贝伐单抗联合白蛋白结合型紫杉醇治疗复发性卵巢癌的临床观察

目的 比较贝伐单抗联合白蛋白结合型紫杉醇与贝伐单抗治疗卵巢癌的疗效及不良反应.方法 60例经病理组织学和(或)细胞学检查确诊的ⅢB期或Ⅳ期复发型卵巢癌患者,其中多伐单抗联合白蛋白结合型紫杉醇组(联合组)28例,贝伐单抗组32例,分别给予贝伐单抗联合白蛋白结合型紫杉醇和贝伐单抗方案进行4个周期的治疗.评估两种治疗方法的近期疗效和不良反应.结果 联合组和贝伐单抗组的疾病控制率分别为85.7％和81.2％,部分缓解率分别为46.4％和43.7％.贝伐单抗组OS为7.0个月,联合组OS为7.3个月;P=0.63.贝伐单抗组与联合组中性粒细胞减少发生率分别为50.0％和42.8％,3～4级白细胞减少发生率分别为43.8％和24.9％ (P=0.001),两组比较差异具统计学意义,血小板减少发生率分别为53.0％和25.0％,差异具有统计学意义.结论 贝伐单抗联合白蛋白结合型紫杉醇治疗复发型卵巢癌疗效良好,不良反应少,安全性更好.     

贝伐珠单抗联合多西他赛治疗Her-2阴性复发转移性乳腺癌的疗效观察

背景与目的:贝伐珠单抗是首个抗血管生成的分子靶向药物,可以与多种化疗药物联合用于治疗复发转移性乳腺癌.本研究旨在观察贝伐珠单抗联合多西他赛治疗复发转移性乳腺癌的疗效和不良反应.方法:28例Her-2阴性的复发转移性乳腺癌患者均接受贝伐珠单抗联合多西他赛方案治疗,多西他赛75 mg/m2静滴,第1天:同时给予贝伐珠单抗15 mg/kg,第1天;21 d为1个周期.每个周期评价疗效同时记录不良反应.结果:27例患者可评价疗效和不良反应,其中CR 1例,PR 21例,有效率(CR+PR)为81.5%.粒细胞减少及白细胞减少是主要的不良反应,Ⅳ度粒细胞减少发生率为85.2%.研究中观察到高血压3例,静脉血栓1例,分级均为1级.蛋白尿12例,鼻衄15例,均为1～2级.结论:贝伐珠单抗联合多西他赛是治疗Her-2阴性的复发转移性乳腺癌患者的有效方案,其不良反应能够耐受.     

贝伐珠单抗联合紫杉类药物一线治疗局部复发或转移性乳腺癌患者的安全性及疗效

[目的]研究贝伐珠单抗联合紫杉类药物一线治疗Her-2阴性的局部复发或转移性乳腺癌患者的安全性和疗效。[方法]32例Her-2阴性的复发或转移性乳腺癌患者,一线接受贝伐珠单抗联合紫杉类方案的化疗,直至疾病进展或不良反应不能耐受或患者要求出组。研究者选择化疗方案：贝伐珠单抗15mg／kg静滴d1,多西他赛75mg／m^2,静滴d1,21d为一个周期;或贝伐珠单抗10mg／kg静滴d1,15紫杉醇80mg／m^2,静滴d1,8,15,为一个周期。每3个周期评价疗效。[结果]32例可评价疗效和副作用,PR16例,SD15例,PD1例,总有效率50％,中位TTP为7.25个月。3级以上不良反应为阴道出血、粒细胞下降以及腹泻。[结论]贝伐珠单抗联合紫杉类药物治疗晚期乳腺癌不良反应可以耐受,具有一定疗效。     

