A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer

IntroductionChemotherapy eliminates most of the cancer cells except those with potential for self-renewal and tumor initiation, called cancer stem cells (CSCs). Chloroquine, through bioinformatics, was found to be a potential agent to target CSCs. We designed a phase II trial to test the efficacy and safety of chloroquine in combination with taxane or taxane-like chemotherapy agents in patients with advanced or metastatic breast cancer who are refractory to anthracycline-based chemotherapy.Patients and MethodsFemale patients ≥ 18 years of age who had received prior anthracycline chemotherapy were enrolled in this study. Chloroquine 250 mg was given daily orally with either docetaxel or paclitaxel or nab-paclitaxel or ixabepilone every 3 weeks. The maximum number of 3-week cycles allowed was 6. The primary efficacy endpoint was the objective response rate (ORR). The secondary efficacy endpoints included progression-free survival (PFS) and safety analysis.ResultsThirty-eight patients were enrolled in the study, and 31 patients were evaluated for response. The median age was 54.1 years (range, 31.7-78.1 years). The ORR was 45.16% (95% confidence interval [CI], 29.2%-62.2%), which was higher than the expected ORR of 30% (P = .03). Patients were followed for a median of 25.4 months and experienced a median PFS of 12.4 months (95% CI, 4.9-24.6 months) and a median OS of 25.4 months (95% CI, 13.7-83.5 months). The combination was well-tolerated, with only 13.15% of patients experiencing grade ≥ 3 adverse events.ConclusionA combination of chloroquine with taxane or taxane-like chemotherapy was efficacious in patients with locally advanced or metastatic breast cancer with prior anthracycline-based chemotherapy.     

A comparison between raltitrexed plus cisplatin and docetaxel plus cisplatin in concurrent chemoradiation for non-surgical esophageal squamous cell carcinoma

PurposeChemoradiotherapy (CRT) is considered as a standard treatment for unresectable and inoperable esophageal cancer (EC) patients. However, no consensus has been reached regarding the optimal synchronous chemotherapy regimen and the best combination of radiotherapy and chemotherapy. The aim of this study was to evaluate the efficacy and toxicity of raltitrexed plus cisplatin and docetaxel plus cisplatin to find a safe and effective concurrent chemotherapy schedule.Patients and methodsOur retrospective study included 151 EC patients treated with raltitrexed and cisplatin (RP) (n = 90) or docetaxel and cisplatin (DP) (n = 61) from 2011 till 2018. Survival outcomes and treatment related toxicity were analyzed between the two groups.ResultsPFS and OS were 18 and 34 months in the RP group, while 13 and 20 months in the DP group (P = 0.118 and P = 0.270). The 1-, 2-, 3-year survival rates of the RP group were 71.1, 55.4 and 46.4%. For the DP group, these were 63.9, 44.3 and 37.6%, respectively. Compared with DP group, RP group received a superior CR rate (68.9% versus 52.5%, P = 0.041). There was a trend that the total number of toxic reactions in RP group was lower than that in DP group (P = 0.058).ConclusionsEven RP and DP groups have the similar survival outcomes and toxicity, raltitrexed/cisplatin get a higher complete response rate. Our study suggests that raltitrexed combined with cisplatin is a safe and effective concurrent chemotherapy regimen and it might be used as an alternative for cisplatin/5-FU and cisplatin/docetaxel in CCRT for EC patients.     

Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles

Hydrophobically modified glycol chitosan (HGC) nanoparticles, a new nano-sized drug carrier, were prepared by introducing a hydrophobic molecule, cholanic acid, to water soluble glycol chitosan. The HGC nanoparticles were easily loaded with the anticancer drug docetaxel (DTX) using a dialysis method, and the resulting docetaxel-loaded HGC (DTX-HGC) nanoparticles formed spontaneously self-assembled aggregates with a mean diameter of 350 nm in aqueous condition. The DTX-HGC nanoparticles were well dispersed and stable for 2 weeks under physiological conditions (pH 7.4 and 37°C) and a sustained drug release profile, in vitro. In addition, the DTX-HGC nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the DTX-HGC nanoparticles might also be stable in the blood stream. The DTX-HGC nanoparticles exhibited a distinctive deformability in aqueous conditions, in that they could easily pass through a filter membrane with 200 nm pores despite their mean diameter of 350 nm. We also evaluated the time-dependent excretion profile, in vivo biodistribution, prolonged circulation time, and tumor targeting ability of DTX-HGC nanoparticles by using a non-invasive live animal imaging technology. Finally, under optimal conditions for cancer therapy, the DTX-HGC nanoparticles showed higher antitumor efficacy such as reduced tumor volume and increased survival rate in A549 lung cancer cells-bearing mice and strongly reduced the anticancer drug toxicity compared to that of free DTX in tumor-bearing mice. Together our results showed that the anticancer loaded nano-sized drug carriers are a promising nano-sized drug formulation for cancer therapy.     

