Safety and clinical responses in ankylosing spondylitis after three months of etanercept therapy

We aimed to evaluate the safety and clinical responses in Korean ankylosing spondylitis (AS) patients after three months of etanercept therapy. AS patients satisfying the Modified New York Criteria were enrolled. They were assessed for safety and clinical responses at enrollment and after three months of etanercept therapy. A total of 124 patients completed the study. After three months, the rate of ASsessment in AS International Working Group 20% improvement (ASAS 20) response was 79.8%. The rates of ASAS 40 and ASAS 5/6 responses were 58.5 and 62.8%, respectively. Significant improvement of Korean version of Bath AS Disease Activity Index (KBASDAI) (p<0.0001), Bath AS Functional Activity Index (BASFI) (p<0.0001), and Bath AS Metrology Index (BASMI) (p=0.0009) were achieved after three months. Quality of life was also significantly improved after three months, as demonstrated by scores for SF-36 (p<0.0001) and EQ-5D (p<0.0001). Erythrocyte sedimentation rate and C-reactive protein were significantly decreased (p<0.0001, p<0.0001, respectively). None of the patients developed tuberculosis and there were no serious adverse event. AS patients with inadequate response to conventional therapy showed significant clinical improvement without serious adverse events after three months of etanercept therapy.     

Efficacy and Safety of Anti-Tumour Necrosis Factor in Elderly Patients with Rheumatoid Arthritis: An Observational Study

This study aims to compare the efficacy and safety of anti-TNF agents in elderly (aged ≥65 years) and younger patients (aged 18–65 years) with active RA. The study involved 1,114 RA patients treated with anti-TNF drugs and followed-up for >6 months by LORHEN group, who were divided into two cohorts on the basis of their age (311 aged ≥65 and 803 aged <65 years) in order to evaluate 3-year outcomes and treatment discontinuations. Drug effectiveness was assessed by disease activity (DAS28 and EULAR response), functional status (HAQ) and serological parameters (ESR) at baseline and during anti-TNFα therapy; safety was evaluated on the basis of drug discontinuation rates. At baseline, the elderly patients showed greater disease activity (DAS28, ESR) and loss of joint function (HAQ, functional class; p?<?0.05). During therapy, clinical and laboratory parameters (DAS28, ESR) improved in both groups without any statistically significant difference between them, whereas the difference in HAQ remained after 36 months of treatment (p?<?0.05). Anti-TNFα therapy was discontinued by 123 of the elderly (42%) and 282 of the younger patients (36.6%) because of loss of efficacy (17.4% vs. 16.7%), severe adverse events (21.8% vs. 16.9%) or other reasons (2.7% vs. 3%). The number of adverse events was significantly higher in the elderly patients (p?<?0.05). Anti-TNFα treatment reduced disease activity and led to functional improvement in both groups, although the baseline difference in HAQ remained statistically significant at the end of the follow-up. The elderly patients experienced more infective events.     

Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT) after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT) maintenance therapy. We compared time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45); the median TTP (MTTP) for the complete treatment was 9.43 months (95%CI=8.38-10.48 months) for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004) for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months) for the CMT group and 2.0 months (95%CI=1.63-2.38 months) for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile.     

Short communication: the efficacy of fixed dose rate infusion of gemcitabine combined with IFN-alpha2a in patients with advanced refractory renal cell carcinoma.

The fixed dose rate (FDR) infusion of gemcitabine is based on pharmacokinetic studies demonstrating an increased peak concentration of gemcitabine-active metabolites inside the cell. In this prospective study, for the first time we investigated gemcitabine FDR infusion together with interferon-alpha2a (IFN-alpha) in pretreated patients with advanced renal cell carcinoma (RCC). Twelve patients received 800 mg/m2 gemcitabine (i.v. infusion of 10 mg/m2/min) on days 1 and 8 every 3 weeks, combined with 3.0 x 10(6) U s.c. IFN-alpha on days 1, 3, and 5 of each week. Median age of patients was 64 years, and the Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1 in 10 patients. All patients were pretreated, 5 with > or =2 lines of chemoimmunotherapy. A median number of five cycles of gemcitabine per patient were given, with a mean weekly dose intensity of 72% of that planned. Among 11 evaluable patients, 2 (18%) partial responses and 5 (46%) stable diseases (median duration of 9.3 months) were observed. Median time to progression (TTP) and overall survival were 7.1 months and 13.0 months, respectively. The most frequently occurring grade 3 or 4 adverse events were leukoneutropenia (25%), thrombocytopenia (17%), and diffuse edema (25%). One patient developed a cerebrovascular accident potentially related to treatment. These promising results with the combination of gemcitabine infused at FDR and IFN-alpha deserve further investigation.     