白蛋白结合型紫杉醇治疗紫杉类耐药转移性乳腺癌47例

摘 要：［目的］ 探讨白蛋白结合型紫杉醇在传统紫杉类治疗失败的转移性乳腺癌中的近期疗效及安全性。［方法］ 筛选47例传统紫杉类（紫杉醇、多西紫杉醇）治疗失败转移性乳腺癌患者,其中31例行白蛋白结合型紫杉醇单药化疗,12例行白蛋白结合型紫杉醇联合卡培他滨化疗,4例行白蛋白结合型紫杉醇联合曲妥珠单抗方案化疗,观察患者的近期疗效和不良反应。［结果］ 47例患者治疗有效率为14.89%,临床获益率为57.45%,中位PFS 3.9个月。患者主要不良反应为中性粒细胞减少及感觉神经毒性。［结论］ 白蛋白结合型紫杉醇对紫杉类治疗失败的转移性乳腺癌仍具有良好的疗效,不良反应可耐受。     

白蛋白结合型紫杉醇联合贝伐珠单抗治疗复发性卵巢癌的临床分析

目的:探讨白蛋白结合型紫杉醇联合贝伐珠单抗治疗复发性卵巢癌疗效、不良反应和生存情况。方法:选取经病理学诊断为卵巢上皮癌患者78例,既往使用过紫杉类、吉西他滨等药物治疗后进展,接受白蛋白结合型紫杉醇联合贝伐珠单抗方案治疗。具体方案:第1天接受白蛋白结合型紫杉醇260mg/m2、第2天接受贝伐珠单抗15mg/m2,21d为1个周期,每个周期评价不良反应,2个周期评价疗效。结果:78例患者均可进行疗效评价,无完全缓解病例,部分缓解9例,稳定42例,进展27例,有效率为11.5%（9/78）,临床获益率为65.4%(51/78)。主要不良反应为骨髓抑制、消化道反应、乏力、脱发、外周神经毒性、皮疹、高血压、肌肉酸痛,不良反应多为I级和II级毒性,患者对毒副作用均可耐受,未发生治疗相关性死亡。结论:白蛋白结合型紫杉醇联合贝伐珠单抗治疗复发性卵巢癌可获得较好的疗效,不良反应可以耐受。     

多西他赛联合贝伐珠单抗及其单药维持治疗转移性乳腺癌的临床观察

目的 探讨多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗转移性乳腺癌的疗效和安全性。方法 8例转移性乳腺癌患者均为女性,年龄34～62岁,中位年龄为53岁,均经改良根治术后病理组织学确诊,免疫组化检查HER-2为（-）或（+）。治疗方案：贝伐珠单抗15mg／kg d1,多西他赛 75mg／m2 d1,3周为1周期。治疗6个周期未出现病情进展者应用贝伐珠单抗（15mg/kg）单药维持治疗,每3周1次。结果 全组8例中获CR 1例,PR 3例,SD 4例。有效率（RR）为50％,疾病控制率（DCR）为100％。7例经联合治疗6～9个周期后用贝伐珠单抗维持治疗,维持治疗时间为2～31.3个月,中位维持治疗时间为15.3个月,中位无进展生存期为22.3个月。全组5例发生3、4级中性粒细胞减少,其中2例伴发热;5例患者出现指甲毒性,其中3例1、2级,2例3级。贝伐珠单抗应用4～36.5个月过程中,1例发生血栓3级,1例高血压2级,1例高血压3级,2例蛋白尿2级。结论 多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗HER 2阴性转移性乳腺癌的疗效好,毒副反应可耐受,值得临床进一步应用。     

FOLFIRI方案联合或不联合贝伐珠单抗治疗转移性GEP-NEC的疗效和安全性

目的 探讨FOLFIRI方案联合或不联合贝伐珠单抗治疗转移性胃肠胰神经内分泌癌(gastroentempancreatic neuroendocrine carcinoma,GEP-NEC)的疗效和安全性.方法 回顾性分析12例转移性GEP-NEC患者临床资料,采用FOLFIRI方案(伊立替康+亚叶酸钙+5-氟尿嘧啶)联合或不联合贝伐珠单抗治疗,收集疗效和不良反应相关数据.结果 12例患者中,6例(50.0％)为既往EP方案(依托泊苷+顺铂)治疗失败,2例(16.7％)为其他方案(1例吉西他滨+白蛋白紫杉醇,1例奥沙利铂+卡培他滨)治疗失败,另4例为一线治疗.12例疾病控制率为83.3％ (10/12),其中7例(58.3％)为部分缓解(partial response,PR),3例(25.0％)为疾病稳定(stable disease,SD),2例(16.7％)为疾病进展(progressive disease,PD).7例(58.3％)联合贝伐珠单抗治疗,其中4例(57.1％)PR,2例(28.6％)SD,1例(14.3％)PD.5例不联合贝伐珠单抗患者,其中3例(60.0％) PR,1例(20.0％)SD,1例(20.0％)PD.所有患者无进展生存时间为5.1月(3.8-6.4月).Ⅲ～Ⅳ度毒性反应发生率为25.0％ (3/12),且均为Ⅲ度粒细胞减少,其他的常见不良反应包括贫血、转氨酶升高、高血压和蛋白尿等,均为Ⅰ～Ⅱ度.结论 FOLFIRI方案联合或不联合贝伐珠单抗在转移性GEP-NEC患者中的缓解率良好且耐受性佳.     

