantity by several times.There were 10 "temporary use" drugs of class C drugs,accounting for 26.32％ of total types,270 thousand yuan inventory cost saved each year.CONCLUSIONS:Hierarchical management of hospital drug inventory by ABC classification can effectively optimize the inventory types and amount,and provide definite evidence for "temporary use" drugs so as to shorten turnover days of pharmacy inventory and recue the cost of pharmacy inventory.
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OBJECTIVE:To construct evaluation system for rational use of anti-tumor drugs and evaluate the effects. METH-ODS:Based on medical records of 1 927 malignant tumor patients in our hospital during Jan.-Oct. 2014,the study adopted Delphi method to determine the evaluation indexes. Referring to foreign and domestic authoritative guidelines,related literatures and drug package inserts,according to evidence-based pharmacy method,the evaluation system for rational use of anti-tumor drugs in our hospital was established from 6 aspects such as chemotherapy plan,drug dose,drug pretreatment,solvent selection,drug concen-tration,dosing frequency. The tumor patients receiving chemotherapy were selected from our hospital in May(pre-intervention group,98 cases)and Dec.(post-intervention group,87 cases)in 2015,the special comment was conducted by using above sys-tem. The utilization of anti-tumor drugs was compared between 2 groups before and after intervention. RESULTS:The unreason-able utilization rate of anti-tumor drugs was 62.2% in pre-intervention group and 29.9% in post-intervention group;the unreason-able rates of drug dose,drug pretreatment,drug concentration and chemotherapy plan decreased from 30.6%,21.4%,8.2%, 6.1% to 12.6%,6.9%,4.6%,2.3%,respectively,with statistical significance(P<0.05). Irrational solvent selection and dosing frequency had not been improved significantly,without statistical significance(P>0.05). CONCLUSIONS:The establishment of evaluation system for rational use of anti-tumor drugs can improve irrational use of anti-tumor drugs. It is certainly feasible and can provide reference for clinical pharmacists standardizing clinical use of anti-tumor drugs.
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OBJECTIVE:To construct evaluation system for rational use of anti-tumor drugs and evaluate the effects. METH-ODS:Based on medical records of 1 927 malignant tumor patients in our hospital during Jan.-Oct. 2014,the study adopted Delphi method to determine the evaluation indexes. Referring to foreign and domestic authoritative guidelines,related literatures and drug package inserts,according to evidence-based pharmacy method,the evaluation system for rational use of anti-tumor drugs in our hospital was established from 6 aspects such as chemotherapy plan,drug dose,drug pretreatment,solvent selection,drug concen-tration,dosing frequency. The tumor patients receiving chemotherapy were selected from our hospital in May(pre-intervention group,98 cases)and Dec.(post-intervention group,87 cases)in 2015,the special comment was conducted by using above sys-tem. The utilization of anti-tumor drugs was compared between 2 groups before and after intervention. RESULTS:The unreason-able utilization rate of anti-tumor drugs was 62.2% in pre-intervention group and 29.9% in post-intervention group;the unreason-able rates of drug dose,drug pretreatment,drug concentration and chemotherapy plan decreased from 30.6%,21.4%,8.2%, 6.1% to 12.6%,6.9%,4.6%,2.3%,respectively,with statistical significance(P<0.05). Irrational solvent selection and dosing frequency had not been improved significantly,without statistical significance(P>0.05). CONCLUSIONS:The establishment of evaluation system for rational use of anti-tumor drugs can improve irrational use of anti-tumor drugs. It is certainly feasible and can provide reference for clinical pharmacists standardizing clinical use of anti-tumor drugs.