Retrospective efficacy and safety analyses of erlotinib,pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer

ObjectiveSeveral guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non-squamous NSCLC.Materials and methodsWe analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild-type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011. Variability among patient backgrounds was evaluated using propensity scores to assess comparability. The efficacy of these agents was evaluated in patient subgroups with low variability.ResultsThe propensity scores showed that the backgrounds of the groups that received second-line therapy with each agent had low variability and were adequate for comparison. Patients were divided into the PS0/1 and PS2 groups for analysis. The median progression-free survival (PFS) in patients treated with erlotinib was 2.8 months in the PS0/1 group, as compared with 1.0 month in the PS0/1/2 group and 0.90 months in the PS2 group. PFS in PS0/1 patients who received erlotinib was comparable to that in PS0/1 patients who received pemetrexed (2.5 months) or docetaxel (1.9 months). Overall survival (OS) in erlotinib-, pemetrexed-, and docetaxel-treated PS0/1 patients was 16.1, 7.4 and 10.0 months, respectively. The study had limited power to detect differences in PFS and OS because of the small sample size.ConclusionsErlotinib appears to be a useful second-line option in PS0/1 patients with EGFR mutation-negative advanced non-squamous NSCLC given its mild adverse effects. The results should be carefully interpreted because of the small sample size, limited power, and retrospective nature of the study.     

TEC方案化疗后乳腺癌患者的早期心脏毒性

目的 观察多西他赛、表柔比星、环磷酰胺(TEC)联合化疗对乳腺癌患者早期心脏毒性影响.方法 收集2009年12月～2011年6月共71例乳腺癌患者,中位年龄48 (35～64)岁,术后予6个周期TEC方案化疗,化疗前及化疗结束时、结束后12h、24 h、48 h及72 h的分别检测血清心肌肌钙蛋白Ⅰ(cTnI)及检查心电图.结果 (1)患者化疗后不同时间点cTnI出现异常的比例均较化疗前明显升高(P＜0.01); (2)共有8(11.27％)例出现心电图改变,其中窦性心动过速4例(5.63％)、ST-T改变1例(1.41％)、窦性心动过缓2例(2.82％)、房室传导阻滞1例(1.41％),除1例为Ⅱ级毒性反应外,其余7例为Ⅰ级毒性反应.结论 TEC方案化疗后可引起早期心脏毒性反应.     

A Phase II Study of the Docetaxel–Carboplatin Chemotherapy Regimen in Advanced Non-Small-Cell Lung Cancer

The efficacy of the docetaxel–carboplatin combination chemotherapy was studied in various phase II studies. Based on these data we aimed to test the regimen in previously untreated patients with advanced advanced non-smoking lung cancer (NSCLC) with docetaxel 80 mg/m² a standard dose of carboplatin at AUC = 5, in an attempt to define the efficacy and tolerability of the combination in an open-label phase II study. Patients with histologically confirmed advanced NSCLC stage IIIB and IV were candidates for the present study. Docetaxel was administered at 80 mg/m² over 1 h by intravenous (IV) infusion followed by carboplatin AUC = 5 in 30 min IV infusion, both on day 1, and recycled every 21 days. Sixty patients received 263 courses of therapy in total; 231/263 (88%) were administered according to the planned doses, and 48/60 (80%) patients received chemotherapy without decrement of the dose; 32/263 (12%) of the courses were administered with a 10%–30% dose reduction. Complete responses (CR) were seen in 5 patients (8.3%) and partial responses (PR) in 16 patients (26.7%) for an overall response rate of 35%. Median duration of response was 7.5 months [95% confidence interval (CI)-7.1–7.9], time to progression (TIP) 11.5 months (95% CI-8.2–14.8), median overall survival (OS) 15.0 months (95% CI-10.8–19.2). One-year survival was 61.7%. Toxicity was acceptable; it was calculated according to the administered cycles and was mainly neutropenia: grade 3, 9% and grade 4, 2%; anemia: grade 3, 8%; nausea and vomiting: grade 3, 8%. The outpatient regimen of docetaxel–carboplatin is effective with acceptable toxicity in patients with advanced NSCLC.     

