A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective:To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after first-line chemotherapy in Chinese population. Methods:Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time (OS), the second end point was disease control rate (DCR) and progression-free survival time (PFS). DCR included complete response (CR) plus partial response (PR) and plus stable disease (SD). The impact of epidermal growth factor receptor (EGFR) mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography (DHPLC). Results:Among 75 enrolled patients, the overall response rate was 37% and the DCR (CR + PR +SD) was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type (25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively). In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS (P=0.029 and 0.017, respectively), however, rash status was the predictor in terms of PFS (P=0.027).Conclusion:Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.     

mEOF方案与mFOLFOX6方案治疗晚期胃癌的疗效比较

目的:观察和比较mEOF方案（表阿霉素+奥沙利铂+5-氟尿嘧啶）与mFOLFOX6方案（奥沙利铂+ 5-氟尿嘧啶+亚叶酸钙）治疗晚期胃癌的临床疗效、毒副反应、平均住院时间及花费。方法:回顾性分析38例接受mEOF（16例）和mFOLFOX6（22例）方案化疗的晚期胃癌患者,每2个化疗周期后采用RECIST 1.1标准进行疗效评价,每个化疗周期根据NCI-CTC 3.0标准记录毒副反应,每个化疗周期的住院时间及花费从本院的医疗系统（HIS）中采集。结果:mEOF组CR 0例,PR 1例,SD 9例,PD 6例,RR为6.3%,DCR为62.5％,中位PFS为2.2个月;mFOLFOX6组CR 0例,PR 2例,SD 13例,PD 4例,RR为10.5%,DCR为78.9%,中位PFS为5.2个月,两组疗效差异无统计学意义;在对患者的生活质量影响上,mFOLFOX6方案能更好的改善患者的生活质量（P=0.014）;主要毒副反应为骨髓抑制、胃肠道反应,以Ⅰ/Ⅱ度为主,其中,mFOLFOX6组白细胞减少发生率显著高于mEOF组（P=0.009）;mEOF组血小板减少发生率显著高于mFOLFOX6组（P=0.019）。在住院时间及花费方面,mEOF组平均住院时间及费用都明显低于mFOLFOX6组（P=0.00）。结论:mEOF方案和mFOLFOX6方案治疗晚期胃癌疗效相近,毒副反应可耐受,mFOLFOX6方案在改善患者的生活质量方面有优势,mEOF组平均住院时间及费用低于mFOLFOX6组。     

阿帕替尼治疗化疗失败的转移性结直肠癌近期疗效及预后分析

  目的  评价阿帕替尼单药或联合化疗治疗转移性结直肠癌的近期疗效及耐受性。  方法  选取2016年1月至2017年12月唐山市人民医院收治的化疗失败的转移性结直肠癌患者23例,病理均经肠镜或手术证实,术后按结直肠癌诊疗规范行化疗,一线或二线化疗进展后进入阿帕替尼单药或联合化疗。单药阿帕替尼组16例,口服阿帕替尼联合化疗组7例,前3个月剂量250~500 mg,每个月评价可测量病灶,3个月以后每3个月应用CT评价疗效,评估阿帕替尼治疗的有效性及不良反应。  结果  所有患者中,无完全缓解（complete response,CR）,部分缓解（partial response,PR）9例,病情稳定（stable disease,SD）7例,疾病进展（progressive disease,PD）7例,客观缓解率（overall response rate,ORR）为39.13%,疾病控制率（disease control rate,DCR）为69.56%,疾病无进展生存时间（progressionfree survival,PFS）为1~19.0个月,中位PFS为5.0个月。单药阿帕替尼组无CR,PR 5例,SD 5例,PD 6例,ORR为31.25%,DCR为62.50%,中位PFS为4.5个月。阿帕替尼联合化疗组无CR,PR 4例,SD 2例,PD 1例,ORR为57.10%,DCR为85.70%,中位PFS为12.0个月。Log-Rank单因素分析显示,同步化疗、阿帕替尼剂量、LDH升高、低蛋白血症及疗效评价与PFS相关（均P < 0.05）;同步化疗、阿帕替尼剂量、血红蛋白降低、CD4+淋巴细胞下降及疗效评价与OS相关（均P < 0.05）。Cox回归多因素分析显示,LDH升高为PFS的独立影响因素,上述因素与OS差异无统计学意义（P>0.05）。两组患者不良反应以轻度高血压、蛋白尿、手足综合征为主,差异无统计学意义（均P>0.05）。  结论  阿帕替尼联合化疗可改善化疗失败的转移性结直肠癌患者PFS,可作为转移性结直肠癌治疗的一种有效方法。      

