The biotin synthesis pathway in Mycobacteria tuberculosis is a new target for the development of anti-tuberculosis drugs / 药学学报

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.

Prevalence of depression in healthcare workers of a COVID-19 First Line Treatment Centre in North Kerala

Background: The COVID-19 pandemic had a widespread impact over the health-care system all over the world. This had resulted in varying degrees of psychological issues on healthcare workers. Aim and Objectives: The aim of the study was to assess the prevalence of depression among healthcare workers of a COVID-19 first line treatment center (CFLTC). Materials and methods: In this cross-sectional study, 240 healthcare workers who volunteered for the study at COVID first line treatment centre-3 NIT mega boys’ hostel, Kozhikode, Kerala were recruited. They were interviewed, basic demographic data and patient health questionnaire-9 was administered. The data were analyzed with Microsoft Excel. The prevalence among various categories of healthcare workers were compared. Results: The prevalence of depression among healthcare workers was 52%. The prevalence of depression is each category of staff-doctors, staff nurses, cleaning staffs, and patient caretakers-separately. It was found that depression is inversely proportional to the knowledge, experience, medical qualification, and training. Conclusion: The prevalence of undetected depression is high among healthcare workers working in unconventional environment as in warfront situations such as COVID pandemic. The present study emphasizes the importance of proper screening of depression among healthcare workers in such circumstances in years to come.

Pharmacoeconomic evaluation of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer / 中国药房

OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.

Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

Drug resistance surveillance in Mycobacterium tuberculosis in Jiaxing City / 预防医学

Objective@#To investigate the resistance of Mycobacterium tuberculosis to first-line anti-tuberculosis drugs in Jiaxing City, Zhejiang Province from 2017 to 2019, so as to provide insights into improvements of the therapeutic effect of pulmonary tuberculosis. @*Methods@#Data pertaining to pulmonary tuberculosis in Jiaxing City from 2017 to 2019 were collected from the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, including demographics, treatment classification, sputum culture and drug resistance. The spectrum, types and prevalence of drug resistance in M. tuberculosis to four first-line tuberculosis drugs, including isoniazid (INH), rifampicin (RFP), streptomycin (SM) and ethambutol (EMB), was analyzed using a descriptive epidemiological method.@*Results@#A total of 1 310 M. tuberculosis isolates were cultured from pulmonary tuberculosis patients in Jiaxing City from 2017 to 2019, and there were 259 M. tuberculosis isolates that were resistant to anti-tuberculosis drugs, with an overall drug resistance rate of 19.77%. The prevalence rates of drug resistance to INH, SM, RFP and EMB were 13.36%, 11.83%, 5.50% and 3.59%, respectively. The prevalence of drug resistance was lower in M. tuberculosis isolates from treatment-naïve patients than from retreated patients (18.45% vs. 34.58%, P<0.05). M. tuberculosis isolates presented high resistance to SM (4.50%) and INH alone (4.35%), the highest resistance to INH-SM combinations (3.28%), and the highest resistance to INH+RFP+SM combinations (1.83%). Sixteen isolates were resistant to all the four drugs, with a drug resistance rate of 1.22%. The proportions of resistance to a single drug, RFP resistance, multidrug resistance and resistance to two and more drugs were 10.31%, 5.50%, 4.73% and 4.73%, respectively. In addition, the prevalence of RFP resistance among all patients and treatment-naïve patients both showed a tendency towards a rise from 2017 to 2019 (P<0.05). The prevalence of RFP resistance (7.01% vs. 3.76%) and resistance to two and more drugs (6.01% vs. 3.25%) was both higher among interprovincial mobile tuberculosis patients than among local non-mobile patients (P<0.05). @*Conclusions@#The overall prevalence of drug resistance was lower in M. tuberculosis isolates in Jiaxing City from 2017 to 2019 than in Zhejiang Province, with INH and RFP resistance as predominant types.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or metastatic esophageal carcinoma / 中国药房