奈达铂联合多西他赛治疗晚期非小细胞肺癌临床疗效及其对于细胞免疫功能的影响

目的：研究奈达铂联合多西他赛治疗晚期非小细胞肺癌临床疗效及其对于细胞免疫功能的影响。方法：研究共对96例晚期非小细胞肺癌患者进行了研究,将入组患者随机分为观察组和对照组,每组48例,观察组接受奈达铂联合多西他赛治疗,对照组接受顺铂联合紫杉醇治疗。对照两组疗效,生存率、无疾病进展时间、T淋巴细胞亚群水平以及并发症的发生情况。结果：观察组的部分缓解（PR）率高于对照组,进展（PD）率低于对照组;对照组治疗后的NK、CD3^＋、以及CD4^＋/CD8^＋水平均低于治疗前,CD8^＋水平高于治疗前,差异均具有统计学意义（P〈0.05）;观察组的NK、CD3^＋、以及CD4^＋/CD8^＋水平均高于对照组,CD8^＋水平低于对照组,差异均具有统计学意义（P〈0.05）;观察组的1年生存率高于对照组,无疾病进展时间长于对照组。结论：奈达铂联合多西他赛治疗晚期非小细胞肺癌可以取得良好的疗效,且生存率高,无疾病进展时间长,而且对于患者细胞免疫功能影响较为轻微。     

多西紫杉醇修饰的人工晶体对眼组织相容性的影响

目的 探讨多西紫杉醇修饰的人工晶体对眼组织相容性的影响,为人工晶体的新型生物材料提供依据。方法 通过空气等离子技术,用多西紫杉醇对疏水性人工晶体表面进行修饰处理。16只日本大耳白兔随机分为对照组和实验组,每组8只。对照组：手术植入疏水性人工晶体;实验组：手术植入表面经多西紫杉醇修饰后疏水性人工晶体。比较人工晶体经多西紫杉醇处理后和处理前其表面亲水性的变化,两组均在手术后24h通过闪耀斑发生情况评估炎症感染程度,光镜下观察人工晶体周围组织炎症反应情况。结果 通过对比多西紫杉醇处理前后的人工晶体亲水性改变,结果显示经过多西紫杉醇处理后晶体的亲水性明显增加,主要表现是接触角差异（78±6°VS 158±9°）,与A组比较,B组的闪耀斑明显低于A组（230±10 VS 260±13）;与A组比较,B组在术后24h植入的人工晶状体周围组织炎症细胞浸润计数结果明显低于A组（11±6 VS 103±22）。结论 多西紫杉醇可通过等离子技术修饰人工晶体表面以增加其亲水性,进而增加了人工晶体和眼组织的组织相容性。     

XELOX与DF方案治疗晚期胃癌临床疗效比较

目的比较XELOX和DF方案对晚期胃癌的临床疗效和毒副反应。方法132例晚期胃癌患者随机分为XELOX组和DF组。所有病例治疗4周期以上,按WHO标准评价并比较两组的客观疗效和毒副反应。结果XELOX组总有效率52．3％,DF组总有效率47．8％（P〉0．05）。XELOX组手足综合征的发生率为36．92％,明显高于DF组的13．43％（P〈0．05）;而骨髓抑制的发生率为41．54％,显著低于DF组的85．07％（P〈0．05）;其余各项常见的副作用未见明显差异,无统计学意义（P〉0．05）。结论XELOX方案与DF方案治疗晚期胃癌疗效相当,而XELOX方案骨髓抑制副反应小,耐受性好,更易为老年患者所接受。     

Choix des nouveaux traitements médicaux dans le cancer de la prostate résistant à la castration: marqueurs prédictifs et évaluation de l’effi cacité

IntroductionDocetaxel has been the cornerstone in the treatment of castration- resistant prostate cancer (CRPC) since 2004. The recent and almost simultaneous arrival of new and effective molecules – several of which are already available on the market – has added to the CRPC treatment arsenal. Several studies have explored the optimal order in which these new treatments should be administered. The aim of this review was to present their respective predictive and evaluative factors and suggest potential administration sequences.MethodsThe PubMed medical literature citations database was searched using the following key words: prostate cancer, castration resistant, metastatic, targeted therapy, treatment sequence, immunotherapy and clinical trials. The reports of the most recent European and North American congresses were also included.ResultsWhile no predictive factors have been clearly identified for these new therapies to date, a Gleason score of not less than 8 and one or more chemotherapy sessions seemed to be predictive of lower efficacy for abiraterone. Promising elements for further investigation include the circulating tumour cell count and variation in this count per treatment, ERG mutation status or the intratumoural androgen status. Substitution criteria have not yet been reported but, as is the case with all hormone therapies, changes in PSA levels emerge as a valuable indicator of the efficacy of abiraterone. The best treatment sequence for patients who develop castration-resistance remains to be defined.ConclusionAlthough new molecules have recently become available, the experience with their use is limited. Thus, no predictive markers of response rates and treatment outcomes or data concerning the best treatment sequence to use in patients with CRPC are as yet available.