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

雷替曲塞联合奥沙利铂二线治疗晚期胃癌的疗效及安全性

目的:观察雷替曲塞联合奥沙利铂二线治疗晚期胃癌的疗效及安全性。方法:选取2010年1月至2015年10月化疗失败后的30 例晚期胃癌患者，随机分成2组（各15例），一组予雷替曲塞联合奥沙利铂治疗（观察组），即雷替曲塞3 mg/m2，d1；奥沙利铂85 mg/m2，d1。另一组予卡培他滨联合奥沙利铂治疗（对照组），即卡培他滨 1 000 mg/m2，bid po，d1~14，奥沙利铂 130 mg/m2，d1。以上两组方案21 d 为1个周期，每2 个周期评价疗效。结果:观察组 vs 对照组疾病控制率（DCR）73.33% vs 66.67%（P=0.69），总有效率（RR）20% vs 13.33%（P=0.62），中位无进展生存时间（mPFS）3.91 个月 vs 3.72个月（P=0.32），中位生存时间（mOS）8.07个月 vs 6.48个月（P=0.64）。恶心、呕吐发生率、白细胞减少、血小板减少、周围神经毒性、口腔黏膜炎、腹泻、转氨酶升高及心脏毒性，两组比较无差异。结论:对于晚期胃癌的二线化疗，雷替曲塞联合奥沙利铂疗效不劣于其他方案，且毒副反应可耐受，可作为晚期胃癌的一种治疗选择。     

Clinical Efficacy of Bevacizumab Concomitant with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients withadvanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomlydivided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessedfor disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinicalefficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), diseasecontrol rate (DCR) and rate of adverse responses between two groups were observed and compared. Results:ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group,respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexedgroup were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groupsincluded high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomitingand proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitantwith pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients withadvanced NSCLC.     

卡培他滨节拍化疗在晚期三阴性乳腺癌维持治疗中的疗效观察北大核心

目的:探讨卡培他滨节拍化疗在晚期三阴性乳腺癌患者维持治疗中的近远期疗效、生活质量以及不良反应。方法:将经联合化疗有效的58例晚期三阴性乳腺癌患者随机分为卡培他滨节拍化疗组和卡培他滨常规剂量组两组,每组患者各29例。节拍化疗组患者给予卡培他滨节拍化疗,常规剂量组患者给予常规剂量卡培他滨化疗。治疗2个月后评价近期疗效,每个月评价不良反应,并统计两组患者的中位疾病进展时间、中位生存时间、1年生存率、2年生存率和生活质量的变化。结果:58例患者均可评价疗效。节拍化疗组患者中CR 0例,PR 5例,SD 22例,PD 2例,客观缓解率(ORR)和疾病控制率(DCR)分别为17.2%和93.1%;常规剂量组患者中CR 0例,PR 6例,SD 20例,PD 3例,客观缓解率(ORR)和疾病控制率(DCR)分别为20.7%和89.7%。两组患者的ORR和DCR相比差异无统计学意义(P>0.05)。节拍化疗组患者的中位肿瘤无进展生存时间(PFS)为7.1个月,与常规剂量组患者(6.9个月)比较,差异无统计学意义(P>0.05);节拍化疗组患者的1年、2年生存率分别为72.4%、58.6%,与常规剂量组患者(69.0%、55.2%)比较,差异无统计学意义(P>0.05)。生活质量改善方面,节拍化疗组患者显著优于常规剂量组患者(P<0.05);节拍化疗组患者的主要不良反应为骨髓抑制、消化道反应和手足综合征等,均以Ⅰ-Ⅱ度为主,均可耐受,常规剂量组患者的消化道反应、骨髓抑制、手足综合征等不良反应的发生率和严重程度均显著高于节拍化疗组(P<0.05)。结论:卡培他滨节拍化疗作为晚期三阴性乳腺癌患者的维持治疗,其近远期疗效与常规剂量维持化疗相当,同时可提高患者生活质量,不良反应轻且发生率低,值得临床推广应用。     

