多西他赛联合希罗达治疗复发转移性乳腺癌的临床观察

目的:对于复发转移性乳腺癌,多西他赛和希罗达药物均有确切肯定的疗效,由于多西他赛能增强肿瘤组织的胸苷磷酸化酶(TP)活性,因而与希罗达有协同作用。本研究观察及评价多西他赛联合希罗达治疗复发转移性乳腺癌的疗效和不良反应。方法:32例复发转移性乳腺癌患者均给予多西他赛75mg/m2,第1天;希罗达口服2次/d,餐后服用,每次1250mg/m2,连续服用14d,治疗周期为21d,至少治疗2个周期。结果:本组完全缓解(CR)2例,部分缓解(PR)15例,稳定(SD)4例,疾病进展(PD)10例,总有效率53.1%,中位疾病进展时间(TTP)10个月。不同转移部位或器官的有效率分别为:软组织62.7%(10/16);肺脏50%(9/18);骨骼54.5%(6/11);肝脏30.0%(7/13)。常见不良反应为手足综合征、皮肤色素沉着、恶心、呕吐、厌食、疲劳,少数患者出现口炎、头晕、腹泻和胸闷。90.6%的患者有白细胞下降,2例Ⅳ度骨髓抑制。结论:多西他赛联合希罗达治疗晚期乳腺癌疗效肯定,患者耐受性良好。     

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.     

Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer: final results of a phase?II trial

Background  Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer. Patients and methods  A total of 51 patients were treated with NPLD (60 mg/m²) and docetaxel (75 mg/m²) in 3-weeks intervals for up to eight cycles. Results  The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9–13.1 months) and 25 months (95% CI, 22.1–29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1–16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients. Conclusions  The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.     

HPLC法测定多西他赛固体脂质纳米粒的药物含量

目的建立多西他赛固体脂质纳米粒的含量测定方法。方法采用Hypersil ODS C18柱(4.6 mm×200mm,5μm),流动相为乙腈-水(60∶40,V/V),检测波长:228 nm,流速:1 mL.min-1。结果多西他赛在0.50～50.00μg.mL-1的浓度范围内,峰面积对浓度有良好的线性关系(R2=0.999 9,n=7),方法的日内与日间精密度RSD均<2%,回收率分别为98.81%、99.22%、101.5%。结论该方法具有简便、快速、准确的特点,可用于多西他赛固体脂质纳米粒的含量测定。     

DX方案与DF方案治疗老年进展期胃癌的对比研究

目的比较多烯紫杉醇联合卡培他滨(DX)方案与多烯紫杉醇联合5-氟尿嘧啶/亚叶酸钙(DF)方案治疗老年进展期胃癌的临床疗效及安全性。方法 96例患者随机分为治疗组和对照组。治疗组(DX组)49例,应用多烯紫杉醇联合卡培他滨方案化疗:多烯紫杉醇60mg/m2,静脉滴注1h,第1天;卡培他滨1 000mg/m2,口服,2次/日,第1~14天。对照组(DF组)47例,应用多烯紫杉醇联合5-氟尿嘧啶/亚叶酸钙方案化疗:多烯紫杉醇60mg/m2,静脉滴注1h,第1天;亚叶酸钙200mg/m2,静脉滴注2h后予5-氟尿嘧啶500mg/m2,持续静脉输注22h,第1~5天;两组均3周为1周期。2周期后评价疗效。随访观察疾病进展时间和生存期。结果DX组总有效率42.86%,DF组总有效率31.91%,差异无统计学意义(P>0.05);DX组、DF组疾病控制率分别为79.59%、63.83%,两组相比差异无统计学意义(P>0.05);DX组体力状况Karnofsky评分明显高于DF组(P<0.05)。DX组手足综合征发生率明显高于DF组(P<0.05),而Ⅲ/Ⅳ度中性粒细胞下降发生率则明显低于DF组(P<0.05)。结论多烯紫杉醇联合卡培他滨方案疗效肯定、不良反应易耐受,是老年进展期胃癌较理想的化疗方案,值得临床进一步研究。     

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

Purpose: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. Methods: Forty-eight (median age 54 years, range 26–77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0–2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m² for 90 min and docetaxel infusion 80 mg/m² for 90 min, repeated once every 3 weeks. Results: Twenty-five (52.08%, 95% confidence interval [CI] 37.95–66.21) patients showed responses: 3 complete (6.25%, 95% CI 0–13.05) and 22 (45.83%, 95% CI 31.74–59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. Conclusion: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.     