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OBJECTIVE:To provide the new idea for clinical pharmacists providing pharmaceutical care in oncology depart-ment. METHODS:Applying the principles and methods of clinical pathway,the pharmaceutical care of anti-tumor drugs could be divided into before medication,during medication,after medication and patient education,according to the sequence of taking med-icine. On the basis of evidence-based medicine,the care contents of each unit were established,and the pharmaceutical care path-way (PCP) was formed. During chemotherapy duration for a breast cancer metastasis patient with liver function injury,clinical pharmacists conducted pharmaceutical care for drug pretreatment,ADR monitoring and disposal,patient education,as well as put forward the proposal of drug treatment as supplementing calcium,adjusting the dose of epirubicin and paclitaxel targeting on PCP of zoledronic acid,epirubicin and paclitaxel. RESULTS:Physicians adopted the pharmacist’s recommendations. The patient suf-fered from joint and muscle pain during chemotherapy,and the symptom was relieved after symptomatic treatment by celecoxib;chest and back discomfort was relieved significantly after chemotherapy,and the disease condition kept stable. The patient was dis-charged from the hospital. CONCLUSIONS:PCP focus on the time,content and countermeasures of pharmaceutical care,the pro-gram and treatment results of pharmaceutical care,and promote standardization,formalization,simplification and procedure of pharmaceutical care. Clinical pharmacists conduct individualized pharmaceutical care rapidly targeting on PCP so as to deepen the communication of clinical pharmacists with physicians,nurses and patients,and promote the development of pharmaceutical care smoothly.
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@#Thioredoxin reductase(TrxR)is a seleniferous homodimeric flavoenzyme, which is ubiquitously expressed in all cells and plays a crucial role in the redox regulation of numerous celluar signaling pathways involved in cell survival and proliferation. TrxR maintains cellular redox equilibrium. Recent researches have illuminated that TrxR overexpressed in many tumors, is closely associated with the evolution, progression and apoptosis of tumor. TrxR contains a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. The TrxR inhibitors as novel target-drug in cancer therapy have been extensively studied and elucidated. This article summarized the latest progress in TrxR inhibitors according to the binding capacity of TrxR and substrate.
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OBJECTIVE:To explore the method for the scientific and standard management of clinical trial drugs. METHODS:By theory analysis and empirical analysis,the management model of clinical trial drugs in our hospital was introduced in terms of software and hardware construction of clinical trial pharmacy,the formulation of drug management system and standard operation procedure,regular quality control and drug information management platform construction,etc. RESULTS:In the experience of our hospital,it could safeguard the safety of drug use in subjects and scientificity and preciseness of drug clinical trial results through the concentrated administration trial drugs by full-time pharmacists according to national laws and regulations,management system and standard operation procedure,and regular quality control inspection by quality control group. CONCLUSIONS:Drug clinical trial institute strictly abide the requirements of Good Clinical Practice,strengthen the management of trial drugs and im-prove information management continuously,which is of important significance to construct standardized,detailed and high-effi-ciency centralized management system of clinical trial drugs.
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Objective: To design and synthesize conjugates of polyglutamic acid and gemcitabine with different amino acids as linkers, and through changing the structure to control the release of free drug and improve antitumor activity. Methods: First, the amino acid esters formed with 3′-OH or 5′-OH of gemcitabine were synthesized, and then the free amino groups of amino acid esters were conjugated with the carboxyl groups in polyglutamic acid to obtain the object conjugate of polyglutamic acid and gemcitabine with different amino acids as linkers. The content of gemcitabine in the conjugates was determined by UV. The release rate of free drug from the conjugates was determined by HPLC. Results and Conclusion: 11 novel conjugates were synthesized with gemcitabine content of 25%-30%. In vitro drug release experiment results revealed that gemcitabine could be released from the conjugates steadily. Conjugates with different amino acids as linkers exhibited different drug release rate. PG-Ala-3′-Gem can release 50% of gemcitabine in 4 h, but PG-Val-3′-Gem and PG-Ala-5′-Gem only can release 30.3% or 43.5% of gemcitabine in 48 h,respectively. The drug release rate in blood is faster than that in water solution.
