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.

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), χ2=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), χ2=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.

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.

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.

Ki-67 expression affects the clinical therapeutic effect on advanced lung adenocarcinoma / 医学研究生学报

Objective The expression level of the Ki-67 protein is a marker of the poor prognosis in non-small-cell lung cancer. This study explored the correlation of the Ki-67 expression level with the clinical efficacy in the treatment of advanced lung adenocarcinoma.Methods From January 2015 to December 2015, 92 patients with stage Ⅳ lung adenocarcinoma were treated in the Department of Respiratory and Critical Care Medicine of Nanjing General Hospital, 65 with oral gefitinib for EGFR mutation-positive or crizotinib for ALK positive (the targeted therapy \[TT\] group) and the other 27 with pemetrexed + cisplatin or nedaplatin (the chemotherapy \[CT\] group). The expression of Ki-67 was determined by immunohistochemistry, its relationship with the clinicopathological features and therapeutic effects was analyzed, and the progression-free survival (PFS) was calculated.Results Ki-67 was expressed lowly in 43 (46.7%) and highly in 49 (53.3%) of the cases. The median PFS after treatment was significantly longer in the patients with a low than in those with a high Ki-67 expression in the TT group (10 vs 7 mo, P<0.05) and in the CT group as well (8 vs 7 mo, P<0.05). Ki-67 (HR=1.011, 95% CI: 1.000-1.023) and ALK (HR=0.325, 95% CI: 0.112-0.942) were shown to be predictive factors of poor PFS.Conclusion The expression level of Ki-67 affects the effect of clinical treatment, especially that of the first-line targeted therapy, on advanced lung adenocarcinoma.

FOLFOX/XELOX plus cetuximab administered weekly versus biweekly as a first-line treatment for patients with KRAS/RAS wild-type metastatic colorectal cancer: a retro-spective study / 中国肿瘤临床

To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.

Precision first-line therapy for advanced non-small-cell lung cancer patients harboring EGFR mutation / 中华肿瘤杂志

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the preferred treatment option for advanced non-small-cell lung cancer (NSCLC) patients with activating mutations in epidermal growth factor receptor (EGFR) according to major practice guidelines. Gefitinib, elortinib and icotinib formed the cornerstone of first-line EGFR-TKIs in the clinical practice in our country. Now, with the continuously emerging of new types of EGFR-TKIs and ever-increasing publication of clinical trial results on afatinib, AZD9291 and other TKIs, we have more first-line choices for patients with EGFR mutations. Meanwhile, the development of gene detection technology is facilitating investigators to get insights on the molecular biological behavior of NSCLC and to elucidate the mechanism of drug resistance. This review will focus on precision first-line therapy for advanced NSCLC patients harboring EGFR mutation.

Advances in personalized treatment of small cell lung cancer / 中国肿瘤临床

Small cell lung cancer (SCLC) is a lethal malignancy characterized by rapid growth, early metastatic spread, and unfavorable survival outcomes. Optimizing treatment for patients with SCLC has been the focus for investigators. The emergence of precision medi-cine and personalized treatment brought significant breakthroughs into SCLC treatment and changed the therapeutic model. The de-velopment of molecular bioinformatics increased our understanding of complex molecular mechanisms of SCLC, and novel targets for personalized treatment have been developed. Clinical trials testing these targets are ongoing, which show the potential of personal-ized treatment for SCLC.

Advances in chemotherapy of small cell lung cancer / 中国肿瘤临床

Small cell lung cancer (SCLC) accounts for about 13%of lung cancer. SCLC exhibits an early metastatic potential and sensitivi-ty to first-line cytotoxic chemotherapy compared with non-small cell lung cancer. Current treatments include surgery, radiotherapy, and chemotherapy. Platinum plus etoposide is viewed as the standard first-line chemotherapy. However, recurrence rate of cancer af-ter platinum plus etoposide chemotherapy is high. Topotecan monotherapy is the standard second-line chemotherapy. Meanwhile, novel targeted immunotherapy showed poor effects. Hence, new breakthroughs in the treatment of SCLC are urgently needed.

Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.

Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.

Gefitinib in first-fine therapy for 34 cases of advanced non-small cell lung cancer / 中国癌症杂志

Background and purpose: It has been proven that gefitinib can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) as a molecule targeted drug. This research was aimed to investigate the efficacy and toxicity of gefitinib as the first-line therapy for advanced NSCLC. Methods: A total of 34 pathologically-confirmed NSCLC patients who were not willing to receive or tolerate traditional cytotoxic drug chemotherapy were enrolled into the study. Gefitinib was orally administered 250 mg daily until disease progression or the occurrence of intolerable toxicity. Results: The objective response rate of gefitinib was 29.4%. The disease control rate was 61.8%. The rate of symptom relief was 47.1%. The median progression-free survival was 3.0 months. The median overall survival was 10.2 months. One-year survival rate was 35.3%. The objective response rate of nun-smoker was higher than smoker (P=0.023). The disease control rate for the patients with rash toxicity after administration of the drug were higher than those without rash (P=0.005). Logistic regression showed that rash was an independent disease control factor (P=0.003). The most common drug-related adverse events were rash and diarrhea. Conclusion: Gefitinib provided another choice to patients who are unwilling or unable to be treated by chemotherapy.