Treatment Of Chinese Patients Research Articles

Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China.

This study was designed to evaluate the efficacy of isolated limb infusion (ILI) treatment in Chinese patients with in-transit melanoma and to identify factors predictive of the outcome. A total of 150 patients with in-transit melanoma who received a single ILI between 2007 and 2016 were identified from a prospectively collected database. All patients had AJCC Stages IIIb, IIIc, and IV disease. Acral lentiginous melanoma (ALM) accounted for 79% of patients, and 59% had a high burden of disease (BOD). The complete response (CR) and partial response (PR) rates were 6 and 35%, respectively. Forty-five percent of patients experienced grade III-IV limb toxicities, but no grade V toxicity was observed. Patients with a low BOD, high limb temperature, high peak creatine phosphokinase (CK) level, and grade III-IV limb toxicity achieved higher response rates. Stage IV disease and high BOD were associated with worse infield progression-free survival (PFS) and overall survival (OS), whereas patients with CR or PR to ILI had better infield PFS and OS. Multivariate analyses showed that disease stage, BOD, and a CR were independent predictors of infield PFS, whereas disease stage and a response to ILI were independent predictors of OS. ILI is well-tolerated but the response rate in Chinese patients was lower than that reported in US and Australian studies. The prevalence of the ALM histological type, advanced disease stages, and a high BOD may be the main reasons for this. A response to ILI, BOD, and disease stage are prognostic factors for survival.

Long-Term Efficacy and Safety of Interferon Alpha-2a in the Treatment of Chinese Patients with Behçet’s Uveitis Not Responding to Conventional Therapy

ABSTRACTPurpose: To investigate the long-term efficacy and safety of interferon alpha-2a (IFNα-2a) in Chinese patients with Behçet’s uveitis (BU) refractory to conventional therapy.Methods: In a prospective observational cohort study, 127 patients were treated with an initial dosage of 3 million units per day in the first three months, followed by gradual tapering of the dose.Results: After 3 months of treatment, IFNα-2a was shown to be effective in 115 cases (91%). At the end of the 1-year follow-up, the frequency of ocular relapses decreased to 1.59 ± 1.68 per year (ranging 0–6) (p < 0.001), as compared to 5.09 ± 2.51 per year (ranging 3–15). Moreover, the frequency of oral ulcer relapses also decreased to 2.49 ± 1.84 per year (ranging 0–6) (p < 0.001), as compared to 8.20 ± 3.72 per year (ranging 2–10). Visual improvement or stability was observed in 32 patients (59%) in these 54 patients. During a mean follow-up of 11 months (range 3–33), the mean final VA (logMAR) had progressed from 1.0 logMAR to 0.8 logMAR in all treated patients.Conclusions: Long-term low dose of IFNα-2a is useful in treating Chinese BU patients who do not respond adequately to conventional therapy.

Cost Effectiveness of Imatinib, Dasatinib, and Nilotinib as First-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia in China.

Tyrosine kinase inhibitors (TKIs) have obvious effects on chronic myeloid leukemia (CML), but they are expensive in China. Moreover, the overall cost of treatment of CML is high and the medical economic burden of patients with CML on the government is heavy. This study tested the cost effectiveness of imatinib, nilotinib, and dasatinib as first-line treatment in Chinese patients who were first diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). A state-transition Markov model combining clinical effectiveness, utility, and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. The imatinib-first, dasatinib-first, and nilotinib-first strategy offered patients 9.76, 9.87, and 9.72 quality-adjusted life years (QALYs) at a cost of US$303,502.42, US$381,681.03, and US$305,509.92 over 20years, respectively. The nilotinib-first strategy exhibited the lowest utility and highest price and was thus eliminated. An incremental cost-effectiveness analysis of the imatinib-first strategy and the dasatinib-first strategy showed that the dasatinib-first strategy yielded an incremental cost-utility ratio (ICER) of 710,714.64 $/QALY compared with the imatinib-first strategy, which exceeded the threshold; hence, the dasatinib-first strategy was not cost effective and was eliminated. The results were robust for multiple sensitivity analyses. From the perspective of the Chinese medical system, imatinib is likely to be more cost effective than dasatinib and nilotinib for patients who were first diagnosed with CML-CP.

Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model

Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout (TGF-βRIICol2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRIICol2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRIICol2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF-β/Smad signaling activation, and be considered a good option for the treatment of osteoarthritis.

