吉西他滨联合多西紫杉醇治疗晚期软组织肉瘤

目的探讨吉西他滨联合多西紫杉醇治疗软组织肉瘤的疗效及毒性反应。方法 89例复发转移的晚期软组织肉瘤患者,采用吉西他滨900mg/m2静脉滴注90min,第1、8天;多西紫杉醇75mg/m2,静脉滴注60min,第8天;3周重复。分析肉瘤及5种组织学亚型患者的近期疗效、生存及影响因素。结果可评价近期疗效的82例患者中2例完全缓解,25例部分缓解,总有效率32.9%;平滑肌肉瘤和恶性纤维组织细胞瘤有效率分别为44.4%和40%,与其他组织学亚型之间差异有显著性（P=0.024）。83例患者可评价生存,1年生存率42.2%,2年生存率16.9%。结论吉西他滨联合多西紫杉醇是治疗复发转移晚期软组织肉瘤的有效方案,不同组织学亚型之间存在敏感性差异,毒性可以耐受。     

三氧化二砷联合吉西他滨及多西他赛治疗晚期转移性骨肉瘤26例临床分析

  目的   探讨三氧化二砷（arsenic trioxide,As₂O₃）联合吉西他滨及多西他赛治疗骨肉瘤肺转移的临床疗效。   方法   收集26例对一线化疗药物耐药的骨肉瘤肺转移患者,男性14例,女性12例,年龄11~62岁,平均31.2岁,所有患者均接受过传统规范化疗后出现肺转移。应用As₂O₃（剂量为10 mg/d,d1~28）联合吉西他滨（剂量为800 mg/m2,d1、d8）及多西他赛（剂量为75 mg/m2,d8）每3周重复给药,每2个化疗疗程复查疗效。   结果   接受化疗的患者总体有效率（CR+PR）为34.6%（9/26）。中位随访时间28.2（1~48）个月,中位总生存期（OS）为16.7个月（95%CI:7.561~18.058）和中位无进展生存期（PFS）为10.3个月（95%CI:6.541~ 8.754）,1、2和4年生存率分别是61.5%、38.4%和15.4%。治疗后最常见的不良反应为骨髓抑制,而常见的非血液学不良反应包括心脏毒性、消化道反应及肝肾功能异常,对症处理后均明显缓解。   结论   As₂O₃联合吉西他滨及多西他赛作为二线化疗药物治疗骨肉瘤肺转移的近期临床疗效较好,且有较好的耐受性。      

吉西他滨联合多西他赛治疗晚期复发转移性骨肉瘤疗效观察

目的：观察吉西他滨联合多西他赛方案治疗晚期复发转移性骨肉瘤的有效性和安全性。方法：收集2010年1月至2014年12月间我院收治的23例一线化疗失败的出现转移的晚期骨肉瘤患者,行多西他赛（75mg／m2,d1,8）联合吉西他滨（1000mg／m2,d1,8）方案行全身化疗,21天为1周期,如达到 PR 及 SD 的患者继续行原方案化疗2周期。采用 RECIST 标准1．0版评价疗效,化疗2周期后评价疗效及毒副反应,3．0版观察毒副反应。结果：23例患者均完成化疗,可评价疗效。完全缓解（CR）0例,部分缓解（PR）3例,疾病稳定（SD）9例,疾病进展（PD）11例;有效率（RR）为13．0％,疾病控制率（DCR）为52．2％,中位无进展生存时间为8．5个月,中位生存时间为16个月,主要毒副反应为限制性骨髓抑制,没有患者出现肾功能不全和过敏反应,2例出现Ⅳ级中性粒细胞减少及 1例出现Ⅳ级白细胞减少。结论：多西他赛联合吉西他滨方案二线治疗晚期复发转移性骨肉瘤疗效肯定,毒副反应可以接受。     