Capecitabine and vinorelbine in patients with metastatic breast cancer previously treated with anthracycline and taxane

We have evaluated the efficacy and safety of the combination of capecitabine and vinorelbine in metastatic breast cancer (MBC) patients previously treated with anthracycline-and taxane-containing regimens. Between April 2000 and September 2002, 44 female MBC patients received oral capecitabine (1,250 mg/m2 twice daily on days 114), and intravenous vinorelbine (25 mg/m2 on days 1 and 8) during each 3 week-chemotherapy cycle (median, 5 cycles/patient; total, 235 cycles). One patient achieved a complete response and 21 patients had partial responses, giving an overall response rate of 50% in the intention-to-treat analysis (95% CI, 35.0-65.0%). Median duration of response was 6.0 months (range 1.2-23.0 months). Patients were followed- up for a median of 16 months, with median progression-free survival being 5.3 months, and median overall survival being 17 months. Toxicities included grades III and IV neutropenia in 63 (26.8%) and 4 (1.7%) cycles, respectively, and grades II and III hand-foot syndrome in 12 (5.1%) and 4 (1.7%) cycles, respectively. Other nonhematologic toxicities were minimal and manageable. In conclusion, the combination of capecitabine and vinorelbine was effective and well tolerated in MBC patients even after treatment with anthracyclines and taxanes.     

单药替吉奥胶囊治疗老年晚期胃癌的临床观察

目的：观察单药替吉奥胶囊治疗晚期胃癌的临床疗效及毒副反应。方法：选择50例经病理证实的老年晚期胃癌患者,随机分为治疗组32例及对照组18例。治疗组根据体表面积给予替吉奥胶囊治疗,对照组给予营养等最佳支持治疗。每2周期后行影像学检查评价疗效、记录不良反应及随访情况。结果：治疗组32例患者CR(完全缓解)0例,PR(部分缓解)10例,SD(病情稳定)12例,PD(病情进展)10例,临床总缓解率31.3%,临床获益率68.8%。治疗组中位无疾病进展时间及中位生存期分别为5.7及11.5个月,对照组分别为3.1及7.6个月。毒副反应主要为I-III度骨髓抑制、消化道反应、肝功能损伤及手足综合症。结论：单药替吉奥胶囊治疗老年晚期胃癌效果肯定,生活质量高、毒副作用小。     

Weekly Paclitaxel and Trastuzumab as a First-Line Therapy in Patients with HER2-Overexpressing Metastatic Breast Cancer: Magnitude of HER2/neu Amplification as a Predictive Factor for Efficacy

We evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab as firs-tline chemotherapy in women with HER2-overexpressing metastatic breast cancer (MBC), and we investigated the prognostic factors including magnitude of HER2/neu amplification in this population. We analyzed 54 patients with HER2-overexpressing MBC that were treated with weekly paclitaxel plus trastuzumab as first-line chemotherapy from February 2004 to December 2006. At a median follow-up of 28 months, median time to progression (TTP) was 16.6 months (95% CI, 9.4 to 23.7 months) and median overall survival was 25.6 months (95% CI, 21.8 to 27.3 months). Therapy was generally well tolerated, although three patients (5.5%) experienced reversible, symptomatic heart failure. Of the 27 patients evaluable for the HER2 FISH, patients with a HER2/CEP17 ratio of ≤4.0 had significantly shorter TTP than those with a HER2/CEP17 ratio of >4.0 (10.8 vs. 23.2 months, P=0.034). A HER2/CEP17 ratio of >4.0 was identified as significant predictive factor of TTP by multivariate analysis (P=0.032). The combination of weekly paclitaxel plus trastuzumab as first-line chemotherapy is an effective regimen in patients with HER2-FISH-positive MBC. Furthermore, the magnitude of HER2 amplification is an independent predictive factor of TTP.     