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial

IntroductionAvailable data show that approximately 8%–18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for...

Recombinant humanised anti-PD-1 monoclonal antibody (JS001) treatment for patients with refractory or metastatic nasopharyngeal carcinoma: preliminary results of an open-label, phase 1b/2, clinical study

BackgroundPatients with unresectable or recurrent nasopharyngeal cancer who have disease progression after standard therapy have few treatment options and represent an important, unmet medical need. Nasopharyngeal cancer is closely associated with Epstein-Barr virus (EBV) infection and has been reported to have high concentrations of PD-L1 expression and tumour-infiltrating lymphocytes, which indicate a potential implication of PD-1 blockade in the treatment of nasopharyngeal cancer. JS001, a humanised recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1, with its ligands PD-L1 and PD-L2, and promotes antigen-specific T-cell activation. Results of a phase 1 study of JS001 treatment in Chinese patients with heavily pretreated solid tumours have shown an acceptable safety profile in doses up to 10 mg/kg once every 2 weeks until progressive disease, intolerance, withdrawal of consent, or investigator decision. Here we report the safety and efficacy of JS001 in a phase 1b/2 clinical study. MethodsWe did this open-label, phase 1b/2, clinical study in Chinese patients with refractory or metastatic nasopharyngeal cancer received JS001 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to the immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) criteria. Tumour PD-L1 expression, plasma EBV DNA concentration, and additional potential predictive biomarkers were monitored for correlation with clinical response. This study is registered with ClinicalTrials, number NCT02915432. FindingsBetween Dec 29, 2016, and June 19, 2017, we enrolled 48 patients with nasopharyngeal cancer. Of 23 evaluable patients, the median age was 46 years (range 33–70), 81% were male, and EBV serology tested positive in 92%. Adverse events occurred in 46 (96%) of 48 patients, which were mostly grade 1 or 2. Grade 3 and worse adverse events occurred in 17 patients (35%), including abnormal liver function (n=6, 13%), dysphagia (n=2, 4%), and pulmonary infection (n=2, 4%). Rapid and deep clinical responses were observed. Seven patients (15%) had partial responses while ten patients (21%) achieved stable disease, with the proportion of patients who achieved an objective response of 30% and a disease control of 73%. The responses seemed unrelated to PD-L1 expression status on tumour biopsy. InterpretationJS001 treatment has shown good clinical activity in heavily pretreated patients with nasopharyngeal cancer and a manageable safety profile. We plan to enrol 54 patients with nasopharyngeal cancer to further monitor the safety and efficacy of JS001 treatment. FundingShanghai Science and Technology Innovation Fund.

Upper Gastrointestinal Complications and Cardiovascular/Gastrointestinal Risk Calculator in Patients with Myocardial Infarction Treated with Aspirin.

Background:Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator.Methods:The MI patients who visited Shapingba District People's Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events.Results:A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774–0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93.1%, respectively, for predicting gastrointestinal events in Chinese patients with MI.Conclusions:AsaRiskCalculator had a predictive value for gastrointestinal events in Chinese patients with MI. HP infection seemed to be an independent risk factor for gastrointestinal events caused by long-term aspirin treatment in Chinese patients with MI, and it should be included in the risk calculator adapted for Chinese patients.

Safety and efficacy of paliperidone palmitate 1-month formulation in Chinese patients with schizophrenia: a 25-week, open-label, multicenter, Phase IV study.

RationaleLong-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.ObjectiveThe aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.MethodsIn this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).ResultsOf the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, −27.2 [18.30]; P<0.0001). The Clinical Global Impressions-Severity and Personal and Social Performance scores (secondary end points) also improved significantly (P<0.0001). At 6 months, PP1M had a positive impact on medication satisfaction, adherence, and increased preference for LAIs. Treatment-emergent adverse events (TEAEs) were reported by 181 (51.3%) patients (TEAEs ≥5%: extrapyramidal disorder [15.3%], akathisia [10.5%], blood prolactin increase [8.8%], insomnia [5.4%]). A total of 8 deaths were reported, including 4 completed suicides.ConclusionLong-term treatment with PP1M was efficacious, and no new safety concerns were identified in Chinese patients with schizophrenia. Overall, the results were comparable with observations from previous studies.

A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non-inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients with schizophrenia and acute episodes

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were −33.4 for quetiapine XR and −35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, −9.9 ± 0.53 and −11.1 ± 0.51; negative subscale, −5.9 ± 0.50 and −6.7 ± 0.48; general psychopathology subscale, −12.9 ± 0.74 and −13.9 ± 0.71; aggression and hostility cluster scores, −4.8 ± 0.33 and −5.4 ± 0.32; and depression cluster scores, −1.8 ± 0.18 and −1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease

BackgroundGenetic variation of matrix metalloproteinase 9 (MMP-9) gene polymorphism has been suggested to modulate coronary heart diseases (CHD), yet the underlying mechanisms are not well understood.MethodsWe investigated the association of MMP9 rs3918242 single nucleotide polymorphism with inflammation and lipid-lowering efficacy after simvastatin treatment in Chinese patients with CHD. Fasting serum lipid profile and plasma inflammatory mediators were determined at baseline in 264 patients with CHD and 186 healthy control subjects, and after HMG-CoA reductase inhibitor simvastatin treatment (20 mg/day) for 12 weeks in CHD subjects.ResultsWe found that plasma MMP-9, TNF-α and IL-10 levels were significantly elevated in patients with CHD compared to control subjects before treatment. The plasma MMP9 in CHD patients carrying rs3918242 CC, CT and TT genotypes were comparable. Interestingly, CHD patients carrying TT genotype had significantly higher level of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) than those carrying CC genotype (P <0.05). Simvastatin treatment significantly reduced LDL-C, TG and plasma inflammatory mediator levels in CHD patients. The reduction of LDL-C upon simvastatin therapy was significantly greater in patients carrying TT genotype than those carrying CC genotype (P <0.05).ConclusionsMMP9 rs3918242 TT genotype is associated with elevated serum TG and LDL-C, and enhanced LDL-C-lowering response upon simvastatin treatment in Chinese patients with CHD.Clinical trial registrationThis study was retrospectively registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-ROC-17010971) on March 23rd 2017.

Post-Hoc Study: Intravenous Hydration Treatment in Chinese Patients with High Risk of Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention

Contrast-induced nephropathy (CIN) develops after the injection of iodinated contrast media. This is a post hoc analysis of the data obtained from the TRUST study, which was a prospective, multicentre, observational study conducted to evaluate the safety and tolerability of the contrast medium iopromide in patients undergoing cardiac catheterization from August 2010 to September 2011 in China, conducted to explore the current status, trends and risk predictors of hydration treatment. The status of hydration to prevent CIN in each patient was recorded. Of the total 17,139 patients from the TRUST study (mean age, 60.33 ± 10.38 years), the overall hydration usage was 46.1% in patients undergoing percutaneous coronary intervention (PCI) and 77.4%, 51.7%, and 48.5% in patients with pre-existing renal disease, diabetes mellitus, and hypertension, respectively. The proportion of hydration use increased from 36.5% to 55.5% from August 2010 to September 2011, which was independently associated with risk predictors like older age, pre-existing renal disease, hypertension, diabetes mellitus, prior myocardial infarction, ST segment elevation MI, high contrast dose, multi-vessel disease and reduced LVEF (<45%). Overall, the usage of intravenous hydration treatment for patients with a high risk of CIN following PCI was high in China.

Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia.

Background:The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).Methods:Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.Results:The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3–6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).Conclusions:This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.

Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is known to overexpress somatostatin receptors (SSTRs), most commonly SSTR2 and SSTR5. The expression of SSTRs on tumor cells forms the basis for somatostatin analog treatment of patients with NEN. The present study detected the expression of SSTR2 and SSTR5 in GEP-NEN and investigated the efficacy and safety of octreotide long-acting release (LAR) in the treatment of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET) in China. The present study reported that functionality of the pancreas, G1 and G2 grading, NET classification and Tumor-Node-Metastasis stages I and II were associated with higher SSTR2 positive expression. Similarly, SSTR5 was increased in pancreatic and well-differentiated tumors. SSTR2 and SSTR5 positive expression predicted improved survival in GEP-NEN patients. The median overall survival of patients treated with octreotide LAR was not reached. The median time to progression was 20.2 months, with the objective response rate being 5.6% and the stable disease rate being 79.6%. A total of 25.9% of the patients experienced adverse drug reactions. In conclusion, the present study demonstrated that SSTR2 and SSTR5 are heterogeneously expressed in GEP-NEN. Both markers may serve as potential prognostic factors. Octreotide LAR is effective and safe in the treatment of Chinese patients with advanced GEP-NET.

P2.03a-019 A Retrospective Analysis Of Nanoparticle Albumin Bound Paclitaxel In Chinese Patients With Recurrent Advanced Non-small Cell Lung Cancer In A Single Center

This is the first report describing the safety and short-term efficacy of nanoparticle albumin bound paclitaxel (Nab-PTX) as monotherapy administered weekly in the treatment of Chinese patients with recurrent advanced non-small cell lung cancer (NSCLC), and analyzing potential factors that may affect prognosis. Patients with recurrent advanced NSCLC who received an weekly nab-paclitaxel regimen (130 mg/m2/week) treatment were eligible. Toxicity and response according to the RECIST criteria were summarized in the study. Classification and regression tree (CART) analysis was performed to estimate the effect of variables (age, gender, performance score, smoking, clinic stage, pathological type, previous line of therapy, treatment cycles, EGFR status, EGFR-/ALK-TKIs, SPARC expression) on PFS. The Kaplan–Meier analysis was used to estimate the effect of terminal tree notes. A total of 104 patients were included in the study from June 2010 to March 2014 in the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences,. The median follow-up period was 9.56 months (0.92-34.00 months). The overall response rate was 21.4%, and the disease control rate was 73.8%. The median PFS was 4.53 months (95% CI: 3.518- 5.542), and the median OS was 12.53 months (95% CI: 10.502- 14.558). Grade 3 adverse events were neutropenia (8.8%), peripheral neuropathy (4.8%), myalgia/arthralgia (4.0%), and fatigue (1.9%), respectively. Grade 4 toxicities rarely occurred except neutropenia (1.0%). CART analysis identified 4 terminal nodes based on therapy cycles, age and therapy line. In the four subsets, those with ＜ 4 therapy cycles had the lowest PFS (Median: 1.80 months). Those with ≥ 4 cycles and age ≥70 years had the longest PFS (Median: 8.83 months). The median PFS was significantly different between the four subgroups (P =0.000). In addition, PFS in the ≥ 4 therapy cycles group was better than the without group (Median: 6.23 vs. 1.80 months, P=0.000). No PFS significant differences were observed for both age (≥70 years vs ＜70 years; Median: 8.83vs. 5.87 months, P=0.06) and lines of therapy (＞third-line vs ≤ third-line; Median: 6.37 vs 4.60, P=0.063). A trend of a benefit in PFS in favor of ≥70 years age and ＞third-line groups was found in our treatment. The weekly Nab-PTX regimen was effective and well-tolerated in patients with recurrent advanced NSCLC. Treatment cycles factors may be used to predict the therapeutic efficacy of Nab-PTX. Nab-PTX was also found the favorable survival benefit in older population (aged ≥70 years) and patients with ＞third-line therapy.

The efficacy and safety of cardiac contractility modulation in patients with nonischemic cardiomyopathy: Chinese experience

Background: Cardiac contractility modulation (CCM) has been used in patients with heart failure and normal QRS duration to improve exercise tolerance and quality of life. The safety and efficacy of CCM have been previously tested in moderate to severe heart failure patients with various etiologies in the western population. However, limited data are available on the safety and efficacy of CCM in Chinese patients with dilated cardiomyopathy and heart failure. Methods: Eight patients with dilated cardiomyopathy were prospectively enrolled to receive CCM implants from 5 hospitals in China. All patients had the New York Heart Association (NYHA) functional class III and IV heart failure, with left ventricular ejection fraction (LVEF) ≤35%, and QRS ≤ 120 ms. All patients were followed up at the 3rd and 6th month. Evaluation included the NYHA functional class, 6-min hall walk test (6MHW), Minnesota Living with Heart Failure (MLWHF) Questionnaire, and CCM parameters. Results: CCM was successfully implanted in all eight patients (50 ± 11 years, 6 men), and no device-related complications were observed in all patients at 3- and 6-month follow-up besides one patient voluntarily received heart transplantation at the 2nd month after CCM implantation and died from intracerebral hemorrhage during the perioperative period. Compared with baseline, the NYHA functional class (ΔNYHA: −1.0–−3.0, P= 0.016), the MLWHF quality of life scores (ΔMLWHF: −21.1 ± 17.5, P= 0.019), and 6MHW (Δ6MHW: 207.4 ± 202.5 m, P= 0.035) were significantly improved at 3-month follow-up. No significant change was observed in LVEF (ΔLVEF: −0.5%, 95% CI: −2.0%–12%, P= 0.813). All of these evaluations at 6-month follow-up were similar to those observed at 3-month, and no further improvement were observed from 3- to 6-month follow-up in the NYHA functional class (ΔNYHA 0; 0–1.0, P= 0.999), 6MHW (Δ6MHW: 39.2 ± 70.4 m, P= 0.231), MLWHF quality of life score (ΔMLWHF: 2.7 ± 3.9, P= 0.158), and LVEF (ΔLVEF: 2.0%, 95% CI: −2.0%–7.0%, P= 0.313). Conclusions: CCM might be a new choice of device treatment for Chinese patients with nonischemic cardiomyopathy and heart failure if they have normal QRS duration.

Antiplatelet Strategies and Outcomes in Patients with Noncardioembolic Ischemic Stroke from a Real-World Study with a Five-Year Follow-Up.

Aspirin and clopidogrel are both acceptable antiplatelet options for the secondary prevention of noncardioembolic ischemic stroke. Associations between Essen Stroke Risk Score (ESRS) and antiplatelet treatment in Chinese patients with noncardioembolic ischemic stroke were assessed. This retrospective study was taken in a tertiary care hospital located in eastern China. Patients with noncardioembolic ischemic stroke hospitalized during January 1, 2009, to December 31, 2011, were classified according to ESRS during index stroke hospitalization. Antiplatelet strategy at the time of discharge was categorized as aspirin (100mg/day) vs. clopidogrel (75mg/day). Patients received follow-up from July 1, 2014, to December 31, 2015, and the efficacy of clopidogrel and aspirin in different ESRS subgroups was assessed with respect to reducing the risk of a combined vascular event of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage. Totally, 1175 non-cardiac stroke patients were included, among which 878 patients completed follow-up surveys. Of the patients who completed the follow-up, 458 (52.2%) had an ESRS>3, and 621 (70.7%) received aspirin. Patients who received clopidogrel tended to be older, and more patients had hypertension, diabetes, and an ESRS>3 than patients who received aspirin. Over a mean follow-up of 5.2years, the rate of combined vascular events was 19.3% in the aspirin group and 16.7% in the clopidogrel group. Compared with clopidogrel-treated patients, a significant (P=0.044) reduction in combined vascular events in aspirin-treated patients was observed in patients with an ESRS≤3 (OR, odds ratio 0.5; 95% CI 0.3 to 0.9). However, a significant (P=0.002) increase in combined vascular events was observed in patients with an ESRS>3 (OR 2.2; 95% CI 1.3 to 3.8). More clopidogrel-treated patients with ESRS<3 and ESRS=3 discontinued treatment than their counterparts who took aspirin (P<0.05). Adverse drug events, such as digestive discomfort and bleeding, were similar. In conclusion, clopidogrel is suggested for patients with an ESRS>3 and aspirin for patients with an ESRS≤3 for the secondary prevention of noncardioembolic ischemic stroke in Chinese patients.

123 Possible Factors Affecting Efficacy of Dapoxetine 30mg Treatment in Chinese Patients With Premature Ejaculation

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI) and it is the first drug approved in China for on-demand treatment of premature ejaculation (PE). An integrated analysis of 5 Phase III trials showed that >60% of patients treated with dapoxetine reported that their PE was at least “slightly better”. However, the effect of dapoxetine on Chinese patients with PE has been seldom reported. The aim of this study was to evaluate the effect of treatment with dapoxetine 30 mg on-demand on Chinese patients with PE. Possible factors that may affect dapoxetine treatment efficacy were also investigated. This retrospective, open, observational study included 172 patients with PE. The patients were assessed using a detailed medical, sexual and PE treatment history. Patients received dapoxetine therapy (30 mg on-demand) for 4 weeks, and then followed in outpatient clinic visits or by telephone. Data on premature ejaculation diagnostic tool (PEDT), self-reported intravaginal ejaculatory latency time (IELT), intromission frequency, premature ejaculation profile (PEP), and clinical global impression of change (CGIC) were recorded. Patients were divided into “CGIC=0” and “CGIC≥1” accordingly. Baseline clinical data were compared between these 2 groups to determine possible factors that may affect dapoxetine treatment effectiveness.

202 Efficacy and Tolerability of Dapoxetine in the Treatment of Chinese Patients With Premature Ejaculation

202 Efficacy and Tolerability of Dapoxetine in the Treatment of Chinese Patients With Premature Ejaculation

Development of a Novel Prognostic Scoring System of Time to First Treatment for Chinese Patients with Chronic Lymphocytic Leukemia

Background: The established clinical staging systems (Rai/Binet) of chromic lymphoma leukemia (CLL) had limitedly discriminated among prognostic groups, especially for the patients in early stages and without treatment indications. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated the prognostic improvement of the combination of more markers together. In order to predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional bio-markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index.Patients and Methods: Taking advantage of a population of 402 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months (ms). Multivariable statistics were applied with software SPSS 17.0, and the end point was TTFT.Results: Based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (Rai risk group), 17p deletion and unmutated IGHV. Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups [low risk (score 0), intermediate low (score 1), intermediate high (score 2) and high risk (score 3-6)] with significantly different TTFT (median TTFT of NR, 65.0 ms, 36.0 ms and 19.0 ms, respectively, p<0.001).Conclusions: This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers (IGHVmutation status, 17p deletion) with traditional clinical stage (Rai staging system). This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL. DisclosuresNo relevant conflicts of interest to declare.

Open-Label Study of Bendamustine Hydrochloride in Chinese Patients with Indolent Non-Hodgkin Lymphoma (NHL) Refractory to Rituximab Treatment

Introduction: The addition of rituximab to chemotherapy has been associated with substantial responses in patients with indolent NHL, but patients usually relapse. Bendamustine hydrochloride (bendamustine; Treanda®) is an alkylating agent approved globally for multiple indications including chronic lymphocytic leukemia, indolent B-cell NHL, mantel cell lymphoma, and multiple myeloma. This open-label, single-arm, multicenter study in China aims to determine the overall response rate (ORR) to bendamustine treatment in patients with indolent B-cell NHL refractory to a rituximab-containing regimen.Methods: Patients with documented relapse from indolent B-cell NHL after rituximab treatment and 1-3 previous chemotherapy regimens were included. Patients received bendamustine intravenous 120 mg/m2 infusion (over 60 minutes) on day 1 and 2 of each 21-day cycle for at least 6 cycles and were allowed to continue treatment for up to 8 cycles. Primary endpoint was response rate based on the modified International Workshop Response Criteria; secondary endpoints were duration of response (DOR), progression-free survival (PFS), and safety.Results: A total of 102 patients from 20 centers were enrolled. All enrolled patients were analyzed for safety and efficacy. The ORR was 73% (95% CI: 62.82-80.92) per independent review committee (IRC) including 19% complete response (CR) and 54% partial response (PR). The ORR per investigator assessment was 78% (30% CR and 48% PR). Among 31 patients with disease refractory to last alkylator therapy, the ORR was 68% (95% CI: 48.63-83.32). The median DOR was 16.5 months (95% CI: 10.9-NA) per IRC and 12.5 months per investigator. Durable responses were observed across all baseline patient and disease characteristics. Median DOR was not reached in patients refractory to last alkylator or chemotherapy treatment. The median PFS was 18.6 months and was similar across baseline characteristics. Disease characteristics did not significantly impact PFS.The overall safety profile was consistent with known adverse events (AEs). The most common AEs (≥40%) were white blood cell count decreased (54%), neutrophil count decreased (47%), neutropenia (46%), leukopenia (45%), nausea (44%), and platelet count decreased (40%). Most patients completed planned treatment; the mean relative dose intensity was 82%. Neutropenia was the most common reason for dose reductions. Four patients died during the study, three of which were attributed to bendamustine. At least one serious AE was experienced by 29 patients, and AEs that resulted in discontinued treatment occurred in 25 patients.Conclusions: Single-agent bendamustine is effective in the treatment of Chinese patients with rituximab-refractory, relapsed indolent B-cell NHL including those with previous alkylator exposure, with a safety profile consistent with known AEs.Sponsor: Teva Branded Pharmaceutical Products R&D DisclosuresMueller:Teva Pharmaceuticals, Inc.: Employment, Equity Ownership.