白蛋白结合型紫杉醇治疗晚期复治乳腺癌的临床观察

[目的]回顾性观察以白蛋白结合型紫杉醇为主联合化疗治疗晚期复治乳腺癌的有效性和安全性。[方法]经病理组织学检查确诊的Ⅳ期乳腺癌患者23例,接受白蛋白结合型紫杉醇为主的联合化疗方案治疗。用药1个周期后评价不良反应,2个周期后方可评价疗效。[结果]23例可评价病例中,无1例获得CR,PR 7例,SD 13例,PD 3例,客观总有效（RR）率为30.4%;疾病控制（DCR）率为87.0%。中位疾病进展时间为5.3个月,1年生存率为73.9%。主要不良反应为骨髓抑制,其中Ⅲ~Ⅳ度粒细胞减少发生率为47.8%,Ⅲ~Ⅳ度血小板下降发生率为13.0%、Ⅲ度贫血发生率为21.7%;非血液学毒性轻微,可以耐受。[结论 ]白蛋白结合型紫杉醇联合化疗治疗晚期复治乳腺癌,疗效较好,不良反应可以耐受,可以考虑作为晚期复治乳腺癌的解救化疗方案。     

雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案治疗晚期结直肠癌的临床观察

目的 探讨含雷替曲塞／贝伐珠单抗的联合化疗方案在晚期结直肠癌二线及二线以上治疗中的疗效及安全性。方法 收集二线或二线以上治疗均采用含雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案共15例晚期结直肠癌患者的资料,所有方案均以2周为1周期,其中采用雷替曲塞+贝伐珠单抗方案2例,雷替曲塞+贝伐珠单抗+伊立替康方案9例,雷替曲塞+贝伐珠单抗+奥沙利铂方案4例。贝伐珠单抗5mg／kg 静滴,d1;雷替曲塞2mg／m2静滴15min,d2;伊立替康180mg／m2静滴1h,d2;奥沙利铂85mg／m2静滴2h,d2。结果 15例患者均可评价疗效。获PR 2例,SD 10例,PD 3例,有效率为13.3％,疾病控制率为800％;中位无疾病进展时间为5.1个月（95％CI：3.404～6.813个月）,中位OS为11.5个月（95％CI：8.985～13.930个月）。毒副反应主要包括食欲减退、恶心呕吐、疲乏、白细胞减少和血小板减少等,3～4级毒副反应以食欲减退、恶性呕吐、疲乏和血小板减少为主。结论 含雷替曲塞／贝伐珠单抗联合伊立替康或奥沙利铂方案在晚期结直肠癌二线及二线以上治疗中的疾病控制率高,毒副反应可耐受,可推荐为Ⅲ期临床研究方案以及二线或二线以上晚期结直肠癌的治疗方案。     

白蛋白结合型紫杉醇治疗晚期恶性肿瘤的临床观察

目的：观察白蛋白结合型紫杉醇治疗晚期恶性肿瘤的疗效及毒副作用.方法：对采用含白蛋白结合型紫杉醇方案化疗的晚期恶性肿瘤患者32例进行回顾性分析,每例患者接受1-6个周期化疗,中位化疗4个周期.每2个周期后按照RECIST实体瘤近期客观疗效评定标准进行疗效评价.观察疗效和不良反应.结果：30例可评价疗效,完全缓解（CR）1例,部分缓解（PR） 13例,稳定（SD）7例,疾病进展（PD）9例.客观有效率（RR=CR＋ PR）46.6％,临床获益率（CR＋PR ＋SD）为70.0％.不良反应主要为骨髓抑制、消化道反应、感觉神经毒性.结论：白蛋白结合型紫杉醇治疗晚期恶性肿瘤,疗效较好,毒副反应小,值得临床上进一步推广应用.     

