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.

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.

Unit 1 of Ling’ao Nuclear Power Plant phase II underwent hot functional test successfully

On February 25, the Unit 1 of Ling’ao Nuclear Power Plant phase II underwent a 41-day-long hot functional test successfully with its major systems satisfying the requirements for

Supply contract for Nantong Power Plant Phase II signed

Power generating equipment supply contract for Huaneng Nantong Power Plant Phase Ⅱ project affiliated to Huaneng International Electric Power Stock Company Ltd. was signed at the People’s Great Hall on June 28, 1996, Shi Dazhen, Minister of Electric Power, Ye Qing, Vice-chairman of the State Planning Commission, Zhang Youcai, Vice Minister of Finance and

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 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 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 Erlotinib in Patients with Previously Treated Non-Small Cell Lung Cancer

Background: Erlotinib has been reported to be effective for the treatment of non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of erlotinib under conditions similar to daily clinical practice, a phase II trial was conducted in Japanese patients with previously treated NSCLC. Methods: The eligibility criteria were stage IIIB/IV NSCLC, a performance status (PS) of 0 - 2, and previous treatment with 1 - 2 non-EGFR-TKI regimens. Patients received erlotinib (150 mg/day) orally until disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR). In addition, the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and EGFR gene mutation status were evaluated. Results: Thirty-eight patients were enrolled, and 37 patients were evaluated. The median age was 69 years (range, 50 - 80 years). Patient characteristics were as follows: 26 were male and 11 were female;12 had a PS of 0, 20 had a PS of 1, and 5 had a PS of 2;and 26 had adenocarcinoma, and 11 had non-adenocarcinoma histology. The ORR and DCR were 21.6% (95% confidence interval [CI], 11.4% - 37.2%) and 54.1% (95% CI, 35.9% - 66.6%), respectively. Twenty-seven patients could be evaluated for EGFR gene status (12, mutated;15, wild-type). The ORR for EGFR-mutated patients was 41.7%, while that for patients with wild-type EGFR was 13.3%. The median PFS was evaluated as 4.4 months (95% CI, 2.2 - 10.7 months). The median OS was 14.9 months (95% CI, 9.2 months - not reached). Common adverse events were tolerable skin toxicities, diarrhea, and stomatitis. In addition, interstitial lung disease occurred in 8.1% of patients. Conclusion: As efficacy and safety were similar to previous studies, erlotinib was found to be effective for Japanese patients with previously treated NSCLC in clinical practice.

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.

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.

Phenotype prediction of nonsynonymous single nucleotide polymorphisms in human phase II drug/xenobiotic metabolizing enzymes: perspectives on molecular evolution

Nonsynonymous single nucleotide polymorphisms (nsSNPs) in coding regions can lead to amino acid changes that might alter the protein’s function and account for susceptibility to disease and altered drug/xenobiotic response. Many nsSNPs have been found in genes encoding human phase II metabolizing enzymes; however, there is little known about the relationship between the genotype and phenotype of nsSNPs in these enzymes. We have identified 923 validated nsSNPs in 104 human phase II enzyme genes from the Ensembl genome database and the NCBI SNP database. Using PolyPhen, Panther, and SNAP algorithms, 44%?59% of nsSNPs in phase II enzyme genes were predicted to have functional impacts on protein function. Predictions largely agree with the available experimental annotations. 68% of deleterious nsSNPs were correctly predicted as damaging. This study also identified many amino acids that are likely to be functionally critical, but have not yet been studied experimentally. There was significant concordance between the predicted results of Panther and PolyPhen, and between SNAP non-neutral predictions and PolyPhen scores. Evolutionarily non-neutral (destabilizing) amino acid substitutions are thought to be the pathogenetic basis for the alteration of phase II enzyme activity and to be associated with disease susceptibility and drug/xenobiotic toxicity. Furthermore, the molecular evolutionary patterns of phase II enzymes were characterized with regards to the predicted deleterious nsSNPs.

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).

