希罗达联合长春瑞宾二线治疗紫杉类及蒽环类失败复发转移性乳腺癌的疗效观察

目的观察希罗达联合长春瑞宾二线治疗复发转移乳腺癌的临床效果及不良反应发生情况。方法选择32例乳腺癌复发转移性患者,于第1、8天静脉滴注长春瑞宾25mg／m2;早晚2次口服希罗达2000mg／（m2·d）,连用2周,休息1周为1个周期。所有患者均行2个以上周期的治疗。结果32例患者中,5例完全缓解（CR）,12例部分缓解（PR）,11例病情稳定（SD）,4例病情进展（PD）,总有效率53．12％,临床获益患者（CR＋PR＋SD）28例（87．5％）。患者不良反应为恶心、呕吐、皮肤色素沉着、厌食、手足综合征和疲劳等,小部分患者有头晕、口腔炎、胸闷和腹泻发生,偶见谷丙转氨酶、胆红素轻度升高者,其中轻一中度白细胞下降及贫血者占36．4％。结论对紫杉类及蒽环类治疗失败的复发转移乳腺癌患者,希罗达联合长春瑞宾作为二线治疗方案治疗效果肯定,且不良反应轻,患者能耐受。     

国产长春瑞滨联合阿霉素治疗转移性乳腺癌的临床观察

目的：观察国产长春瑞滨（盖诺）联合阿霉素方案治疗转移性乳腺癌的临床疗效。方法：运用国产长春瑞滨（25mg/m^2 iv dl,5)加阿霉素（40mg/m^2iv dl)治疗转移性乳腺癌28例，结果：取得CR4例，PR13例，总有效率（CR＋PR）达60．7％；主要毒副反应为白细胞减少，发生率为92．8％，其中Ⅲ-Ⅳ度骨髓抑制占64．2％，结论：国产长春瑞滨加阿霉素方案对转移性乳腺癌疗效明确，血骨髓抑制明显。     

希罗达为主的联合方案治疗蒽环类耐药的复发转移性乳腺癌

目的 探讨希罗达为主的联合化疗方案治疗复发转移性乳腺癌的疗效及毒副反应.方法 42例复发转移性乳腺癌患者中,21例予以希罗达联合诺维本治疗;14例予以希罗达联合多西紫杉醇治疗;7例予以希罗达联合吉西他滨治疗.21 d为1周期,2周期后评价疗效.结果 41例可评价患者中,治疗后完全缓解(CR)8例,部分缓解(PR)16例,稳定(SD)9例,进展(PD)8例,有效率为58.54%.中位疾病进展时间为7.4个月,中位生存时间15.3个月.主要毒副反应为白细胞减少,其中Ⅲ～Ⅳ度占41.46%.结论 希罗达为主的联合化疗方案治疗复发转移性乳腺癌疗效确切,毒性反应可耐受.     

长春瑞滨联合希罗达治疗蒽环类和紫杉类耐药的晚期乳腺癌临床分析

  目的  观察长春瑞滨(NVB)联合希罗达(XEL)21天方案([NX]方案), 治疗蒽环类和紫杉类药物耐药的转移性乳腺癌(anthracycline-and taxanerefractory metastatic breast cance, ATRMBC)患者的疗效和不良反应  方法  NVB 25 mg/m 2d1, 8, 快速静滴; XEL2.0g/(m2·d), 早晚2次, 餐后30min口服, d1~14, 21天为1个疗程, 最多接受6个周期化疗或至疾病进展。  结果  48例患者共完成172个周期化疗, 中位化疗周期4个周期均可评价疗效和不良反应其中完全缓解(CR)0例, 部分缓解(PR)11例, 稳定(SD)23例, 进展(PD)14例总有效率(CR+PR)22.92%, 疾病控制率(DCR)70.83%, 中位无进展生存期(TTP)6.7个月(1~22个月), 1年生存率.32/48(66.70%), 2年生存率21/48(43.75%)。治疗后主要不良反应为血液学毒性及手足综合征, 其次为胃肠道反应及脉管炎。  结论  [NX]方案是治疗ATRMBC的有效方案, 不良反应可以耐受。      