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Telomerase can inhibit the shortening of telomere and stimulate continuous cell proliferation to form tumor.The activity of telomerase can be prohibited by G-quadruplex formed by the single chain in G-rich field of telomere 3' end, resulting in tumor cell apoptosis.Ligands which can induce the formation or stabilize the structure of G-quadruplex in G-rich field of oncogene exhibit antitumor function. Nowadays it becomes the core concern of chemists and biologists to screen and structurally design the compounds targeting G-quadruplex.This paper summarized the discoveries in the G-quadruplex-targeted telomerase inhibitors in recent years.
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Purpose:To study the activity of toremifene and its synergistic effect with anti-tumor drugs on human lung adenocarcinoma cell line A549,which might be expected to provide a new mode of therapy for the clinical management of lung cancer.Methods:The cytotoxic effects of these agents on human lung cancer cell line A549 were measured by a tet- razolium-based volorimetric assay (MTT assay).Results:Toremifene can inhibit the growth of A549 cell directly.The A value of the low dose toremifene combined with anti-tumor drugs were lower than that of anti-tumor drugs alone.Toremifene combined with VCR,ADM,DDP and VP-16 showed better effects.Conclusions:Toremifene combined with chemotherapy drugs shows significant synergistic anti-tumor effect on A549 cell.This might provide experimental evidence for lung cancer therapy.
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OBJECTIVE: To study the joint action of tea polyphenols and common anti-tumor drugs(vincristine,pingyangmycin,5-Fu,cisplatin) in inhibiting cell proliferation of the multiresistant HNE-1(200) cell line in patients with nasopharyngeal carcinoma after radiographic exposure.METHODS: The low toxic dosage of tea polyphenols and 4 kinds of anti-tumor drugs were optimized by MTT method.Then the inhibition ratio of multiresistant HNE-1(200) cell line treated by tea polyphenols and anti-tumor drugs waere detected.RESULTS: The low toxic dosage of tea polyphenols was 0.50 mg?mL-1.When the anti-tumor drugs were used in combination with tea polyphenols(0.50 mg?mL-1) as compared without,the inhibition ratio on HNE-1(200) cell line was increased by 100%～300%.CONCLUSIONS: Addition of tea polyphenols to anti-tumor drugs showed remarkable inhibitory effect on cell proliferation of HNE-1(200) cell line in patients with nasopharyngeal carcinoma,suggesting the reverse effect of tea polyphenols on resistant HNE-1(200) cell line.
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AIM Fas system plays an important role in the mechanism of immune escape and counterattack of colon cancer cells. This study was to investigate the influence of anti-tumor drugs on Fas, Fas ligand expressions on colon cancer cells. METHODS MTT method was used to get the inhibition concentration 50%(IC_ 50 ) of 5-fluorouracil (5-Fu), mitomycin (MMC), cisplatin (CP) to SW480. The concentrations of anti-tumor drugs were 0, 0.5 IC_ 50 , IC_ 50 , 2 IC_ 50 , respectively. Immmunocytochemical staining and flow cytometry analysis were used to detect the expression rates of Fas and FasL on SW480 cells before and after 5-Fu, MMC, CP treatments. In situ hybridyzation was used to observe Fas, FasL mRNA in SW480 cells before and after treatments. RESULTS IC_ 50 of 5-Fu, MMC, CP to SW480 were 11.70, 3.12, 3.40 mg?L -1 , respectively. Both immmunocytochemical staining and flow cytometry analysis found that without drug treatments SW480 expressed high FasL and low Fas, after the treatment of 5-Fu, Fas expression rates on SW480 increased but FasL remained unchanged; both Fas and FasL increased after the treatment of MMC or CP. In situ hybridization showed that after the treatment of 5-Fu and Fas mRNA on SW480 increased while FasL mRNA remained unchanged; both Fas mRNA and FasL increased after the treatment of MMC or CP. CONCLUSION Anti-tumor drugs can change the expression of Fas system on SW480 cells in different ways. MMC and CP can increase the sensitivity of colon cancer cells to apoptosis signals; at the same time, they possibly facilitate immune escape of tumor cells. However, 5-Fu does not have influence on immune escape of colon cancer cells. The target point is at the level of transcription or above it.-