Tuning Reaction Processes for the Synthesis of Micron and Nanometer Sized, Single Crystalline Lamellae of Copper 7,7,8,8-tetracyano-p-quinodimethane (Phase II) with Large Area

Two simple methods have been demonstrated to obtain large area,single crystalline lamellae of copper-7,7,8,8-tetracyanoquinodimethane(CuTCNQ).The formation of the lamellae was a result of fine tuning of the processes during the synthesis processes of CuTCNQ phase II.This facile synthesis of large area single crystalline lamellae suggests bright prospects for the study and understanding of the electrical switching of CuTCNQ by using single crystals of its phase II,and future applications of the material in memory and switching devices.

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.

Single-arm phase II three-outcome designs with handling of over-running/under-running

Phase II clinical trials are commonly conducted as pilot studies to evaluate the efficacy and safety of the investigational drug in the targeted patient population with the disease or condition to be treated or prevented.When designing such a trial considering efficacy conclusions,people natu-rally think as follows:if efficacy evidence is very strong,a go decision should be made;if efficacy evidence is very weak,a no-go decision should be made;if the efficacy evidence is neither strong nor weak,no decision can be made(inconclusive).The designs presented in this paper match this natural thinking process with go/no-go/inconclusive outcomes.Both two-/three-stage designs are developed with three outcomes.Additionally,a general approach based on conditional error function is implemented such that new decision boundaries can be calculated to handle mid-course sample size change which results in either‘over-running’or‘under-running’and ensure the control of overall type I error.A free open-source R package tsdf that calculates the proposed two-/three-stage designs is available on CRAN.

Surface Modification of PEEK-WC Membranes by Wet Phase Inversion for Ni(II) Adsorption

This work focuses on the preparation and characterization of flat sheet membrane based on modified polyether ether keetone (PEEK-WC). Additives, such as dibutyl phatalate (DBP) and diethyl hexyl phosphoric acid (DEHPA), were used to investigate their effect on membranes properties which are prepared by immersion precipitation. For that, several techniques were used to characterize membranes like thermal analyses, scanning electron microscopy and microanalyses. SEM pictures show versatile structures of the membranes from dense to porous membranes characterized by a sponge and finger like structure. Moreover, microanalyses of both surfaces, bottom and top surfaces show an aggregation of DEHPA at the top surface of the membrane. However, by adding dibutylphtalate, a well dispersion of the extractant was observed. Initially, micro-porous membranes were used in supported liquid membranes experiments for Ni(II) metal ions transports using diethyl hexyl phosphoric acid (DEHPA) as carrier. The extraction efficiency was very low about 28%, but enhanced by adding xylene to the organic phase. However, the modified membranes (with additives) by DBP and DEHPA were used on solid liquid extraction of Ni(II). The results show that by adding the plasticizer and the extractant, the efficiency of the system reached 63%.

18α-甘草酸二铵对大鼠肝脏细胞色素P450和II相酶的影响

目的 研究 18α 甘草酸二铵 (18α GL)对肝脏药物代谢酶的影响。方法 ♂Wistar大鼠ig 18α GL 12 5和 5 0mg·kg-1,分别给药 3 ,6和 12d ,对照组给等容量的溶媒。酶学测定肝微粒体细胞色素P45 0 (CYP) ,尿苷二磷酸葡萄糖醛酸转移酶 (GT)和谷胱甘肽巯基转移酶 (GST)活性。结果 18α GL抑制苯胺羟化酶 ,乙氧异唑脱乙基酶和红霉素脱甲基酶活性 ,抑制率分别可达 5 3 2 % ,47 3%和 34 3 % ;增加GT1(底物为 7 甲基 4 羟基 香豆素 ) ,GT2 (底物为 4 羟基联苯 )和GST活性 ,分别可达 2 9 9% ,70 3%和 48 3 %。结论 18α GL对大鼠肝微粒体I相酶(CYP2E1,CYP1A1和CYP3A)主要是抑制作用 ,对II相酶 (GT1,GT2 和GST)

国产奈达铂治疗恶性肿瘤II期临床研究

目的 观察国产奈达铂单药及联合其他化疗药物治疗非小细胞肺癌、食管癌、鼻咽癌的疗效及不良反应。方法 单盲随机对照II期临床研究。入组共 4 3例 ,单药组 4例 ,联合化疗组 39例 (治疗组2 1例 ,对照组 18例 )。奈达铂 80～ 10 0mg/m2 ,加入 5 0 0ml生理盐水中静滴 2小时 ,每 3～ 4周重复。结果 入组 4 3例 ,能评价疗效的 4 2例。非小细胞肺癌治疗组 13例 ,PR 3例 ,有效率 2 3% ;对照组 12例 ,PR 3例 ,有效率 2 5 % ,二组无差异。食管癌治疗组 6例 ,PR 2例 ,有效率 33.3% ;对照组 5例 ,PR 1例 ,有效率 2 0 %。鼻咽癌治疗组 1例达SD ,对照组 1例达PR。非小细胞肺癌单药 4例 ,疗效均为SD。毒副反应单药组轻微 ,联合化疗组二组相似 ,但治疗组无肾功能毒性。结论 奈达铂对非小细胞肺癌、食管癌有一定疗效 ,在非小细胞肺癌疗效与顺铂相近 ,在食管癌中疗效优于顺铂 ,且无肾毒性。

LC/DAD/MSD技术研究大鼠胆汁中盐酸非洛普的II相代谢产物

目的 研究大鼠服药后胆汁中盐酸非洛普 (DDPH)II相代谢产物。方法 收集大鼠空白胆汁及给药后12h内的胆汁 ,以LC/DAD/MSD技术判断II相代谢产物峰位。以HPLC法制备II相代谢产物馏分并以 β 葡糖醛酸酶水解 ,再进行分析 ;同时将与II相代谢产物相应的I相代谢产物对照品按相同条件进行分析对照。结果 大鼠给药后胆汁色谱图中峰M7,M8和M9为DDPH的II相代谢产物 ,它们的 β 葡糖醛酸酶水解产物分别为M3,M2 和M1。结论 β 1 O {3 ,5 二甲基 4 [ 2 甲基 2 ( 3 ,4 二甲氧基苯乙氨基 ) 乙氧基 ] 苯基 } 葡糖醛酸 (M7) ,β 1 O {2 ,4 二甲基 3 [2 甲基 2 ( 3 ,4 二甲氧基苯乙氨基 ) 乙氧基 ] 苯基 } 葡糖醛酸 (M8)和 β 1 O {2 甲氧基 4 [1 甲基 2 ( 2 ,6 二甲基苯氧基 ) 乙氨基 乙基 ] 苯基 } 葡糖醛酸 (M9)

CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase Ⅱ trial

Objective： The aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy（NAC） using oxaliplatin plus capecitabine（Cap OX） for patients with operable locally advanced colon cancer（CC）.Methods： Patients with computed tomography-defined T4 or lymph node-positive CCs were enrolled. After radiological staging, patients were treated with at least 2 cycles of NAC consisting of 130 mg/m2 oxaliplatin on d 1,plus 1,000 mg/m2 capecitabine twice daily for 14 d every 3 weeks, followed by surgery, and then with the rest cycles of adjuvant chemotherapy. Radiological response was evaluated after 2 cycles of NAC. Tumor response, treatment toxicity, and surgical complications were recorded. The pathological response to therapy was evaluated according to the tumor regression grade（TRG） score. The primary endpoint was pathologic tumor response. This trial is registered in Clinical Trials.gov（No： NCT02415829）.Results： Forty-seven patients were enrolled in the study. Forty-two patients completed the planned treatments.The total radiological response rate was 68%（32/47）, including complete and partial response rates of 2%（1/47）and 66%（31/47）, respectively. Stable disease was observed in 32%（15/47） and progressive disease was observed in none. Complete pathologic response, major regression, and at least moderate regression were achieved in 1（2%）, 2（4%）, and 29（62%） patients, respectively. Four patients developed grade 3 treatment toxicities. One patient with wound infection occurred after operation（1/47, 2%）. There was no treatment-related death.Conclusions： Our results suggest that NAC with Cap OX is an effective and safe treatment option for patients with locally advanced CCs.