EGFR-TKIs维持治疗晚期肺腺癌的临床效果

目的：探讨EGFR-TKIs维持治疗晚期肺腺癌的疗效。方法选取肺腺癌58例,按治疗方法不同,一线化疗后EGFR-TKIs维持治疗组32例,一线化疗后观察或最佳支持治疗组26例。维持治疗组距末次化疗21 d后,开始口服吉非替尼或厄洛替尼,每8周复查病灶,持续至疾病进展死亡或因不能耐受的不良反应而终止治疗。结果32例维持治疗组患者中,CR 0例,PR 9例,SD 15例,PD 8例,客观缓解率ORR（ CR＋PR）为28．1％,疾病控制率DCR （ CR＋PR＋SD）为75．0％。26例观察对照组患者中,CR 0例,PR 2例,SD 9例,PD 15例,客观缓解率ORR（CR＋PR）7．7％,疾病控制率DCR （CR＋PR＋SD）42．3％。维持治疗组与观察组比较,近期疗效ORR、DCR均有统计学差异（P＜0．05）。女性疗效高于男性。基因突变阳性有效率55．0％,未知组有效率16．7％,基因敏感突变组疗效显著高于未知组。结论EGFR-TKIs维持治疗晚期肺腺癌的疗效较好,值得临床推广。     

晚期十二指肠癌肝转移一线化疗方案的临床观察

目的:探讨晚期十二指肠癌肝转移患者一线化疗方案的疗效和安全性。方法:回顾分析本院2008年6月至2016年1月收治的晚期十二指肠癌肝转移患者23例,6例未化疗,17例化疗,其中GEMOX方案8例、FOLFOX方案9例。采用Log-rank法进行生存分析。采用RECIST 1.1版与NCI-CTC 4.0版标准评价近期疗效和不良反应。结果:17例化疗患者均可评价疗效和不良反应,共完成化疗83个周期,中位化疗4个周期(2~12个周期)。GEMOX组获PR 1例、SD 5例、PD 2例,DCR为75.0%。FOLFOX组获SD 5例、PD 4例,DCR为55.6%。两组均无CR病例。23例肝转移患者的中位OS为9.8个月。17例化疗患者的中位OS为13.2个月,6例未化疗患者的中位OS为4.4个月,差异有统计学意义(P=0.032)。GEMOX组的中位OS为13.2个月,FOLFOX组的中位OS为10.3个月,差异无统计学意义(P=0.816)。GEMOX组的中位PFS为4.9个月,FOLFOX组的中位PFS为2.5个月,差异无统计学意义(P=0.468)。常见不良反应多为1-2级,主要为白细胞减少、中性粒细胞减少、贫血、乏力及恶心等。结论:肝转移影响晚期十二指肠癌患者的预后。化疗可延长晚期十二指肠癌肝转移患者的生存。GEMOX方案和FOLFOX方案均对晚期十二指肠癌肝转移一线治疗有效,且耐受性良好。GEMOX方案可能有更好的生存获益。     

GEMOX方案和FOLFOX方案一线治疗晚期十二指肠癌的疗效观察

目的 探讨GEMOX方案和FOLFOX方案一线治疗晚期十二指肠癌的疗效和安全性。方法 回顾分析本院2008年6月至2016年1月收治的30例晚期十二指肠癌患者的临床及随访资料,其中10例未接受化疗,20例接受化疗（GEMOX方案9例、FOLFOX方案11例）,分别采用RECIST 1.1版与NCI-CTC 4.0版标准评价疗效和不良反应,Kaplan-Meier法进行生存分析。结果 GEMOX方案和FOLFOX方案均无CR和PR病例,其中GEMOX方案获SD 6例、PD 3例,疾病控制率（DCR）为66.7％,FOLFOX方案获SD 4例、PD 7例,DCR为36.4％,两组DCR的差异无统计学意义（P＞0.05）。GEMOX方案和FOLFOX方案的中位总生存期（OS）分别为27.9个月和15.2个月（P=0.179）;GEMOX方案的中位无进展生存期（PFS）为8.0个月,优于FOLFOX方案的4.4个月,差异有统计学意义（P=0.038）。常见不良反应多为1～2级,主要为白细胞减少、中性粒细胞减少、乏力、恶心、皮疹等。20例接受化疗患者的中位OS为26.9个月,优于10例未接受化疗的4.4个月,差异有统计学意义（P＜0.001）。结论 化疗可延长晚期十二指肠癌患者的生存时间。GEMOX方案和FOLFOX方案均对晚期十二指肠癌一线治疗有效,且耐受性良好,其中GEMOX方案的中位PFS可能更长。     