吉西他滨联合奥沙利铂与多西他赛联合奥沙利铂治疗晚期食管鳞癌的临床观察

目的：观察吉西他滨联合奥沙利铂及多西他赛联合奥沙利铂治疗晚期食管癌的疗效和毒副反应.方法：68例晚期食管癌患者均接受化疗,随机分为两组,每组34例患者：吉西他滨1000mg/m2,d1,8,静脉滴注30min;多西他赛75mg/m2,d1,奥沙利铂85mg/m2,d1.每3周为1个周期,2个周期后评价疗效及毒副反应.结果：两组没有观察到完全缓解病例.吉西他滨组：PR 19例,SD 9例,PD 6例,总有效率为55.9%,临床获益率 82.4%,中位疾病进展时间6.1个月;多西他赛组：PR 16例,SD 11例,PD 7例,总有效率为 47.1%,临床获益率 79.4%,中位疾病进展时间 5.1个月.两组有效率（55.9%vs 47.1%,P=0.47）、临床获益率（82.4%vs 79.4%,P=0.38）及中位无进展生存时间（6.1月 vs 5.1月,P=0.524 ）均无明显差异.主要毒副反应为血液学毒性和消化道反应,两组Ⅲ-Ⅳ度恶心呕吐发生率分别为14.7%和38.2%（P=0.028）,Ⅲ-Ⅳ度白细胞减少分别为11.8%和47.1%（P=0.001）,Ⅲ-Ⅳ度血小板减少分别为32.4%和8.8%（P=0.016）,肌肉酸痛发生率分别为8.8%和32.4%（P=0.016）,末梢神经麻木分别为11.8%和 35.3%（P=0.022）.结论：吉西他滨联合奥沙利铂及多西他赛联合奥沙利铂治疗晚期食管癌近期疗效相近,毒副反应均可耐受.     

吉西他滨/多西他赛联合铂类一线治疗转移性鼻咽癌的临床对照研究

目的:观察吉西他滨联合铂类与多西他赛联合铂类方案在转移性鼻咽癌一线治疗中的疗效及耐受性。方法:2011年1 月至 2015年12月广西医科大学第四附属医院诊疗的转移性鼻咽癌120例。随机分两组接受一线化疗:吉西他滨联合铂类组60例,多西他赛联合铂类组60例。观察疾病缓解率（RR）、疾病控制率(DCR)及不良反应;采用 Kaplan-Meier法、Log-rank检验分析中位无进展生存（mPFS）、中位总生存（mOS）。结果:113例可评价病例,吉西他滨联合组56例,多西他赛联合组57例。吉西他滨联合组RR显著高于多西他赛联合组,差异有统计学意义(71.4% vs 52.6%,P=0.04)。中位随访15.8个月,与多西他赛联合组比较,吉西他滨联合组mPFS、mOS显著延长,差异有统计学意义（mPFS:9.7个月 vs 7.8个月,P=0.014; mOS:20.6个月 vs 16.8个月,P=0.005)。两组主要不良反应为均为骨髓抑制、胃肠道反应,但差异无统计学意义（P＞0.05）。多西他赛联合组1级末梢神经损害发生率显著高于吉西他滨联合组,差异有统计学意义(12.3% vs 1.8%,P=0.030),但两组均无2～4级末梢神经损害发生。结论:与多西他赛联合铂类方案比较,吉西他滨联合铂类一线治疗转移性鼻咽癌患者有更高的RR,可显著延长患者的PFS及OS时间,耐受性良好,末梢神经毒性更轻,可作为转移性鼻咽癌一线治疗的良好选择。     

吉西他滨联合多西他赛治疗复发或难治性骨肉瘤的临床观察

目的 观察吉西他滨联合多西他赛治疗复发或难治性骨肉瘤的有效性和安全性。方法 经病理确诊的28例复发或难治性骨肉瘤患者接受吉西他滨联合多西他赛治疗,具体方案为：吉西他滨1000mg／m²,静脉滴注,d1、d8;多西他赛 75mg／m²,静脉滴注,d8,3周为1周期。化疗2个周期后,按照RECIST标准评价客观疗效。每周期按照NCI CTC 3.0分级标准评价药物毒性反应。结果 28例患者均可评价疗效,获PR 1例,SD 8例,PD 19例,有效率（RR）为3.6％（1／28）,疾病控制率（DCR）为32.1％（9／28）;中位无疾病进展时间为6.0周（6～24周）,中位总生存时间为11.0个月（3～26个月）。主要毒副反应为骨髓抑制、胃肠道反应和乏力,未出现严重不良反应。结论 吉西他滨联合多西他赛治疗复发或难治性骨肉瘤具有一定的疗效,安全性高,值得临床推广应用。     

多西他赛与吉西他滨分别联合顺铂治疗晚期 非小细胞肺癌的临床观察

 目的 评价多西他赛和吉西他滨分别联合顺铂治疗晚期非小细胞肺癌的疗效和不良反应。方法 76例晚期非小细胞肺癌患者随机分为两组：DP组：多西他赛75 mg/m2,d1,DDP 60mg/m2,d1; GP组：吉西他滨1000 mg/m2,d1,d8,顺铂用量同前。以上方案均21天为1周期,2~4周期评估疗效。结果 DP组总有效率43.5%,初治有效率53.8%,复治有效率23.0%。GP组总有效率45.9%,初治有效率56.0%,复治有效率25.0%。两组初治与复治相比,差异均有统计学意义（P<0.05）。两组的主要不良反应为骨髓抑制和消化道反应。结论 多西他赛和吉西他滨联合顺铂治疗晚期非小细胞肺癌疗效好,近期疗效相近,不良反应可耐受,初治较复治疗效好。     