长春瑞滨联合表阿霉素治疗转移性乳腺癌的临床观察

目的观察长春瑞滨（NVB）和表阿霉素（EPI）联合化疗方案在转移性乳腺癌治疗中的疗效和毒副反应。方法采用NVB25mg／m^2,第1、8天,EPI60mg／m^2第1天,每21天为一周期,共用2-4周期,随访6—36个月。结果18例24处转移灶中,完全缓解（CR）37．50％（9／24）,部分缓解（PR）16．67％（4／24）,疾病稳定（SD）37．50％（9／24）,SD≥6个月者20．83％（5／24）,疾病进展（PD）8．33％（2／24）。总有效率（CR＋PR）54．17％,临床获益率（CR＋PR＋SD≥6个月）为75．00％,中他疾病进展时间TTP为6．5个月。对锁骨上淋巴结转移的有效率最高达87．50％。不良反应主要为白细胞减少、脱发和周围静脉炎。Ⅲ-Ⅳ度白细胞减少发生率为72．22％,Ⅲ～Ⅳ度静脉炎的发生率为11．11％。结论,长春瑞滨联合表阿霉素在转移性乳腺癌治疗中疗效显著,不良反应可耐受。     

58含长春瑞滨方案治疗(蒽环类/紫杉类治疗后)复发转移乳腺癌的临床观察

目的:观察含长春瑞滨方案对蒽环类/紫杉类药物治疗后复发转移性乳腺癌的有效性和安全性.方法:蒽环类,紫杉类药物治疗后复发转移性乳腺癌患者61例,其中58例可评价疗效;长春瑞滨联合顺铂(NP)41例,长春瑞滨25mg/m2,第1天和第8天.静脉滴注;顺铂75～80mg/m2,静脉滴注,分割为2～5天,3周为一周期;长春瑞滨联合卡培他滨或替加氟(NF)17例,长春瑞滨用法同NP组,卡培他滨800～1 000mg/m2,分早晚两次服用,第1～14天,或替加氟600mg/m2,第2～6天,3周为一周期.化疗过程中注意观察不良反应,根据不良反应的程度调整药物用量.每两周期评价疗效.结果:长春瑞滨联合顺铂(NP)组,CR 2例(4.9%),PR 23例(56.1%),SD 14例(34.1%),PD2例(4.9%),有效率为61.0%;长春瑞滨联合卡培他滨或替加氟(NF)组,CR 1例(5.9%),PR 8例(47.1%),SD 7例(41.2%).PD 1例(5.9%),有效率52.9%.常见的不良反应主要为骨髓抑制、胃肠道反应、手足综合症、神经毒性等.结论:含长春瑞滨方案治疗蒽环类,紫杉类药物治疗后复发转移乳腺癌疗效确切,毒性可耐受,是治疗复发转移性乳腺癌的较好方案.     

长春瑞滨联合替吉奥治疗蒽环类和紫杉类耐药复发转移性乳腺癌的临床观察

目的观察长春瑞滨联合替吉奥治疗蒽环类和紫杉类耐药的复发转移性乳腺癌(anthracycline and taxaneresistant metaststic breast cancer,ATRMBC)的疗效和不良反应。方法 32例ATRMBC患者采用长春瑞滨(25 mg/m2静脉滴注,第1、8天)联合替吉奥(每天80 mg/m2,分2次口服,连服1～14天)治疗,3周为1个周期。治疗2个周期后按RE-CIST标准评价疗效及按WHO标准评价不良反应。结果 32例患者均可评价疗效和不良反应,其中完全缓解(CR)3例,部分缓解(PR)14例,稳定(SD)9例,进展(PD)6例。客观有效率(ORR=CR+PR)为53.1%,疾病控制率(DCR=CR+PR+SD)为81.3%。无进展生存期(progression-free survival,PFS)中位生存时间为8个月。主要不良反应为骨髓抑制及胃肠道反应,以Ⅰ、Ⅱ度为主,均可耐受。结论长春瑞滨联合替吉奥是治疗ATRMBC患者的有效方案,患者对不良反应能够耐受。     