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

Therapeutic Effect of Apatinib in First-line Treatment of Advanced Liver Cancer / 肿瘤防治研究

Objective To explore the effect of apatinib in first-line treatment of advanced liver cancer. Methods Retrospective analysis was performed on 35 patients with advanced liver cancer treated in our department from July 2017 to January 2020. All patients were given apatinib mesylate tablet 250-500 mg orally with QD. The patients with effective disease control (including CR, PR and SD) were given administration until PD or intolerance or death occurred. The primary endpoints were PFS and OS, and the secondary endpoints were DCR and ORR. The side effect was observed. Results There was one case of CR, 17 cases of PR and 11 cases of SD. The ORR and DCR were 51.43% and 82.86%. The median PFS and OS were 9.7 and 11.1 months. The main adverse reactions included hand-foot syndrome, hypertension, proteinuria, etc. Most grade 3-5 adverse reactions were reversible with good safety. Conclusion Apatinib can significantly improve the clinical benefits of liver cancer patients. It is an alternative first-line treatment for advanced liver cancer.

Economic Evaluation of Dexamethasone Combined with Rituximab for the First-line Treatment of Chronic Primary Immune Thrombocytopenia in Adults / 中国药房

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.

First-line treatment of castration-resistant prostate cancer with enzaluamine / 中华泌尿外科杂志

This case was a 75-year-old prostate cancer patient with multiple cardiovascular diseases. The clinical stage was T 3bN 1M 0.After regular follow-up with androgen deprivation therapy (ADT)(Goserelin+ bicalutamide), the PSA increased slowly at the 13th month, and at the 17th month, the trend of progression to castrated resistant prostate cancer (CRPC) was considered, combined with patients with a variety of cardiovascular diseases, we choose the first-line application of Enzaluamine treatment, the disease has been effectively controlled. Through the diagnosis and treatment of this case, we should consider not only the effectiveness and safety of the treatment, but also the influence and risk of the treatment to the cardiovascular disease.

Rituximab as First-line Therapy for Severe Pemphigus: A Case Series and Review of Current Literature

Summary@#Pemphigus refers to a group of life-threatening, autoimmune blistering disease that presents as blisters and erosions involving the skin and mucosa. Systemic corticosteroids and rituximab have been recommended as mainstay therapy for pemphigus vulgaris and pemphigus foliaceus. Herein, we report three cases of pemphigus vulgaris and a case of pemphigus foliaceus treated with rituximab as first-line therapy.

Neutropenic Fever in Lung Cancer: Clinical Aspects Related to Mortality and Antibiotic Failure / 中国肺癌杂志

BACKGROUND@#Lung cancer (LC) is the leading cause of cancer death. Patients treated with chemotherapy are at risk of developing chemotherapy-induced febrile neutropenia (FN), a potentially life-threatening complication. The aims of this study were (1) to characterize FN admissions of patients with LC in a pulmonology department, and (2) to determine associations between patient profiles, first-line antibiotic failure (FLAF) and mortality.@*METHODS@#Retrospective observational case-series, based on the analysis of medical records of LC patients that required hospitalization due to chemotherapy-induced FN.@*RESULTS@#A total of 42 cases of FN were revised, corresponding to 36 patients, of which 86.1% were male, with a mean age of 66.71±9.83 years. Most patients had a performance status (PS) equal or less than 1, and metastatic disease was present in 40.5% (n=17). Respiratory tract infections accounted for 42.9% (n=18) of FN cases, and multidrug-resistant Staphylococcus aureus was the most isolated agent. The mortality rate was 16.7% (n=7), and the FLAF was 26.2% (n=11). Mortality was associated with a PS≥2 (P=0.011), infection by a Gram-negative agent (P=0.001) and severe anemia (P=0.048). FLAF was associated with longer hospitalizations (P=0.020), PS≥2 (P=0.049), respiratory infections (P=0.024), and infection by a Gram-negative (P=0.003) or multidrug-resistant agent (P=0.014).@*CONCLUSIONS@#Lower PS, severe anemia, and infections by Gram-negative or multi-resistant agents seem to be associated with worse outcomes in FN patients.