紫杉醇与多烯紫杉醇

目的比较紫杉醇与多烯紫杉醇在药学特性及临床应用的差异,为临床合理应用两药提供依据。方法查阅分析相关文献资料,比较分析两药异同。结果紫杉醇与多烯紫杉醇在化学结构、药代动力学、药物相互作用、药物毒性及临床应用等方面有不同的特点。结论临床应用中应根据各自特点,注意合理使用。     

L-OHP、DOC和HCPT联合5-Fu序贯化疗治疗晚期胃癌的临床研究

目的 探讨奥沙利铂(oxaliplatin,L-OHP)、多西紫杉醇(docetaxel,DOC)和羟基喜树碱(hydroxy camptothecine,HCPT)联合5-氟尿嘧啶(5 Fluorouracil,5-Fu)/亚叶酸钙(calcium folinate,CF)组成的序贯化疗方案治疗晚期胃癌(advanced gastric cancer,AGC)的疗效和不良反应.方法 入组35例AGC患者,以序贯方式依次接受L-OHP+ 5-Fu/CF、DOC+5 Fu/CF和HCPT+ 5-Fu/CF方案化疗,每个方案连用2周期,均每3周重复,共6周期化疗;观察疗效和不良反应,并随访疾病进展情况.结果 35例均能评价疗效,总缓解率(RR)为60％(21/35),中位肿瘤进展时间(TTP)为7.6月,95％置信区间(CI)(7.0～8.2),中位生存期(OS)15.1月,95％ CI (14.2～16.0);不良反应程度较轻,主要为骨髓抑制、胃肠道反应、脱发及过敏反应,但均可逆,未出现因化疗毒性而死亡病例.结论 LOHP、DOC和HCPT联合5-Fu/CF的序贯化疗是AGC有效治疗方案,化疗耐受性好,新颖的序贯化疗模式在AGC中应用值得进一步研究.     

多西紫杉醇作为晚期非小细胞肺癌的二线治疗药物的系统评价

目的系统评价多西紫杉醇作为晚期非小细胞肺癌二线治疗药物的疗效、不良反应、生存质量及给药方案。方法电子检索Medline（1991～2008．2）、Pubmed、CBMDisc等数据库，对符合纳入标准的研究，采用RevMan4．2软件进行Meta分析。结果共有8篇文献纳入研究。多西紫杉醇治疗晚期非小细胞肺癌疗效与支持性疗法相比，疾病进展期和中位生存期明显延长，分别是10．6周和6．7周（P〈0．001）、7．0月和4．6月（P〈0．001），1年生存率分别为37％和11％。不良反应研究中，3—4级血液学不良反应在多西紫杉醇组中发生率较高，其中高剂量组（100mg／m^2）发生率高于低剂量组（75mg／m^2）；3～4级非血液学不良反应，多西紫杉醇组和支持治疗组发生率相似。另外以长春瑞滨或异环磷酰胺为对照的研究显示，多西紫杉醇组反应率、疾病进展时间和生存率优于对照；4级血液学不良反应多西紫杉醇组高于对照组，其他3～4级非血液学不良反应的发生率无明显规律。生存质量评价（LCSS、QLQ—C30或QLQ—LC13）方面，患者自评和观察者评价均显示多西紫杉醇组优于支持治疗组。不同给药方案（3周给药和1周给药）的Meta分析结果可以看出不同给药方案在疾病控制率、反应率及1年生存率方面没有统计学差异（P〉0．05）；在嗜中性白细胞减少症、白细胞减少症的发生率上，1周给药组发生率均低于3周给药组（P〈0．01）；在非血液学不良反应如虚弱、恶心／呕吐的发生率上，不同给药方案没有统计学差异（P〉0．5）。结论多西紫杉醇可以认为是在晚期非小细胞肺癌的二线治疗中疗效确切的药物；不同的多西紫杉醇给药方案（3周vs1周），在疗效方面差异不明显，在不良反应发生率上略有差异，因此，在发生严重血液学不良反应的情况下，可以用1周给药代替3周给药进行治     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应。方法晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例。用多西紫杉醇75mg／m^2,第1天静滴,顺铂25mg／m^2。第1～3天静滴,21天为1周期,2周期后评价疗效。结果31例中CR3例,PR14例,总有效率为54．84％。主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受。结论多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受。