Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

PHASE II CLINICAL TRIAL OF LASTET CAPSULE IN COMBINATION CHEMOTHERAPY OF MALIGNANT TUMORSIN CHINA

This study reports the efficacy of prolonged administration of oral etoposide in the treatment of 86 cases with solid tumor,malignant lymphoma and other cancer.The oral etoposide used was the Lastet capsule (Las-c).An overall response rate(RR)of 62.8% was achieved with CR rate being 23.3% and PR rate 39.5%. Different combination chemotherapy regimens led to different response rates but no significant difference was found. The Las-C containing regimens used in this study have not caused any serious side effects.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with High-Grade Glioma. Final Report (Protocol BT-06), and Review of Recent Trials

Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Recurrent Glioblastoma Multiforme: Final Report (Protocol BT-21)

Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five?and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in?8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Recurrent, Refractory or Progressive Primary Brain Tumors—Final Report (Protocol BT-22)

Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Low-Grade Astrocytomas—Final Report (Protocol BT-13)

Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.

Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Primary Brain Tumors—Final Report (Protocol BT-09)

Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.

重组人粒细胞巨噬细胞集落刺激因子预防白细胞减少的II期临床试验

目的：为研究国产重组人粒细胞巨噬细胞集落刺激因子（ｒｈ Ｇ Ｍ＿ Ｃ Ｓ Ｆ， 商品名里亚尔） 防治实体瘤化疗所致白细胞（ Ｗ Ｂ Ｃ） 和绝对中性粒细胞计数（ Ａ Ｎ Ｃ） 减少的临床效果及不良反应。方法：采用多中心随机分组、自身交叉对照方法，进行了临床 Ｉ Ｉ期试验。６０ 例肿瘤化疗病人随机均分 Ａ Ｂ 组和 Ｂ Ａ组。 Ａ Ｂ 组第１ 周期化疗加ｒｈ Ｇ Ｍ＿ Ｃ Ｓ Ｆ 治疗（ 治疗组） ，第２ 周期单用化疗（ 对照组） ； Ｂ Ａ 组第１ 周期单用化疗，第２ 周期化疗加ｒｈ Ｇ Ｍ＿ Ｃ Ｓ Ｆ 治疗。５６ 例可供临床疗效分析。结果：ｒｈ Ｇ Ｍ＿ Ｃ Ｓ Ｆ 可减轻化疗所致 Ｗ Ｂ Ｃ 和 Ａ Ｎ Ｃ 下降程度，缩短 Ｗ Ｂ Ｃ 和 Ａ Ｎ Ｃ 降至正常值以下的持续时间，促进 Ｗ Ｂ Ｃ 和 Ａ Ｎ Ｃ 减少的早日恢复，有助于化疗按期进行。主要不良反应有轻、中度发热，注射部位疼痛，骨、肌肉疼痛，乏力。少见的有皮疹、寒战、流涕、胸闷、心悸，一般可以耐受。结论：ｒｈ Ｇ Ｍ＿ Ｃ Ｓ Ｆ 是有价值的化疗辅助药物。

PTPRZ1-METFUsion GENe(ZM-FUGEN)trial:study protocol for a multicentric,randomized,open-label phase II/III trial

Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with chinadrugtrials.org.cn(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with chinadrugtrials.org.cn(CTR20181664).

GCP药师在抗肿瘤药物临床试验配置管理中的作用

目的临床试验中抗肿瘤药物的配置与普通药物不同。近年来,抗肿瘤新药临床试验越来越多,在试验过程中,抗肿瘤药物的配置管理工作也越来越重要。该文主要探讨GCP药师在Ⅱ期、Ⅲ期抗肿瘤药物临床试验配置管理中的作用,以期为同行提供经验参考。方法回顾2023年1—11月我院Ⅱ期、Ⅲ期抗肿瘤药物临床试验中的冲配工作,总结GCP药师参与Ⅱ期、Ⅲ期临床试验产生的积极作用。结果2023年1—11月的所有在研临床试验配置工作显示:①冲配临床试验药物4464袋,没有发生因冲配错误导致用药延迟的事件;②GCP药师拦截次数共19次,主要涉及药物剂量错误、冲配表单不规范等;③共发生不良反应事件314次,其中III度、IV度不良事件83次,发生次数最多的不良反应主要有眼科毒性、中性粒细胞数降低、血小板数降低及白细胞数降低等,涉及的药物主要有抗体偶联药物、紫杉醇、顺铂等;④GCP药师不断优化工作流程,制定相关SOP及标准化配置表单。结论GCP药师参与抗肿瘤药物临床试验配置管理,在方案审核、药物配置规范执行、人员防护、不良反应监测等各环节都能发挥积极的作用。同时他们可以极大地提高配置效率,有效保证输液质量,保障抗肿瘤药物临床试验用药安全。