Trastuzumab

black triangle Trastuzumab is a recombinant humanised monoclonal antibody specific for the growth factor receptor p185(HER2) (HER2) which is overexpressed in 25 to 30% of breast cancer tumours. black triangle The drug inhibits the growth of human breast cancer cells overexpressing HER2 in vitro and in vivo. It shows additive antitumour activity in vitro and in vivo when administered with paclitaxel, doxorubicin, various cytokines or tamoxifen. black triangle In patients with metastatic breast cancer whose tumours overexpressed HER2, trastuzumab (4 mg/kg loading dose then 2 mg/kg/week by intravenous infusion) produced objective responses in 21% of 213 patients. A further 7% of patients had minor responses and 30% had stable disease. black triangle Combination therapy with trastuzumab and either paclitaxel or doxorubicin (or epirubicin) plus cyclophosphamide produced a higher response rate (49%), longer median time to disease progression (7.6 months), a higher one-year survival rate (78%) and significantly increased median overall survival (25.4 months) than antineoplastic agents alone (response rate 32%, time to disease progression 4.6 months, one-year survival rate 67% and overall survival 20.3 months) in a phase III study in 469 patients. black triangle Trastuzumab is generally well tolerated. Chills, fever, nausea, vomiting, weakness and headache were among the most common adverse events in clinical trials and occurred in 40 to 50% of patients during the first infusion of the drug. Cardiac dysfunction was the most serious adverse event reported and was more common in patients receiving trastuzumab plus antineoplastic therapy than in those receiving trastuzumab alone.     

Clinical Efficacy of a 24-months Course of Lamivudine Therapy in Patients with HBeAg Negative Chronic Hepatitis B: A Long-term Prospective Study

The optimal duration of oral nucleos(t)ide analogue therapy for HBeAg negative chronic hepatitis B (CHB) has not been defined. The aim of this study was to investigate the clinical efficacy of 24-months course of lamivudine therapy in patients with HBeAg negative CHB in Korea. A total of 50 Korean patients with HBeAg negative CHB were prospectively enrolled. The patients received 100 mg/day of lamivudine orally for 24 months. Patients who showed complete response at 24 months to lamivudine therapy stopped treatment, and regular follow-up was done thereafter. The mean follow-up duration after cessation of therapy was 40.8±22.7 (range 12-96) months. The complete response rate at months 12 and 24 were 86.0% (43/50) and 86.0% (43/50), respectively, and the clinical breakthrough at months 12 and 24 were 4.0% (2/50) and 14.0% (7/50), respectively. The expected durability of responses at months 12, 24, and 36 after cessation of lamivudine therapy in 43 complete responders was 79.1%, 64.0%, and 56.9%, respectively. In conclusion, a 24-months course of lamivudine therapy shows high end-treatment response rate and substantial durability of initial response after cessation of therapy in HBeAg negative CHB patients in Korea.     

Highly effective peginterferon α-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea

Background/Aims

Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon α-2a plus ribavirin for CHC in hemophilia.

Methods

Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests.

Results

Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naïve patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis.

Conclusions

Peginterferon α-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.     

Efficacy and safety of caspofungin therapy in elderly patients with proven or suspected invasive fungal infections

Invasive fungal infections (IFIs) are serious complications in elderly adults. Caspofungin may provide a useful therapeutic option for elderly patients with or at high risk for IFIs. We retrospectively compared efficacy and safety outcomes in elderly (>/=65 years of age) and non-elderly patients in three clinical trials of caspofungin: a double-blind, randomized trial versus amphotericin B for documented invasive candidiasis (IC); an open-label, non-comparative study of definite or probable invasive aspergillosis (IA); and a double-blind, randomized trial versus liposomal amphotericin B as empirical therapy (ET) in febrile neutropenic patients. A total of 159 elderly patients with a median age of 71 years (range, 65-84) received caspofungin in these studies. The median duration of caspofungin therapy was 12 days for IC and ET, and 28 days for IA. Point estimates for the favorable response rates to caspofungin were numerically higher in elderly versus non-elderly patients with IC (83% vs. 68%) or IA (64% vs. 44%) and were similar in patients receiving ET (36% vs. 34%). Adverse events related to caspofungin occurred in generally similar proportions of elderly versus non-elderly patients with IC (clinical, 33% vs. 27%; laboratory, 17% vs. 29%), with IA (clinical, 7% vs. 13%; laboratory, 13% vs. 14%), or receiving ET (clinical, 47% vs. 47%; laboratory, 24% vs. 22%). Nephrotoxicity and infusion-related toxicity developed in comparable proportions of elderly and non-elderly caspofungin recipients in all three studies. In this post-hoc analysis, caspofungin appeared to be as efficacious and well tolerated in elderly patients as in non-elderly patients.     