聚乙二醇化脂质体多柔比星联合异环磷酰胺治疗晚期转移性软组织肉瘤

背景与目的：软组织肉瘤一旦出现远处转移,预后极差,中位生存时间不到1年。多柔比星联合异环磷酰胺(ifosfamide,IFO)(AI方案)是晚期软组织肉瘤常用的一线联合治疗方案。聚乙二醇脂质体多柔比星(pegylated liposomal doxorubicin,PLD)活性成分为盐酸多柔比星,药物包裹在脂质体中,可减少多柔比星的临床毒性反应。该研究探讨PLD联合IFO治疗晚期转移性软组织肉瘤的临床疗效和安全性。方法：选取晚期转移性软组织肉瘤患者25例,使用PLD联合IFO方案,PLD剂量30 mg/m²,静脉滴注,第1天;IFO剂量1.8 g/m²,静脉滴注,第1~5天;美司钠360 mg/m²,用IFO时0、4和8 h,21 d为1个周期。结果：所有患者化疗1~8个周期,中位周期数4。25例患者中部分缓解9例(36%),疾病稳定12例(48%),疾病进展4例(16%),疾病控制率(完全缓解+部分缓解+疾病稳定)为84%(21/25)。中位无进展生存时间为7.3个月(95%CI：4.6~10.0个月)。由于失访病例较多,中位总生存时间未随访到。化疗后3/4级不良反应包括白细胞下降(20%)、粒细胞下降(28%)、贫血(4%)和呕吐(4%)。只有1例患者治疗过程中予以减量。结论：临床应用PLD联合IFO方案治疗晚期转移性软组织肉瘤疗效确切,且毒性反应较轻,值得进一步深入研究。     

晚期非小细胞肺癌一线化疗疗效与生存关系的分析

背景与目的第三代新药组成的方案在晚期NSCLC一线化疗中使大部分患者能够取得疾病控制(CR PR SD),我们进行了本项回顾性分析以探讨一线化疗疾病控制与疾病未控(PD)患者之间生存的差别,以及疾病控制患者有效(CR PR)和稳定(SD)患者之间生存的差别,明确与患者生存有关的预后因素。方法本项回顾性分析纳入了完成第三代新药组成的铂类或非铂类方案一线化疗的118例IIIB期(伴恶性胸水)/IV期NSCLC患者,一线化疗的疗效按RECIST标准根据影像学结果评价为CR,PR,SD,PD四种情况。结果一线化疗后CR PR SD共86例(72.9%)[其中CR2例(1.7%),PR47例(39.8%),SD37例(31.4%)],PD32例(27.1%)。CR PR SD和PD患者MST有统计学差别,为17.8月和8.4月(P=0.001)。CR PR和SD患者MST无统计学差别,为18.1月和15.5月(P=0.917),中位PFS无统计学差别,为7.1月和6.9月(P=0.622)。Cox多因素回归分析显示分期(IIIB期或IV期)、化疗线程(≤3线或≥4线)、一线化疗疾病是否控制是总生存的独立预后因素。结论本研究结果表明,晚期NSCLC患者一线化疗有效和稳定的患者其生存较进展患者好,疾病稳定患者的生存获益与有效患者无明显差别。     