58例含长春瑞滨方案治疗(蒽环类/紫杉类治疗后)复发转移乳腺癌的临床观察

目的：观察含长春瑞滨方案对蒽环类/紫杉类药物治疗后复发转移性乳腺癌的有效性和安全性。方法：蒽环类/紫杉类药物治疗后复发转移性乳腺癌患者61例,其中58例可评价疗效;长春瑞滨联合顺铂（NP）41例,长春瑞滨25mg/m^2,第1天和第8天,静脉滴注;顺铂75～80mg/m^2,静脉滴注,分割为2～5天,3周为一周期;长春瑞滨联合卡培他滨或替加氟（NF）17例,长春瑞滨用法同NP组,卡培他滨800～1000mg/m^2,分早晚两次服用,第1～14天,或替加氟600mg/m^2,第2～6天,3周为一周期。化疗过程中注意观察不良反应,根据不良反应的程度调整药物用量。每两周期评价疗效。结果：长春瑞滨联合顺铂（NP）组,CR2例（4.9%）,PR23例（56.1%）,SD14例（34.1%）,PD2例（4.9%）,有效率为61.0%;长春瑞滨联合卡培他滨或替加氟（NF）组,CR1例（5.9%）,PR8例（47.1%）,SD7例（41.2%）,PD1例（5.9%）,有效率52.9%。常见的不良反应主要为骨髓抑制、胃肠道反应、手足综合症、神经毒性等。结论：含长春瑞滨方案治疗蒽环类/紫杉类药物治疗后复发转移乳腺癌疗效确切,毒性可耐受,是治疗复发转移性乳腺癌的较好方案。     

多西紫杉醇联合长春瑞滨治疗蒽环类耐药性转移性乳腺癌的疗效分析

目的：观察多西紫杉醇、长春瑞滨联合方案在对蒽环类耐药转移性乳腺癌治疗中的疗效及不良反应。方法：蒽环类耐药性转移性乳腺癌35例，予多西紫杉醇联合长春瑞滨化疗，21天为1周期，至少用2周期。用世界卫生组织的疗效和抗肿瘤药急性及亚急性毒性反应分度标准评价疗效及毒性。结果：在35例可评价疗效的患者中，完全缓解10例，部分缓解13例，有效率为65．7％，临床获益率91．4％。不良反应主要骨髓抑制、脱发、消化道反应，但均可耐受，无化疗相关死亡。结论：该方案治疗蒽环类耐药性转移性乳腺癌患者，疗效较好，不良反应可耐受。     

长春瑞滨加顺铂方案治疗转移性乳腺癌

目的 研究长春瑞滨（NVB）和顺铂（PDD）联合化疗方案在转移性乳腺癌治疗中的疗效和毒副反应。方法 采用NVB 25mg／m^2,快速静滴,第1、8天,PDD 25mg／m^2,静滴,第1、2、3天,每3～4周为一周期,共用2～4周期,随访6～35个月。结果 26例中完全缓解（CR）7．69％（2／26）,部分缓解（PR）38．46％（10／26）,疾病稳定（SD）30．77％（8／26）,疾病进展（PD）23．08％（6／26）。总有效率（ORR为CR＋PR）46．15％,肿瘤控制率（CR＋PR＋SD）为76．92％,中位疾病进展时间TTP为6．5个月。其中对软组织、淋巴结转移疗效较好,对内脏、骨骼转移疗效较差。毒副反应主要为白细胞减少、胃肠道反应和周围静脉炎。Ⅲ～Ⅳ度白细胞减少发牛率为46．7％,Ⅲ～Ⅳ度静脉炎的发生率为7．69％。结论 长春瑞滨加顺铂方案在转移性乳腺癌治疗中疗效较好,毒副反应可耐受。     

去甲长春花碱联合顺铂治疗转移性乳腺癌

目的：观察去甲长春花碱（vinorelbine,NVB)联合顺铂（cisplatin,DDP)治疗转移性乳腺癌的疗效及不良反应,方法：采用NVB25mfg/m^2d1.8DDP30mg/m^2d1-3,每3周重复一次,共用2－4周期。结果：40例患者中有效率45％（18／40）,CR2．5％（1／40）,PR42．5％（17／40）,主要剂量限制不良反应是白细胞减少（Ⅲ、Ⅳ度27．5％）,结论：NVB联合DDP治疗转移性乳腺癌有较好的疗效,且阿霉素和／或泰素治疗失败的患者亦有较好的疗效,不良反应中耐受。     

Mitoxantrone Plus Vinorelbine in Pretreated Patients with Metastatic Breast Cancer

Abstract

Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC).

Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was ≤2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m², D1+8 and mitoxantrone 10 mg/m² D8 every 21 days for 6 cycles.

All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths.

The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.     