Advances in anti-inflammatory therapy

Our goal was to evaluate the state of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA), before the introduction of the coxibs. The prerequisite for inclusion was the presence of RA (ACR criteria) plus therapy with an NSAID with or without a disease modifying antirheumatic drug (DMARD). A total of 368 consecutive RA patients (81% women) from the outpatient clinic at the Vienna General Hospital were included. Rheumatoid factor was positive in 62%, the patients' mean age was 60 +/- 14 years. The period of observation was 1972-1998. Seventy-seven per cent of the patients had DMARD and NSAID therapy. NSAID therapy was dominated by diclofenac, accounting for 60% of all therapies. Eighteen other substances were applied more rarely. All NSAIDs together were given for 768 patient years (with a mean duration of therapy of 17 years +/- 21 months). Seventy-two per cent of the patients received GI-protective therapy mainly with histamine antagonists and sucralfate while on nonsteroidal therapy. NSAID toxicity mostly affected the GI tract. There was a similar incidence of GI-related adverse events between patients with and patients without GI protection, mainly dyspepsia and nausea. NSAIDs have the potential to cause adverse events in the GI tract. Therapy with histamine antagonists or sucralfate did not reduce the patients' rate of gastrointestinal adverse events.     

A Phase 3 Randomized Study of Remestemcel-L versus Placebo Added to Second-Line Therapy in Patients with Steroid-Refractory Acute Graft-versus-Host Disease

Uncontrolled studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be effective against acute graft-versus-host disease (aGVHD). We conducted a multicenter, randomized study to assess the efficacy of using ex vivo cultured adult human MSC (remestemcel-L) in addition to second-line therapy to treat steroid-refractory aGVHD (NCT00366145). In total, 260 patients, 6 months to 70 years of age, were enrolled from August 2006 to May 2009 and were randomized 2:1 to receive 8 intravenous infusions of remestemcel-L or placebo, given over 4 weeks, in addition to second-line therapy according to institutional standards. Four additional infusions over 4 weeks were indicated for patients with incomplete response at day 28. Randomization was stratified by aGVHD grade. Efficacy and safety were assessed through 180 days of follow-up, with the primary endpoint being durable complete response (DCR), defined as complete resolution of aGVHD symptoms for any period of at least 28 days after beginning treatment. Remestemcel-L did not meet the primary endpoint of greater DCR in the intent-to-treat population (35% versus 30%; P = 0.42). In post hoc analyses, patients with liver involvement who received at least 1 infusion of remestemcel-L had a higher DCR, and higher overall complete or partial response rate (OR) than those who received placebo (29% versus 5%; P = .047). Among high-risk patients (aGVHD grades C and D), remestemcel-L demonstrated significantly higher OR at day 28 than placebo (58% versus 37%; P = 0.03). Furthermore, pediatric patients had a higher OR with MSCs compared with placebo (64% versus 23%; P = .05). Similar rates of adverse events were observed between treatment groups. Remestemcel-L was safe and well tolerated. Results of this study did not demonstrate superior DCR compared with placebo when added to standard of care. The favorable clinical responses seen in some patient subsets may warrant further investigation.     

替吉奥胶囊在晚期大肠癌患者维持治疗中的临床观察

目的：观察替吉奥在晚期大肠癌(结直肠癌)患者维持治疗的疗效和不良反应。方法：38例确诊为晚期大肠癌的患者,经过氟尿嘧啶类组成的联合化疗方案化疗4~6周期,化疗后部分缓解(partial response,PR)或疾病稳定(stable disease,SD)的患者,被分为治疗组和观察组。治疗组采用替吉奥单药口服维持治疗,连用2周,停药1周,3周为一个周期。观察组不予任何治疗。每2周期后行影像学检查评价疗效、不良反应及随访情况。结果：治疗组总有效率为45.5%,临床受益率为81.8%,中位无疾病进展时间为5.7个月,中位总生存期为10.9个月;观察组总有效率为31.3%,临床受益率为68.8%,中位无疾病进展时间为3.1个月,中位总生存期为6.7个月;两组近期疗效、中位无疾病进展时间及中位生存期比较差异有统计学意义(P<0.05)。毒副反应主要为Ⅰ~Ⅲ度骨髓抑制、消化道反应、肝功能损伤及手足综合症。结论：替吉奥在晚期大肠癌患者维持治疗中效果肯定、生存质量高、毒副作用小。     