II期临床试验设计方案及其C++编程

II期临床试验通常用于新的治疗方法疗效的初步评估.传统的二阶段设计只考虑总的响应这一个解释变量.陆盈等人提出了一种新的试验方案,同时考察总的响应和完全响应两个变量,他们的试验设计为II期临床试验提供了更多更好的选择.但是相应的计算程序是用S-P lus编写的,运行时间过长.改用C++编程,制作的软件计算速度相对较快,而且在W indows环境下就可运行,这将方便广大医学工作者临床使用.

Efficacy and toxicity of capecitabine combined with intensitymodulated radiotherapy after D1/D2 lymph node dissection in patients with gastric cancer

BACKGROUND Adjuvant chemoradiotherapy(ACRT)with oral capecitabine and intensitymodulated radiotherapy(IMRT)were well tolerated in a phase I study in patients who had undergone partial or total gastrectomy for locally advanced gastric cancer(GC).This phase II study aimed to further determine the efficacy and toxicity of this combination after radical resection and D1/D2 lymph node dissection(LND)for patients with locally advanced GC.AIM To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced GC.METHODS Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this study.The patients received ACRT comprising IMRT(total irradiation dose:45 Gy delivered in daily 1.8-Gy fractions on 5 d a week over 5 wk)and capecitabine chemotherapy(dose:800 mg/m²twice daily throughout the duration of radiotherapy).The primary study endpoint was disease-free survival(DFS),and the secondary endpoints were overall survival(OS),toxic effects,and treatment compliance.RESULTS The 3-year DFS and OS were 66.2%and 75%,respectively.The median time to recurrence was 19.5 mo(range,6.1-68 mo).Peritoneal implantation(n=10)was the most common recurrence pattern,and the lung was the most common site of extra-abdominal metastases(n=5).Nine patients developed grade 3 or 4 toxicities during ACRT.Two patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of capecitabine.There were no treatmentrelated deaths.CONCLUSION The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.

Sequential versus simultaneous use of vinorelbine and capecitabine at the same dosage as first-line chemotherapy for patients with metastatic breast cancer

Objective:It remains unclear whether simultaneous use of two chemotherapeutic drugs is better than sequential use.This trial was designed to explore efficacy and safety of sequential vs simultaneous use of vinorelbine and capecitabine at the same dosage as first-line therapy in metastatic breast cancer (MBC).Methods:This was a un-icenter, randomized phase II trial.Patients randomized into the simultaneous group (group A) were simultaneously administered with vinorelbine and capecitabine while those in the sequential group (group B) received vinorelbine followed by capecitabine at the same dosage.Results:Sixty-six patients were screened and 30 patients were randomized into either group.There're significant differences in the clinical benefit rate (CBR) with 80.0% for group A vs 53.3% for group B (P=0.028).With a median follow up time of 13.5 months, there were no significant differences between the two groups in PFS (median PFS:7.70 months for group A vs 7.23 months for group B, P=0.436).Grade III or IV neutropenia (83.3% vs 50.0%, P=0.006), all grades of fatigue (56.7% vs 30.0%, P=0.037) and anorexia (53.3% vs 23.3%, P=0.017) were significantly more frequent in simultaneous group.Conclusion:Simultaneous administration of vinorelbine and capecitabine can bring about improvements in CBR, but cannot translate into long-term benefits, such as progression-free survival (PFS) or overall survival (OS).These findings, combined with a relatively better tolerability in sequential group, showed that both simultaneous and sequential administrations are reasonable options for MBC patients.

Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study

Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.