30例自体外周造血干细胞移植治疗多发性骨髓瘤的疗效及预后因素评价

目的:对30例多发性骨髓瘤（multiple myeloma,MM）患者经自体外周造血干细胞移植（autologous hematopoietic stem cell transplantation ,APBSCT）治疗后的临床疗效进行评估,并分析可能影响预后的因素。方法:30例MM患者有2 例复发行2 次APBSCT,因此共计移植32例次。移植前予常规联合化疗（11例含万珂）,化疗联合G-CSF 动员APBSC ,选择以马法兰为基础的预处理方案,d0 天回输。结果:动员后患者采集的单个核细胞（MNC）中位数为6.41× 108/kg,CD34+细胞4.75× 106/kg。APBSCT后中位中性粒细胞和血小板重建时间分别为9.5 天和11天。APBSCT后CR和VGPR 率分别为37.5% 和34.4% ,中位生存期（overallsurvival ,OS）为67.27个月,中位无进展生存期（progression-freesurvival ,PFS）为29.77个月,其中CR组、PR组中位PFS 分别为29个月、20个月,VGPR 组中位PFS 未达到,CR+VGPR组与PR组PFS 比较P=0.025。万珂组和非万珂组CR率分别为63.6% 和23.8%（P=0.034）,万珂组中位OS及PFS 均未达到,非万珂组中位PFS 为22个月（P=0.045）。 结论:硼替佐米诱导序贯APBSCT可获得更长的无病生存。APBSCT作为MM诱导缓解后的强化治疗,缓解率高,且移植后获得VGPR 以上反应的患者PFS 获益。      

晚期NSCLC一线化疗疾病控制与生存关系的分析

目的回顾性分析一线化疗疾病控制（DCR）与进展（PD）患者之间生存的差别,探讨DCR可否预测生存。方法本文回顾性分析本院一线含铂联合化疗86例ⅢB期/Ⅳ期非小细胞肺癌（NSCLC）患者,化疗的疗效按WHO标准分为CR,PR,SD,PD。结果一线化疗后DCR共64例（74.4%）[其中CR 0例,PR 30例（34.9%）,SD 34例（39.5%）],PD 22例（25.6%）。DCR和PD患者中位生存期（MST）有统计学意义,为14.2月和5.1月（P〈0.001）。CR＋PR和SD患者MST有统计学意义,为15.0月和11.0月（P=0.030）。COX多因素回归分析显示一线化疗疾病控制（P=0.017）,ECOG评分（P=0.046）是总生存的独立预后因素。结论本研究提示晚期NSCLC患者一线化疗疾病控制患者其生存较进展患者好,疾病控制比化疗有效似乎更能反映化疗疗效,预测生存期。     

TUBB3的表达对晚期胃癌紫杉类药物化疗疗效和预后的影响

  目的  检测晚期胃癌组织中β-微管蛋白Ⅲ(class Ⅲ β-tubulin,TUBB3)的表达,分析TUBB3的表达与紫杉类药物化疗疗效及患者预后的相关性。  方法  选取邵阳市中心医院2008年12月至2011年12月接受含多西他赛或紫杉醇为基础化疗的晚期胃癌患者49例,免疫组织化学检测胃癌组织中TUBB3蛋白的表达水平,分析TUBB3的表达与化疗疗效、无进展生存期(progressionfree survival,PFS)和总生存期(overall survival,OS)的关系。  结果  49例患者接受含多西他赛或紫杉醇为基础的化疗,有3例患者因组织标本太少被剔除,化疗疗效达完全缓解(complete response,CR)1例、部分缓解(partial response,PR)17例、稳定(stable disease,SD)22例、进展(progression disease,PD)6例,化疗总有效率(CR+PR)为39.13%(18/46),TUBB3低表达组有效率为54.17%,TUBB3高表达组有效率为22.73%,两者比较差异具有统计学意义(χ2=4.736,P=0.029)。TUBB3低表达组患者的中位PFS和OS分别为5.9个月和11.6个月,TUBB3高表达组患者的中位PFS和OS分别为3.9个月和7.9个月,TUBB3低表达组较高表达组的PFS和OS均延长,差异有统计学意义(PFS:P=0.032;OS:P=0.001)。单因素及多因素分析得出,TUBB3均为晚期胃癌的独立预后因素。  结论  晚期胃癌组织中TUBB3的表达与紫杉类药物化疗疗效及预后具有相关性,低表达组的化疗疗效及生存预后好于高表达组。可为临床上晚期胃癌个体化治疗的制定及判断预后提供参考。      

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)

Purpose: The aim of this study was to determine the efficacy and safety of docetaxel plus epirubicin combination as first-line chemotherapy in patients with locally advanced and/or metastatic adult STS.Patients and Methods: Eighteen patients were treated with epirubicin 30 mg/m(2) on days 1 to 3 and docetaxel 100 mg/m(2) on day 1 every 3 weeks.Results: Fifteen out of 18 patients (83.4%) were assessable for response. No complete response was recorded. Three (20%) patients achieved PR, 3 had SD and 9 PD. The overall median survival was 14 months (range, 3-48 months) and the median time to disease progression was 4 months (range, 2-45 months). Grade >/= 3 neutropenia occurred in 88% and neutropenic fever in 27.8% of patients. Other toxicities were mild. No treatment related deaths occurred.Discussion: Docetaxel plus epirubicin combination achieved low response rate with severe myelotoxicity in patients with advanced STS.     

Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy

BackgroundIn the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC).MethodsAfter four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]).ResultsFollowing first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life.ConclusionsPatients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.     

Bevacizumab in Combination with Metronomic Chemotherapy in Patients with Anthracycline- and Taxane-Refractory Breast Cancer

Abstract

A vascular endothelial growth factor (VEGF) inhibitor might enhance metronomic chemotherapy in previously treated metastatic breast cancer (MBC) patients. Anthra-cycline and taxane refractory MBC patients were given cyclophosphamide 50 mg p.o. daily, methotrexate 1 mg/kg i.v. every 14 days, and bevacizumab 10 mg/kg i.v. every 14 days. Trastuzumab was added in HER2-overexpressing tumors. 24 patients were enrolled and 22 were evaluable. All tumors had histologic grade II-III and most patients had ≥2 metastatic sites. After a median follow-up of 7.7 months the response rates were: complete response (CR) 0%, partial response (PR) 31.8% (95% CI 13.9-54.9%), stable disease for ≥24 weeks (SD) 31.8% (95% CI 13.9-54.9%). Clinical benefit (CB= CR + PR + SD>24w) 63.6% (95% CI 40.7-82.8%). Median progression-free survival (PFS) was 7.5 months; overall survival (OS) was 13.6 months. HER2-overex-pressing or high proliferative-index tumors had better 6-month PFS (75% vs. 34% in HER-negative tumors P= 0.043; 67% vs. 0% in Ki-67 ≥20% tumors, P = 0.015). Adverse effects were mild. The combination of bevacizumab and a metronomic-based chemotherapy was effective, well tolerated and provided clinical benefit in heavily-treated MBC patients.     

培美曲塞联合铂类一线治疗晚期非鳞非小细胞肺癌的临床观察

背景与目的：晚期肺癌一线化疗有效率仅30%～40%,本研究旨在探讨培美曲塞联合铂类药物(卡铂或顺铂)治疗晚期非鳞非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及不良反应。方法：121例非鳞NSCLC患者,给予培美曲塞联合铂类化疗：培美曲塞500 mg/m2第1天,静脉滴注,卡铂300 mg/m2,第1天,静脉滴注,每3周重复;或培美曲塞500 mg/m2,第1天,静脉滴注,顺铂70 mg/m2,第1天,静脉滴注,每3周重复。上述方案连用2~6个周期,至少2个周期评价疗效。主要观察终点是疾病控制率(diseasecontrol rate,DCR),其次是中位无进展生存时间(progression-free survival,PFS)、1年生存率和安全性。结果：全组可评价疗效121例,完全缓解(complete response,CR)1例,部分缓解(partial response,PR)44例,病情稳定(stable disease,SD)50例,疾病进展(progressive disease,PD)26例,客观有效率(objective response rate,ORR)为37.2%(45/121),DCR为78.5%(95/121),PFS为5.2个月(95%CI：4.4~6.0个月),1年生存率为59.0%。其中培美曲塞联合卡铂组ORR为38.3%(23/60),DCR为78.3%(47/60),PFS为5.1个月(95%CI：3.8~6.4个月),1年生存率55.2%;培美曲塞联合顺铂组ORR为36.1%(22/61),DCR为78.7%(48/61),PFS为6.2个月(95%CI：4.3~8.1个月),1年生存率为62.5%。两组之间的ORR、DCR、PFS和1年生存率差异无统计学意义(P＞0.05)。主要不良反应为中性粒细胞和白细胞下降、乏力及胃肠道反应。结论：培美曲塞联合铂类药物一线治疗晚期非鳞NSCLC疗效确切,不良反应发生率低,耐受性较好。