吉西他滨联合多西紫杉醇方案治疗晚期肝癌的临床观察

目的评价吉西他滨联合多西紫杉醇治疗晚期肝细胞癌患者的疗效和不良反应。方法收集我科2006年2月-2010年2月间均诊断为晚期肝细胞癌患者42例。化疗方案剂量及方法设定：多西紫杉醇30 mg/m²,吉西他滨800 mg/m²在d1、d8天应用,静脉滴注。21天为 1周期,2周期后评价疗效。结果全组42例患者均可评价疗效。其中未见完全缓解患者,部分缓解率为21.4%(9/42),稳定47.6%(20/42),进展31.0%(13/42)。中位进展时间4.1月(95％CI：2.14~7.26月),中位生存时间9.2月(95％CI：4.25~18.12月)。无治疗相关死亡,主要不良反应为外周血粒细胞下降、血小板减少、轻度贫血、消化道反应、疲劳、外周神经毒性及偶发的腹泻和皮疹。结论吉西他滨联合多西他赛治疗晚期肝细胞癌具有显著的抗肿瘤作用,化疗期间出现血液学不良反应,食欲下降、乏力是普遍现象,需要临床重视。早期实施有效的干预可明显减少不良反应的发生率。     

吉西他滨治疗晚期纤维肉瘤1例

近10年来随着阿霉素、异环磷酰胺（IFO）等在软组织肉瘤中的应用,晚期软组织肉瘤的化疗有了一定进展,但二线治疗药物仍在探索中,我们试用吉西他滨（健择）治疗1例晚期纤维肉瘤,现报告如下：     

多西他赛或吉西他滨联合替吉奥二线治疗晚期食管鳞癌的临床疗效和安全性分析

目的 比较多西他赛或吉西他滨联合替吉奥二线治疗晚期食管鳞癌的临床疗效和安全性.方法 选取一线紫杉醇联合铂类化疗方案治疗失败或缓解后再进展的晚期食管鳞癌患者61例,根据二线化疗方案不同将患者分为多西他赛组和吉西他滨组,多西他赛组(n=31)给予多西他赛联合替吉奥治疗,吉西他滨组(n=30)给予吉西他滨联合替吉奥治疗.两组患者均每2个周期评价疗效,并对两组患者的疗效、不良反应发生情况、无进展生存情况进行比较.结果 多西他赛组和吉西他滨组患者的有效率(RR)分别为25.806%、16.667%,疾病控制率(DCR)分别为61.290%、56.667%,中位无进展生存期(PFS)分别为4.5个月、4.0个月,差异均无统计学意义(P>0.05).两组患者的主要不良反应均为血液学不良反应和消化道不良反应,经过对症治疗均可缓解,多西他赛组的中性粒细胞减少、血小板减少、乏力及皮疹的发生率低于吉西他滨组(P<0.05).结论 多西他赛或吉西他滨联合替吉奥药物作为二线化疗方案治疗晚期食管鳞癌疗效相当,但多西他赛相较吉西他滨可有效降低化疗不良反应发生率.     

Gemcitabine and Docetaxel as a Second-Line Treatment in Advanced Soft Tissue Sarcomas

OBJECTIVE Promising anti-tumor activity in patients with metastatic or unresectable soft tissue sarcomas has been reported with gemcitabine and/or docetaxel.METHODS Forty patients with advanced soft tissue sarcomas refractorv to first-line chemotherapv treatment were enrolled.They received:combination of gemcitabine at dose of 900 mg/m2 on days 1 and 8 and docetaxel at dose of 100 mg/m2 on day 8,and had this regimen repeated every 3 weeks. If the patients had received the Delvic irradiation in advance. aemcitabine dose was reduced to 675 mg/m2 on days 1 and 8 and docetaxel to 75 mg/m2 on day 8,and had it repeated every 3 weeks. RESULTS Gemcitabine/ docetaxel combination was well tolerated by the patients with an overall response of 20%.After median follow-up of 15 months, a median overall survival time was 12 months(95% CI 7.042-16.958)and a median progression free survival time was 6 months(95% CI 5.445-6.545).The most common hematologic toxicity was neutropenia(47.5%)while mucositis was the most common non- hematologic toxicity(45%).The 1-and 2-year survival rates were 50% and 15%,respectively.CONCLUSION This regimen of gemcitabine/docetaxel combination as second-line treatment for the patients with advanced soft tissue sarcomas is effective with acceptable toxicities. These results should be evaluated in a large phase III trial.     

A Phase Ib/II Study of Gemcitabine and Docetaxel in Combination With Pazopanib for the Neoadjuvant Treatment of Soft Tissue Sarcomas

Lessons Learned

• Our results highlight some of the challenges in the management of soft tissue sarcomas, which requires close cooperation between surgeons and medical oncologists and a careful selection of patients. The incidence of hepatotoxicity was a concerning finding and had been previously reported in patients treated with pazopanib.
• Although pharmacokinetic analysis was not part of this study, concomitant treatment with pazopanib has been recently reported to increase docetaxel exposure, which may explain the increased toxicity of combination regimens. It remains possible that lower doses of combined gemcitabine, docetaxel, and pazopanib may be tolerable. However, caution should be exercised in future trials investigating similar combinations.

Background.

For extremity soft tissue sarcomas (STS), surgical resection remains the standard of care, and the addition of chemotherapy is controversial. This was a phase Ib/II trial of neoadjuvant therapy for patients with STS.

Methods.

Patients with high grade, extremity STS of >8 cm and amenable to definitive resection were treated with up to four 21-day cycles of 900 mg/m² gemcitabine on days 1 and 8, 75 mg/m² docetaxel on day 8, and 400 mg of pazopanib daily (GDP), followed by surgery and, if indicated, radiation therapy. Primary and secondary endpoints (phase Ib portion) were the safety and rate of pathologic response.

Results.

The trial was discontinued because of slow accrual after inclusion of five patients (leiomyosarcoma: two; undifferentiated pleomorphic sarcoma: three). Two patients completed four treatment cycles: one underwent surgery and one had insufficient response and received additional therapies. Three patients discontinued treatment because of toxicity. Grade 3 adverse events included hypertension, fatigue, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, hoarseness, and myelotoxicity. There were no complete or partial responses. One patient had ≥90% pathologic response. Among four patients who underwent resection, three remain free of disease, and one patient eventually relapsed.

Conclusion.

GDP combination used in the neoadjuvant setting resulted in significant toxicity; despite pathologic responses, no objective responses occurred.     

肢体软组织肉瘤709例外科治疗分析

目的探讨肢体软组织肉瘤(STS)的诊断与规范化的手术方式,以提高治疗效果。方法回顾性分析行手术治疗并经病理证实的709例肢体STS患者的临床资料。结果全组709例肢体STS患者中,术前行B超709例,CT 135例,MRI 587例。本组除216例行补充广泛切除术患者术前未再行术前活检,其余493例均进行术前活检,其中细针穿刺活检350例,粗针穿刺活检89例,切检54例。手术方式:434例行广泛切除术,125例行根治性间室切除术,113例行屏障切除术,37例行截肢术。术后病理检查结果显示,恶性纤维组织细胞瘤103例,滑膜肉瘤89例,脂肪肉瘤78例,横纹肌肉瘤74例,隆突性皮肤纤维肉瘤67例,纤维肉瘤62例,平滑肌肉瘤46例,腺泡状软组织肉瘤41例,透明细胞肉瘤36例,韧带样瘤型纤维瘤病31例,上皮样肉瘤29例,恶性神经鞘瘤27例,骨外尤文肉瘤11例,骨外骨肉瘤10例,血管肉瘤5例。531例术后随访0.3~4.5 a,73例复发(13.7%),复发时间11~32个月,中位复发时间为21个月。127例(23.9%)出现远处转移,其中86例为肺转移,31例为肝转移,10例为骨转移。结论 MRI或CT应为术前常规的辅助检查,活检有助于明确诊断,手术是肢体STS最重要的治疗手段,规范化的手术方式可以降低复发率。     

吉西他滨联合卡铂用于晚期鼻咽癌二线治疗的临床观察

 目的 观察吉西他滨（泽菲国产吉西他滨）联合卡铂的联合方案治疗晚期复治鼻咽癌的近期疗效及毒性反应。方法 32例均为一线含顺铂方案化疗失败的晚期鼻咽癌病人。吉西他滨1000mg／m²，d1.8；卡铂400mg／m²，d1；21天为1周期。完成2周期后评价疗效及毒性。结果 32例中CR4例，占12．5％；PR16例，占50．0％；总缓解率（CR＋PR）62．5％。SD8例（25％），PD4例（12．5％）。中位缓解时间4．5个月。骨髓抑制为主要毒性：Ⅲ／Ⅳ度白细胞下降为43．6％，4例合并感染发热；Ⅲ／Ⅳ度血小板下降为21．8％。胃肠道反应轻微。结论 吉西他滨与卡铂的联合方案对一线含顺铂方案化疗失败的晚期鼻咽癌有较高的缓解率，毒性反应轻，值得作为二线方案推广使用。     