Comparative efficacy and safety of first-line EGFR-TKIs for advanced non-small cell lung cancer：a network meta-analysis / 中华疾病控制杂志

Objective To compare the efficacy and safety of gefitinib, erlotinib, and afatinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods PubMed, EMBASE, and The Cochrane Library were searched to identify the relevant literatures published from December 2008 to December 2018. Bayesian network meta-analysis was carried out to rank the three treatments. Results A total of ten eligible studies involving 2275 patients were enrolled. In terms of efficacy, the surface under the cumulative ranking (SUCRA) indicated that erlotinib performed best in progression-free survival(PFS)(0.88), afatinib performed best in objective response rate(ORR)(0.82) and disease control rate(DCR) (0.86), gefitinib performed worst in PFS (0.45), ORR(0.42), and DCR(0.45). For safety, the differences of grade 3 or 4 adverse events rate (OR=0.29,95%CI:0.08-0.98) and discontinuation rate(OR=0.14,95%CI:0.01-0.8) between erlotinib and the platinum-based doublet chemotherapy were statistically significant. The ranking results also supported that erlotinib was the safest. SUCRA results suggested that gefitinib (0.31) had a lower grade 3 or 4 adverse events rate than afatinib (0.57), and the possibility of discontinuation in gefitinib (0.44) was similar to that of afatinib (0.41). Conclusion Erlotinib might be the preferred first-line treatment for advanced NSCLC after weighing and balancing the benefits and risks.

Research progression on the first-line biological target therapy of advanced / 中国肿瘤生物治疗杂志

@#With the progress of gene detection technology and the speed-up in new drug development, biological target therapy has fully covered the first-line treatment of advanced NSCLC. Immunotherapy has significantly improved the survival of advanced NSCLC patients with negative driven genes, and the median OS reaches about 2 years (15.6-30 months). EGFR is the most common driven gene. According to different EGFR mutation subtypes (L858R or 19del), different treatment mode (EGFR-TKI single drug, TKI combined with anti-vascular drugs and TKI combined with chemotherapy) is selected as the first-line treatment, which has become a consensus. Depending on the data of median PFS, the treatment efficacy against rare targets is more prominent, which has exceeded the efficacy of standard chemotherap:ALK (alectinib, PFS=34.8 months), ROS1 (ceritinib, PFS=19.3 months), RET (selpercatinib, PFS=18.4 months), BRAF (dabrafenib plus trametinib, PFS=14.6 months), NTRK (larotrectinib, PFS≥12 months) and MET (savolitinib, PFS=9.7 months). In conclusion, the first-line treatment of advanced NSCLC has entered the era of“precision-targeted treatment”based on different molecular typing, and it has become a consensus that high-throughput sequencing is required for newly diagnosed patients.

Patients experiences on the use of dihydroartemisinin piperaquine as an alternative first line artemisinin-based combination treatment for uncomplicated malaria in Northern Ghana

Background:Three different artemisinin-based combination therapies (ACTs) namely; artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine (being the latest to be introduced) are concurrently being used forthe treatment of falciparummalaria in Ghana. This study assessed patients’ experience, perceptions and willingness to use dihydroartemisinin-piperaquine, brand name duo-cotecxin as an alternative first line ACT for the treatment of falciparummalaria in Northern Ghana.Methods:This was a qualitative study using phenomenology approach where sixty in-depth interviews were conducted with two groups; thirty patients who were given duo-cotecxin, one group and thirty interviews with patients who were given other ACTs (artesunate-amodiaquine, artemether-lumefantrine) as another group. The interviews were conducted between August and November, 2015 Purposive sampling technique was used to select study participants. The interviews were transcribed andcoded into themes using QSR NVivo 11 software for thematic content analysis.Results:All patients who used duo-cotecxin reported that the drug was very good in treating uncomplicated malaria compared to other ACTs they had used in the past. Some of the patients who used other ACTs could not complete their doses because of the side effects. However, none of the patients who used duo-cotecxin reported side effects. The findings revealed high acceptance and preference to use duo-cotecxin to treat uncomplicated malaria compared with other ACTs. All the participants were also willing to recommend duo-cotexcin to their relatives and friends to use. Conclusions: Duo-cotecxin as an alternative first line ACT for treatment of uncomplicated malaria is highly accepted, preferred and there was willingness to use it compared with other first line recommended ACTs.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. RESULTS: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months). CONCLUSION: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