枳术宽中胶囊治疗功能性消化不良403例的Ⅱ期临床试验

目的 :观察枳术宽中胶囊治疗功能性消化不良 (FD )的疗效及安全性。方法 :采用双盲双模拟对照方法 ,将 4 0 3例FD病人随机分为治疗组(196例 ) ,给枳术宽中胶囊 3粒 ,po ,tid ,同时给西沙必利模拟片B ;对照组 (10 5例 ) ,给西沙必利 5mg ,po ,tid ,同时给枳术宽中模拟胶囊A ;开放组 (10 2例 ) ,给枳术宽中胶囊 3粒 ,po ,tid。 2wk为一个疗程。结果 :治疗组、对照组对中医证候的总有效率分别为 86 .7% ,77.1% (P >0 .0 5 )。开放组对中医证候的总有效率为 89.2 %。服药后治疗组与对照组胃排空的比较 ,差异无显著性 ,未发现治疗组有明显不良反应。结论 :枳术宽中胶囊治疗功能性消化不良安全有效。

重组人粒细胞集落刺激因子预防化疗后粒细胞减少的Ⅱ期临床试验

目的：评价重组人粒细胞集落刺激因子（ｒｈＧ－ＣＳＦ）对预防恶性肿瘤化疗后粒细胞减少的作用及不良反应。方法：６２例恶性肿瘤病人随机分入ＡＢ和ＢＡ２组。Ａ为治疗周期，即化疗结束４８ｈ开始，ｒｈＧ＿ＣＳＦ５μｇ／ｋｇ，ｓｃ，ｑｄ×７～１５ｄ；Ｂ为空白对照周期。自化疗开始隔日查血常规１次，观察中性粒细胞（Ｎｅｕ）绝对值及白细胞（ＷＢＣ）的变化。结果：治疗周期于ｒｈＧ＿ＣＳＦ注射２４ｈ后，ＷＢＣ及Ｎｅｕ绝对值迅速上升，４８ｈ出现第１个高峰，ｄ８出现第２个高峰，而对照周期化疗后ＷＢＣ和Ｎｅｕ绝对值逐渐下降，始终低于治疗周期。ＷＢＣ和Ｎｅｕ的最低值（ＷＢＣ＜４．０×１０９／Ｌ，Ｎｅｕ绝对值＜２．０×１０９／Ｌ）的持续时间，以及化疗后ｄ２１ＷＢＣ＜４．０×１０９／Ｌ的病例数在治疗周期和对照周期间差异有显著意义（Ｐ＜０．０５）。骨痛和感冒症状发生率分别为２１％和１６％，注射部位局部反应、皮疹、发热少见。结论：ｒｈＧ＿ＣＳＦ可以促进化疗病人ＷＢＣ和Ｎｅｕ的恢复，耐受性良好，可以作为肿瘤化疗中提高剂量强度的有效的辅助药。

中断研发的头孢菌素类抗生素

头孢菌素研发以来,新药不断开发上市的同时,许多候选物经历了筛选淘汰的过程,但它们却有存在的价值。本文对中断研发的头孢菌素类抗生素做一简要综述,特别是Ⅲ期临床中断研发的6个候选物和Ⅱ期临床中断研发的5个候选物。

甲磺酸酚妥拉明片/胶囊治疗阴茎勃起功能障碍的临床研究

目的 :为了解甲磺酸酚妥拉明在治疗阴茎勃起功能障碍 ( ED)中的有效性和安全性。方法 :采用随机安慰剂对照试验研究的方法进行分析。试验分为片剂组 ( A组 )、胶囊组 ( B组 )、安慰剂的片剂和胶囊组并为一组 ( C组 )。组间比例为 1∶ 1∶ 1 ( A∶B∶C)。共有 2 41例参加了临床试验 ,其中 2 1 7例完成试验。试验药物 (片剂或胶囊 )必须在性交前 1h服用 ,每次服 1片 ( 4 0 mg) ;两周内至少有 3次服药并尝试性交以保证达到统计学要求 ,但服药不能超过 8次 ;整个试验持续 1 0周。药物的有效性按国际性功能量表 ( IIEF)衡量 ,安全性以监测试验过程中的不良反应来反映。结果 :有效率 ,A组为 6 8% ,B组为 6 2 % ,C组为 45%。 A、B组和 C组比效有显著性差异。整个试验未发生严重不良反应。结论

司美替尼联合多西紫杉醇治疗KRAS突变阳性晚期非小细胞肺癌的疗效

1文献来源 Janne PA, Shaw AT, Pereira JR, et al. Selumetinib plus Docetaxel for KRAS-mutant advanced non-small-cell lung cancer： A randomised, multicentre, placebo-controlled, phase 2 study [J].