Gemcitabine Plus Paclitaxel as Second-line Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival(PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastaticnon-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-linechemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine pluspaclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was asfollows: gemcitabine 1500 mg/m2 and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eightpatients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; medianage, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease(SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the medianPFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%),and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrileneutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion:The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-linechemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containingchemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, thisregimen was tolerated well by the patients.     

吉非替尼或多西紫杉醇二线治疗非小细胞肺癌临床研究

目的:观察吉非替尼（Iressa）与多西紫杉醇（艾素）单药二线治疗晚期非小细胞肺癌的疗效和不良反应。方法:98例经一线化疗失败的晚期非小细胞肺癌患者,随机分为吉非替尼组和多西紫杉醇组。吉非替尼组50例,口服 Iressa 250mg/次,1 次/天,直至疾病进展或出现不能耐受的不良反应;多西紫杉醇组 48例,应用艾素 75mg/m2,静脉滴注1h,第1 天,21天为1 个疗程,至少接受2 个疗程。按照RECIST实体瘤疗效评价标准进行疗效评价。结果:吉非替尼组（1 例服药1 个月后自动出组）有效率为22.4%（11/49）,临床获益率为55.1%（27/49）,中位生存时间为7.1 个月,1 年生存率为35.9% 。多西紫杉醇组有效率为18.8%（9/48）,临床获益率为50.0%（24/48）,中位生存时间为6.9 个月,1 年生存率为31.5% ,两组有效率、临床获益率、中位生存时间和1 年生存率差异均无统计学意义（P>0.05）。 吉非替尼组Ⅰ～Ⅳ度和Ⅲ～Ⅳ度皮疹发生率分别为51.0% 和10.2% ,明显高于多西紫杉醇组（P=0.000 0和P=0.029 6）,其Ⅰ～Ⅳ度腹泻发生率亦明显高于多西紫杉醇组（P<0.01）;而多西紫杉醇组患者白细胞减少发生率明显高于吉非替尼组（P=0.000 0）,血小板减少和贫血发生率仅Ⅰ～Ⅳ度高于吉非替尼组（P=0.000 0 和P=0.026 6）。生存质量改善率吉非替尼组高于多西紫杉醇组（P<0.01）。 结论:作为二线药物治疗晚期非小细胞肺癌,吉非替尼与多西紫杉醇相比,疗效相近,不良反应较轻,生存质量改善率更高,值得临床推广应用。      

Histology-Specific Therapy for Advanced Soft Tissue Sarcoma and Benign Connective Tissue Tumors

OPINION STATEMENT: Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.     

137 例MAID方案一线化疗转移软组织肉瘤的回顾性临床分析

目的：评价MAID方案一线治疗转移性STS 的临床疗效、不良反应和对生存期的影响。方法：根治术后出现远处转移的晚期STS 患者137 例,阿霉素（ADM）60mg/m2第1 天静脉滴注,异环磷酰胺（IFO ）8～10g/m2分4～5 天静脉滴注,IFO 开始静脉滴注的0、4、8h 各予美司纳（Mesna）每天总量的20% 静脉推注,氮烯咪胺（DTIC）200mg/m2静脉滴注,连续4～5 天。21天为1 个周期,完成2～6 个周期,中位周期数为4 个。结果：全组患者CR4 例（2.9%）,PR13例（9.5%）,SD88例（64.2%）,PD32例（23.4%）,有效率12.4% ,临床获益率76.6% 。PFS 2～14个月,mPFS（5.00± 1.12）个月,OS3～19个月,mOS（8.00± 1.32）个月。3 个月PFS 生存率56.9% ,6 个月PFS 生存率27.2% ,1 年PFS 生存率7.8% 。3 个月OS生存率100.0% ,6 个月OS生存率41.5% ,1 年OS生存率10.7% 。主要不良反应为骨髓抑制、胃肠道反应和脱发,其他不良反应少见。结论：MAID方案一线治疗转移性STS 疗效确切,能够有效控制疾病进展,不良反应可以耐受,作为进展期STS 的一线化疗方案具有明显的临床应用价值。