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer.

PURPOSE: ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease. RESULTS: Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions. CONCLUSION: ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.     

A Phase II Neoadjuvant Trial of Sequential Nanoparticle Albumin-Bound Paclitaxel Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide in Locally Advanced Breast Cancer

BackgroundNeoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy.Patients and MethodsSixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2⁺) patients. Primary endpoint was pathologic complete response (pCR; CR) in breast. Secondary endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free survival, and overall survival.ResultsSixty-five patients received at least 1 dose of chemotherapy and were included in this analysis. Sixty-three patients completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2⁺ women received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2⁺ subset, the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC.ConclusionAlbumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials.     

白蛋白结合型紫杉醇治疗晚期难治性乳腺癌的疗效及安全性分析

背景与目的：白蛋白结合型紫杉醇通过将紫杉醇与人血白蛋白相结合新型制剂方式提高了紫杉醇的疗效,目前主要应用于疾病进展迅速或联合化疗后复发的晚期乳腺癌。本研究对白蛋白结合型紫杉醇治疗晚期难治性乳腺癌的疗效和安全性进行探讨。方法：收集2009年7月-2014年1月在北京大学肿瘤医院接受白蛋白结合型紫杉醇单药或联合方案化疗的患者的临床资料,筛选疾病进展迅速和多线治疗后患者,每2个周期评价疗效,每周期评价不良反应,随访患者生存情况。结果：共58例难治性晚期乳腺癌患者入组,均可评价疗效,67.2%(39/58)为三线以上化疗患者,32.8%(19/58)接受一、二线解救化疗的均为辅助化疗后1年内复发、疾病进展迅速的患者,58例中84.5%的患者伴有内脏转移,93.1%的患者既往使用过紫杉类药物。化疗的客观有效率为13.8%(8/58),临床控制率为60.3%(35/58),中位无疾病进展时间为4.0个月,总生存时间为10.1个月。其中23例三阴性乳腺癌患者的客观有效率为13.0%,临床控制率56.5%,中位无疾病进展时间为4.1个月,总生存时间为6.6个月。3～4度不良反应主要为血液学毒性,中性粒细胞减低的发生率34.5%(20/58),粒细胞缺乏性发热发生率5.2%(3/58),贫血12.1%(7/58),血小板减低6.9%(4/58)。结论：白蛋白结合型紫杉醇单药及联合方案是进展迅速或多线治疗失败的难治性晚期乳腺癌的一种治疗选择,对既往接受过紫杉类药物治疗和晚期三阴性乳腺癌也显示出一定疗效,且毒副作用可耐受。     

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

PURPOSE: ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. PATIENTS AND METHODS: Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225). RESULTS: ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. CONCLUSION: ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.     

Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy

In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients. Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m², day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2 cycles. Both of the two patients achieved remarkable response with Partial Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15 ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and 60% respectively). The results indicate that regimen of pembrolizumab combination with albumin-bound paclitaxel might produce response in patients with HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy.     

Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel With Carboplatin and Trastuzumab as First-line Therapy for Women With HER2-Overexpressing Metastatic Breast Cancer

PurposeThis multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC).Patients and MethodsWe treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m² and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6–8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles.ResultsThe overall response rate (ORR) was 62.5% (95% CI, 45.7%–79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%).ConclusionWeekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.     

吉西他滨联合顺铂一线或二线治疗晚期三阴性乳腺癌的临床观察

目的　观察吉西他滨联合顺铂一线或二线方案治疗晚期三阴性乳腺癌的近期疗效和毒副反应。方法　５４例晚期三阴性乳腺癌患者接受吉西他滨联合顺铂治疗,其中一线治疗４５例,二线９例,具体方案：吉西他滨１０００ｍｇ／ｍ^２ｄ_１、ｄ_８,顺铂２５ｍｇ／ｍ^２ｄ_１～ｄ_３,２１天为１周期。每２周期评价疗效,每周期进行安全性评估。结果　５４例患者中位治疗周期数为６周期（２～８周期）,获ＣＲ８例（１４.８％）,ＰＲ２４例（４４.４％）,ＳＤ１８例（３３.３％）,ＰＤ４例（７.４％）,总有效率（ＣＲ＋ＰＲ）为５９.２％。主要毒副反应为骨髓毒性和消化道反应,３～４级毒性分别为中性粒细胞减少４０.７％,血小板减少３５.２％,乏力１８.５％,食欲下降１４.８％,贫血１１.１％,恶心呕吐９.２％,外周神经毒性１.９％。结论　吉西他滨联合顺铂治疗晚期三阴性乳腺癌近期疗效好,毒副反应可以耐受,可推荐作为晚期三阴性乳腺癌的治疗选择。     

Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes

PURPOSE: Nanoparticle albumin-bound paclitaxel, a solvent-free, albumin-bound paclitaxel, demonstrated antitumor activity in patients with taxane-naive metastatic breast cancer (MBC). We examined albumin-bound paclitaxel (100 mg/m2 or 125 mg/m2 administered weekly) to determine the antitumor activity in patients with MBC whose disease progressed despite conventional taxane therapy. PATIENTS AND METHODS: Women with MBC that was previously treated with taxanes were eligible for participation. Taxane failure was defined as metastatic disease progression during taxane therapy or relapse within 12 months of adjuvant taxane therapy. Primary objectives were response rates (RRs) and the safety/tolerability of albumin-bound paclitaxel. RESULTS: Women were treated with albumin-bound paclitaxel 100 mg/m2 (n = 106) or 125 mg/m2 (n = 75) on days 1, 8, and 15 of a 28-day cycle. Response rates were 14% and 16% for the 100-mg/m2 and 125-mg/m2 cohorts, respectively; an additional 12% and 21% of patients, respectively, had stable disease (SD) > or = 16 weeks. Median progression-free survival times were 3 months at 100 mg/m2 and 3.5 months at 125 mg/m2; median survival times were 9.2 months and 9.1 months, respectively. Survival was similar for responding patients and those with SD. No severe hypersensitivity reactions were reported. Patients who developed treatment-limiting peripheral neuropathy typically could be restarted on a reduced dose of albumin-bound paclitaxel after a 1-2-week delay. Grade 4 neutropenia occurred in < 5% of patients. CONCLUSION: Albumin-bound paclitaxel 100 mg/m2 given weekly demonstrated the same antitumor activity as albumin-bound paclitaxel 125 mg/m2 weekly and a more favorable safety profile in patients with MBC that had progressed with previous taxane therapy. Survival of patients with SD > or = 16 weeks was similar to that of responders.     

Weekly paclitaxel therapy for metastatic breast cancer

We treated 12 patients with metastatic breast cancer with weekly paclitaxel therapy. Paclitaxel was administrated by 1 hour infusion at a dose of 80 mg/m2 after short premedication every week on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. All patients had received prior metastatic chemotherapy, and prior anthracycline therapy was done in 66.7% of the patients. Partial responses were observed in 66.7% of the patients and progressive disease in 33.3%. The response rate was 66.7%. Responses were observed in 62.5% of the patients with prior anthracycline therapy. Grade 3/4 leukopenia and neutropenia occurred in 25% of the patients, respectively, and no grade 3/4 peripheral neuropathy was observed. Dyspnea occurred in 25% of the patients and was grade 3 in 16.7%. Dyspnea is thought to be one of the adverse events requiring caution with weekly paclitaxel administration. Weekly paclitaxel therapy is effective and well tolerated in patients with metastatic breast cancer.     

Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m² was administered in a 1-h infusion on a weekly basis to 35 patients who may previously have received adjuvant chemotherapy (but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m² per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR+PR+SD_{≥24 weeks}) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 neurotoxicity. Thus, this study has shown that weekly paclitaxel as first-line therapy for metastatic or advanced breast cancer produces comparable response rates and less toxicity than when the drug is given every three weeks.