希罗达对晚期乳腺癌患者二线化疗临床研究

目的：评价希罗达对晚期乳腺癌患者二线化疗的有效率及耐受性,方法：开放性、多中心临床试验,入组病人接受希罗达单药2510mg.(m^2.d)^-1,分早期两次餐后口服治疗,连续14天,停药7天,共21天为一个疗程。结果：全组可评价疗效者67例,可评价不良反应者69例,其中CR4例（5．97％）,PR21例（31．34％）,总有效率3．71％,经4周年复查证实的ITT总有效率为32．86％,主要不良反应为手足综合症,皮肤色素沉症和腹泻,骨髓抑制相对较轻,白细胞下降发生率44．9％,除1例为Ⅳ级外,其余均为Ⅰ-Ⅱ级,结论：应用Xaloda二线治疗晚期乳腺癌与国外临床试验报告疗效相似或稍高,除少数患者发生严重不良反应外,多数病人耐受良好,希罗达可以治疗经阿霉素、紫杉醇等常规治疗失败的晚期乳腺癌。     

Phase I/II Trial of Vinorelbine and Sorafenib in Metastatic Breast Cancer

PurposeWe investigated the efficacy and toxicity of sorafenib, a multikinase inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in combination with vinorelbine therapy in a phase I/II trial in patients with metastatic breast cancer.Patients and MethodsWe enrolled 11 patients in the phase I portion to determine the maximum tolerated dose (MTD) of the combination, followed by 35 extra patients treated at the MTD in phase II. The median age of patients was 54 years old (range, 31-72 years old). Tumors were estrogen receptor and progesterone receptor (ER/PR) positive in 54% (22/54) of patients, and triple negative (ER⁻, PR⁻, HER2⁻) in 41% (17/54) of patients. Of all patients, 22% received sorafenib and vinorelbine as first-line therapy, 37% as second-line therapy, and 41% as third-line therapy.ResultsIn total, 41 patients were treated at the MTD (6 during phase I; 35 in phase II). The observed 44% 4-month progression-free survival rate was similar to the estimated historical rate of 43% with vinorelbine treatment. The combination was tolerated with expected toxicities. Patients treated at the MTD who had received prior bevacizumab treatment received a median of 1.5 cycles (range, 1-10 cycles) compared with a median of 5 cycles (range, 2-12 cycles) for patients without prior bevacizumab treatment.ConclusionFurther evaluation of vinorelbine and sorafenib in bevacizumab-naive patients may be of interest if specific biomarkers guiding patient selection can be identified.     

Phase I-II Vinorelbine (Navelbine®) by Continuous Infusion in Patients with Metastatic Breast Cancer: Cumulative Toxicities Limit Dose Escalation

Vinorelbine (Navelbine®) has significant activity against breast carcinoma and is less neurotoxic than vinblastine. Because vinblastine has improved activity when administered by continuous infusion, we conducted a Phase I-II study to determine the maximum tolerated dose (MTD) of vinorelbine when given by continuous infusion and the response rates to it in heavily pretreated metastatic breast cancer patients. Between April 1994 and August 1997, 87 patients were entered in the study. All were female and had proven metastatic breast cancer. Ninety-five percent of them had received prior doxorubicin treatment, and 74% had received prior paclitaxel treatment. In Phase I of the study, all patients received 8 mg of vinorelbine by intravenous (i.v.) bolus followed by a continuous infusion of vinorelbine over 96 hr. When the MTD was determined, patients were entered in the Phase II arm to assess treatment responses and cumulative toxic reactions. In the Phase I arm (43 patients, 182 cycles), we determined the MTD of vinorelbine to be 8 mg by i.v. bolus followed by a continuous infusion of 11 mg/m2/day over 4 days. The dose-limiting toxic reaction was grade 3-4 granulocytopenia in 35% of the cycles and neutropenic fever in 15% of the cycles. Forty-four patients (193 cycles) were treated at the MTD. Seven (16%) of them had a response (2 complete responses, 5 partial responses). The median durations of response and survival were 4.3 and 8.6 months, respectively. However, cumulative toxic reactions (neutropenic fever and stomatitis) in 22 patients (50%) required dose reductions. A continuous infusion of vinorelbine can be safely administered but with a narrow therapeutic index because of cumulative toxic reactions. We recommend a modified MTD of vinorelbine: 8 mg by i.v. bolus followed by a continuous infusion of 10 mg/m2/day over 4 days. However, this treatment schedule offers no apparent advantage over the commonly used weekly vinorelbine schedule.     