紫杉醇顺铂方案联合自体CIK细胞输注治疗晚期食道癌的临床分析

目的:晚期食道癌的的治疗以化疗为主,紫杉醇顺铂方案治疗晚期食道癌因疗效确定,在临床应用日益推广。自体CIK细胞治疗晚期恶性肿瘤能起到延缓或阻止肿瘤的转移与复发,并可提高晚期食道癌患者的细胞免疫功能及改善生活质量等综合作用。本组应用紫杉醇顺铂方案联合自体CIK细胞输注治疗晚期食道癌患者,旨在探讨采用自体CIK细胞输注同步化疗的综合治疗方法,是否能提高晚期食道癌的临床疗效。方法:本科自2008年1月至2010年1月共入选59例患者。均为Ⅳ期食道癌病人。化疗方案剂量及方法设定:自体CIK治疗操作流程:采血前一天需对患者进行血常规检测,对于白细胞数低于8×109L-1的患者应于采血前24小时注射1～2支集落刺激因子。采血前急查血常规,确认患者白细胞数达到或高于8×109L-1时方可采血,采集患者静脉血50 ml。培养至14天左右细胞成熟,经检验科和实验室测量CIK细胞数量达1×109～11L-1时,对细胞培养物进行无菌检测,当检验科和实验室自身均检测无菌后,安排进行回输。自体CIK细胞输注+紫杉醇顺铂方案治疗组:Cik采血,d1,紫杉醇PTX 175 mg/m2,d2,顺铂DDP 20 mg/m2,静滴d3-7,紫杉醇使用前严格按照说明书进行预处理。CIK回输:d14。21天为1个周期,2个周期后评价疗效。结果:全组59例患者总有效率为32.2%(19/59),其中完全缓解率为1.7%(1/59),部分缓解率为30.5%(18/59),稳定52.5%(31/59),进展15.2%(9/59)。中位进展时间7.6个月,中位生存时间11.7个月。主要毒性反应为外周血细胞下降、脱发及外周神经毒性。结论:应用紫杉醇顺铂方案联合自体CIK细胞输注治疗Ⅳ期食道癌,疗效突出,毒性反应轻微,治疗顺应性好,提高了患者的生存质量,值得进一步推广。     

Phase I Trial of Brentuximab Vedotin for Steroid-Refractory Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

We conducted a phase I study of brentuximab vedotin (BV), an antibody–drug conjugate targeting CD30, for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD). A modified 3?+?3 study design was used with the primary endpoint to determine the maximum tolerated dose of BV in this population. Escalating doses of BV were planned, starting with .6?mg/kg every 3 weeks (dose level 0) and increasing by .3?mg/kg per dose level. BV was administered in 21-day cycles for up to 16 cycles of therapy. Nineteen patients were enrolled on the study, with 2 withdrawing consent before dosing. The median number of cycles of therapy was 4 (range, 1 to 16). Reasons for stopping therapy prematurely included toxicities (n?=?9), patient decision (n?=?3), lack of response (n?=?2), and death (n?=?1). There were 2 dose-limiting toxicities observed: posterior reversible encephalopathy syndrome (cohort 4, grade 3) and sepsis (cohort 4, grade 4). The maximum tolerated dose was not reached because the trial was prematurely closed due to toxicity. Seven patients (41%) developed grade 3 or 4 adverse events that were attributed to therapy, including 4 patients who developed moderate or severe peripheral neuropathy that led to cessation of treatment in each case. According to National Institutes of Health cGVHD response criteria, 8 patients (47%) experienced a partial response, whereas 9 patients (53%) had a lack of response. There were no complete responses observed. Eleven patients (65%) were able to decrease their systemic corticosteroid dose by ≥50% by 6 months after initiation of BV, including 3 patients who were able to stop corticosteroids completely. The median soluble CD30 level before therapy was 61.5?ng/mL (range, 7.8 to 474.9); however, we did not observe any association between soluble CD30 level and cGVHD severity at enrollment or clinical responses to BV. In conclusion, BV may have activity in treatment of steroid-refractory cGVHD, yet its use is limited by treatment-emergent toxicities, including peripheral neuropathy. Continued efforts to investigate targeted approaches to cGVHD that do not cause broad immunosuppression are needed.     

Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C

One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.     

替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌的临床研究

目的：比较替吉奥单药与吉西他滨单药一线治疗老年人晚期胰腺癌的近期疗效、无进展生存和安全性。方法：回顾性分析我院自2009年1月-2014年8月收治的老年晚期胰腺癌患者44例,一线采用替吉奥单药或吉西他滨单药化疗。替吉奥组21例,吉西他滨组23例。每例患者至少接受化疗2个周期以上。每2个周期复查CT,根据实体瘤疗效评价标准（Response Evaluation Criteria In Solid Tu m o r s,R ECI ST）和美国国家癌症研究所化疗毒性分级标准（Nat i o n a l Ca n c e r In s t i t u te Co m m o n Te r m i n o l o g y C r i t e r i a Fo r A d v e r s e Ev e n t s,N C I-C TC A E）对两组治疗的近期疗效、无进展生存（progression-f ree sur v ival,PFS）和不良反应进行评估。结果：44例老年晚期胰腺癌患者经替吉奥或吉西他滨单药化疗,两组的有效率（objective response rate,ORR）及疾病控制率（disease control rate,D CR）相似,差异无统计学意义（P〉0.05）。替吉奥组中位PFS3.6月,吉西他滨组中位PFS4.0月,差异无统计学意义（P〉0.05）。替吉奥组的骨髓抑制情况明显低于吉西他滨组,其中中性粒细胞减少差异有统计学意义（P=0.01）。其它的药物相关不良反应主要为1-2级胃肠道反应和肝功能异常。结论：替吉奥单药对比吉西他滨单药一线治疗老年晚期胰腺癌,两组疗效相似,但替吉奥的化疗毒性反应明显较小,患者能耐受,口服给药方便,可推荐作为老年晚期胰腺癌的一线化疗方案,尤其可能适用于PS评分2分的不能耐受吉西他滨或其他联合方案的老年晚期胰腺癌患者。     

贝伐单抗联合卡培他滨一线治疗老年转移性结直肠癌患者的疗效和安全性

目的:评估贝伐单抗和卡培他滨的联合方案在老年转移性结直肠癌(metastatic colon or rectal cancer,mCRC)患者一线治疗中的疗效和安全性.方法:收集2013年1月至2016年12月入住首都医科大学附属北京友谊医院76例使用贝伐单抗(5～7.5 mg/kg,d1,q3w)联合卡培他滨(1000～1250 mg/m2,bid,d1～14,q3w)一线治疗老年mCRC的病例进行分析,分析疗效及不良反应(adverse events,AE).结果:经贝伐单抗联合卡培他滨方案治疗,患者总体有效率为36％,疾病控制率为73％;中位无进展生存期和总生存期分别为10.6个月和18.2个月;39例(51％)患者发生3/4级AE,最常见的为手足综合征(18％)、腹泻(10％)和深静脉血栓形成(7％);4名患者因治疗相关的AE死亡.结论:对于不适合接受多药联合化疗的老年患者,贝伐单抗联合卡培他滨是一种有效的治疗选择.     

不同双联抗血小板治疗时间对FIREBIRD支架置入患者的影响

背景：研究表明,支架内血栓直接影响了药物洗脱支架置入后近远期疗效。 目的：观察分析不同时间的双联抗血小板治疗对Firebird支架置入后冠心病患者心血管不良事件发生率的影响。 方法：选择置入Firebird国产雷帕霉素洗脱支架的患者1 107例,分为阿司匹林+硫酸氯吡格雷3月以内、3~6个月、< 6~12个月组,记录患者心血管不良事件发生率,药物不良反应的发生率及材料宿主反应。 结果与结论：实际随访例数为1 059例(共置入支架1 431枚),随访时间由7~59个月不等,临床随访率为95.7%。3月以内、3~6个月、< 6~12个月组患者主要心血管不良事件(MACE)发生率分别为8.9%,7.7%,4.4%,差异有显著性意义。3组患者心力衰竭、急性心肌梗死、再次血运重建和主要心脏事件发生率差异均有显著性意义(P < 0.05或< 0.01),< 6~12个月组发生率最低。各组患者均未发生材料宿主反应。提示,国产Firebird雷帕霉素洗脱支架置入后延长口服氯吡格雷时间至12个月甚至更长患者心血管事件的发生率降低,且不增加药物不良事件的发生率。