Association between the HER2 Gene Status and the Efficacy of First-line Pemetrexed Combined with Platinum Chemotherapy in Patients with Advanced Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma.@*METHODS@#The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed.@*RESULTS@#All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038).@*CONCLUSIONS@#HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.

Efficacy and safety of short course high-dose Dexamethasone as first-line treatment regimen for childhood newly diagnosed immune thrombocytopenia / 中华实用儿科临床杂志

Objective To compare the efficacy and safety of short course and high-dose Dexamethasone (HDD) and conventional Prednisone as first-line strategy for children newly diagnosed as primary immune thrombocytopenia (ITP).Methods This study analyzed pre-experimental data of a single center prospective randomized controlled clinical trial.Newly diagnosed but untreated ITP patients enrolled at the Department of Blood and Cancer Center,Beijing Children's Hospital,Capital Medical University from November 2016 to May 2017 were randomized into HDD group[Dexamethasone 0.6 mg/(kg · d),intravenous injection for 4 days] and Prednisone group [Prednisone 2 mg/(kg · d) for 14-28 days and then tapered within 1-2 months,the course of treatment less than 3 months].Initial response,sustained response and adverse effects after therapy were observed in 2 groups.Results Sixty-six children with ITP were included in the study:32 patients were in the HDD group and 34 patients were in the Prednisone group.Two groups were matched in the baseline characteristics including gender,age,platelet counts and disease course before therapy and bleeding assessment (all P ＞ 0.05).The initial response (the response of HDD group within 10 days of treatment and Prednisone group within 28 days of treatment):overall initial response had no statistical difference between the HDD group and the Prednisone group[90.6％ (29/32 cases) vs.100.0％ (34/34 cases),x2 =1.528,P ＞ 0.05].HDD group had a lower incidence of complete response compared with that in the Prednisone group [54.4％ (19/32 cases) vs.94.1％ (32/34 cases),x2 =11.330,P =0.001];median time of response in two groups showed no statistically difference (2 d vs.1 d,Z =-0.149,P ＞ 0.05).There was no significant difference in the recovery of skin and mucosal bleeding after treatment between the Dexamethasone group and the Prednisone group (Z =-1.413,-1.031,all P ＞ 0.05).The sustained response (the response lasted for up to 6 months and above):overall and complete sustained response had no statistically difference between the HDD group and the Prednisone group [92.9％ (26/ 28 cases) vs.85.3％ (29/34 cases),P =0.594;78.9％ (15/19 cases) vs.81.3％ (26/32 cases),P=1.000].Log-rank test showed no significant difference in the duration of response between 2 groups (P =0.341).The side effects in the Prednisone group included weight gain or Cushing sign (94.1％) and mental and emotional changes (23.5％);in the HDD group 15.6％ of children had infection,without other glucocorticoid-related side effects.There was no significant difference in the incidence of infection between two groups[15.6％ (5/32 cases) vs.26.5 ％ (9/34 cases),P =0.281].All of the above infections were of respiratory tract infections and mild gastrointestinal infections.Conclusions Efficacy of the HDD group in the initial and sustained responses is similar,but side effects were apparently lower compared with that in the Prednisone group.However,a large multicenter randomized controlled clinical study is necessary to confirm this result.