希罗达治疗晚期乳腺癌和结直肠癌24例

目的：探讨希罗达治疗晚期乳腺癌、结直肠癌的疗效及不良反应。方法：单药22例口服希罗达每日2500mg/m^2，分早晚各1次，连服14天，3周为一周期。联合治疗2例，口服希罗达每日1250mg/m^2，分早晚各1次，连服14天；奥沙利铂120mg/m^2第1天静脉点滴，3周为一周期，3周期后评价疗效。结果：20例可评价疗效：PR3例．有效率15％，其中乳腺癌1例，结直肠癌2例；SD12例占60％；PD5例占25％。肿瘤标记物(CEA)明显下降1例．治疗后生活质量明显提高2例。希罗达不良反应轻，主要为手足综合征，发生率为46％(11／24)，较有关报道为高．多为Ⅰ～Ⅱ度，均为可逆。结论：希罗达通过独特的酶激活途径在肿瘤组织内转化为抗肿瘤药5-FU，提高肿瘤组织内的药物浓度，提高细胞毒作用的选择性，口服给药方便简单，无需住院。对经阿霉素、紫杉醇治疗失败的乳腺癌及复发转移的结直肠癌患者均有一定疗效。且能提高生活质量，不良反应轻，适合老年及体弱多脏器病变患者服用。     

力尔凡联合长春瑞滨卡培他滨治疗晚期乳腺癌39例

目的:观察力尔凡联合长春瑞滨、卡培他滨方案治疗晚期乳腺癌的疗效及安全性。方法:39例有可测量病灶的转移性乳腺癌患者,按就诊先后顺序随机分为综合治疗组和对照组。对照组患者中心静脉持续滴注长春瑞滨,口服卡培他滨。综合治疗组在对照组用药的基础上加用力尔凡静脉滴注。结果:综合治疗组21例患者中CR2例(9.5%),PR6例(28.6%),MR4例(19.1%),总有效率为58.2%。对照组18例患者中,CR1例(5.6%),PR4例(22.2%),MR3例(16.6%),总有效率为44.4%。综合治疗组的有效率明显高于对照组,且不良反应的发生率低于对照组。结论:力尔凡联合长春瑞滨、卡培他滨治疗晚期乳腺癌,可以起到增效减毒作用,并且使长春瑞滨、卡培他滨作为二线方案治疗晚期乳腺癌,不良反应可以耐受。     

希罗达联合多西紫杉醇治疗晚期乳腺癌20例临床观察

目的观察以希罗达为主的联合多西紫杉醇治疗晚期乳腺癌的疗效及毒副反应。方法2004年1月至2006年1月对20例晚期乳腺癌患者,采用希罗达2500mg/m^2,每天分早晚2次餐后30min温开水送服,连用14天,停药7天。多西紫杉醇75mg/m^2加生理盐水100ml第1,8天静脉滴注,在接受多西紫杉醇治疗之前进行预处理,在用药前日晚21时及次日5时口服地塞米松7.5mg,连服3天,21天为1个周期。治疗2～4个周期后评价疗效及不良反应。结果20例患者中8例接受了2个周期化疗,12例完成4个周期的化疗。完全缓解（CR）,2例（10%）部分缓解（PR）,7例（35%）好转（MR）,4例（20%）稳定（SD）,2例（10%）进展（PD）,5例（25%）总有效率（RR）,（CR＋PR）45%。最常见的不良反应为胃肠道反应、骨髓抑制、手足综合症、皮肤色素沉着、少数乏力等。Ⅲ度不良反应仅见于少数病例,其中中性粒细胞减少5例、手足综合症2例。结论希罗达联合多西紫杉醇作为二线方案治疗晚期乳腺癌的疗效确切,显著延长疾病进展时间,提高生存率,而且不良反应轻,有望成为紫杉类或蒽环类药物治疗失败的晚期乳腺癌的理想方案。     

Eribulin Monotherapy in Patients Aged 70 Years and Older With Metastatic Breast Cancer

Purpose.

Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients.

Methods.

Data were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m² as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50–59 years, 60–69 years, ≥70 years).

Results.

Overall, 827 patients were included in the analysis (<50 years, n = 253; 50–59 years, n = 289; 60–69 years, n = 206; ≥70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia).

Conclusion.

Eribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups.