长春瑞滨联合吉西他滨治疗蒽环类和紫杉类药物耐药的转移性乳腺癌的临床疗效分析

目的:观察长春瑞滨(vinorelbine, NVB)联合吉西他滨(gemcitabine, GEM)治疗蒽环类和紫杉类药物耐药的转移性乳腺癌(anthracycline- and taxane-refractory metastatic breast cancer, ATRMBC)患者的疗效和不良反应.方法:采用 NVB联合GEM方案(GN方案)治疗41例ATRMBC患者,NVB 25 mg/m2 静脉推注,第1、8天;GEM 1 000 mg/m2 静脉滴注,第1、8天;21 d为1个周期,最多接受6个周期的化疗.结果:41例患者共完成159个周期的化疗,中位化疗周期为4个周期.完全缓解1例(2.4%),部分缓解14例(34.2%),稳定18例(43.9%),进展8例(19.5%);客观有效率36.6%(95%CI:21.9～51.3);平均随访16.4个月,中位疾病进展时间6.1个月,中位生存期16.2个月.结论:NVB联合GEM是治疗ATRMBC的有效方案,患者对不良反应能够耐受.     

吉西他滨联合卡培他滨治疗蒽环类与紫杉类耐药转移性乳腺癌的临床观察

为了探讨吉西他滨联合卡培他滨方案治疗蒽环类与紫杉类药物耐药的晚期转移性乳腺癌的近期疗效及不良反应,选取37例耐药的晚期乳腺癌患者,接受吉西他滨1 000 mg/m2,静脉滴入,d1、d8;卡培他滨950 mg/m2,2次/d,口服,d1～d14.每3周重复.2个周期化疗后,总有效率(CR+PR)为29.7%(11/37),疾病控制率(CR+PR+SD)为70.3%(26/37).中位进展时间为6.9个月,中位生存时间为15.5个月.最常见的毒性为骨髓抑制、手足综合征及胃肠道反应.初步研究结果提示,吉西他滨联合卡培他滨是治疗蒽环类和紫杉类耐药的晚期乳腺癌的有效方法,不良反应可以耐受.     

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌的临床观察

近年来,我国的乳腺癌发病率呈逐年上升趋势,已经成为肿瘤导致妇女死亡的最主要原因。晚期乳腺癌患者平均生存时间仅18～30个月,药物治疗是晚期乳腺癌治疗的主要手段。含蒽环类的联合化疗方案已广泛用于乳腺癌的一线治疗。此外,抗癌活性较高的紫杉类药物,近年也逐渐用于早期的辅助治疗。但临床上仍有20％-30％的乳腺癌患者对其发生耐药,对于这类患者目前尚无公认的标准替代方案。     

卡培他滨联合多西紫杉醇治疗蒽环类耐药的转移性乳腺癌31例

为了探讨卡培他滨联合多西紫杉醇(DTX)治疗蒽环类耐药的转移性乳腺癌的疗效及不良反应,将61例确诊蒽环类耐药的转移性乳腺癌分为两组,联合组31例卡培他滨1650mg/(m2·d),口服,d1~d14;DTX75mg/(m2·d),静脉滴入,d1。对照组30例DTX100mg/(m2·d),静脉滴入,d1。两组每3周为1个周期,连用4个周期,治疗结束2周后评价疗效。61例均可评价疗效,联合组有效率(CR PR)为45·2%(14/31),中位生存时间为14·3个月。Ⅱ~Ⅲ度反应占67·7%(21/31),Ⅳ度反应占29·0%(9/31),主要为手足综合征、骨髓抑制、脱发和消化道毒性。对照组有效率(CR PR)为30·0%(9/30),中位生存时间为10·9个月。Ⅱ~Ⅲ度反应占50·0%(15/30),Ⅳ度反应占33·3%(10/30),主要为发热、肌痛、关节痛、嗜中性粒细胞减少症。初步研究结果提示,卡培他滨联合DTX对经吡柔比星治疗失败的乳腺癌较DTX单药有优势,且不良反应可以耐受。     

吉西他滨联合紫杉醇治疗晚期乳腺癌20例

目的观察吉西他滨联合紫杉醇治疗晚期乳腺癌的近期疗效和患者不良反应。方法吉西他滨1000mg／m^2静脉滴注第1,8天（第1天在紫杉醇之后用）,紫杉醇150～175mg／m^2静脉滴注第1天（GT方案）,21d为1个周期,治疗2个周期后评价疗效,有效者化疗4～6个周期。结果全组20例,CR0例,PR11例,SD5例,PD4例,总有效率55．0％。不良反应主要为Ⅰ～Ⅲ度白细胞及血小板减少、皮疹、脱发、轻度消化道反应及肌肉关节酸痛。结论吉西他滨联合紫杉醇治疗晚期乳腺癌疗效较好,不良反应可耐受,有较好的临床应用价值。     

吉西他滨联合顺铂治疗耐药转移性乳腺癌的临床观察

观察吉西他滨联合顺铂(DDP)方案治疗蒽环类和(或)紫杉类耐药转移性乳腺癌的疗效和不良反应.采用吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药转移性乳腺癌患者52例.吉西他滨1 000 mg/m2,静脉滴入,d1,d8;DDP 25 mg/m2,静脉滴入,d1～d3.21 d为1个周期,至少用2个周期.本组患者治疗有效率为44.2%(23/52),中位生存时间11.0个月,中位疾病进展时间为5.3个月,1年生存率为42.3%.主要不良反应为胃肠道反应和骨髓抑制.Ⅲ～Ⅳ度呕吐发生率为28.9%(15/52).Ⅲ～Ⅳ度中性粒细胞减少发生率为15.4%(8/52),Ⅲ～Ⅳ度血小板减少发生率为17.3%(9/52).初步研究结果显示,吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药的转移性乳腺癌疗效较好,毒副反应可耐受,是蒽环类及紫杉类耐药的转移性乳腺癌的有效选择.     

健择联合卡培他滨治疗晚期乳腺癌55例临床观察

为观察及评价盐酸吉西他滨(健择)联合卡培他滨(希罗达)治疗复发转移性乳腺癌的疗效和不良反应,武汉钢铁集团公司第二职工医院肿瘤中心对55例晚期乳腺癌患者均给予健择1000mg/m2,静脉滴入,d1、d8;希罗达口服,2次/d,餐后服用,每次1000mg/m2,连续服用14d;治疗周期为21d,至少治疗2个周期。结果完全缓解(CR)7例,部分缓解(PR)30例,稳定(SD)15例,疾病进展(PD)3例,总有效率67.3%,中位TTP6.5个月。不同转移部位或器官的有效率分别为:胸壁83.3%(15/18),淋巴结80.0%(20/25),肺脏75.0%(15/20),骨骼41.7%(5/12),肝脏28.0%(7/25)。Ⅰ、Ⅱ级不良反应为皮肤色素沉着40例,手足综合征35例,恶心呕吐30例,腹泻25例,白细胞下降40例,Ⅲ、Ⅳ级不良反应为白细胞下降7例,恶心呕吐3例,贫血3例。初步观察结果提示,健择联合希罗达治疗晚期乳腺癌疗效肯定,患者耐受性良好。     

吉西他滨联合长春瑞滨治疗蒽环类／紫杉类耐药晚期乳腺癌24例

[目的]观察国产吉西他滨联合长春瑞滨方案治疗蒽环类和／或紫杉类治疗失败的晚期乳腺癌的近期疗效与毒副反应。[方法]对接受蒽环类和,或紫杉类药物治疗病情进展的24例乳腺癌患者,采用国产吉西他滨联合长春瑞滨方案治疗：吉西他滨1000mg／m^2,静脉滴注30min,d1、d8;长春瑞滨25mg／m^2,静脉推注,d1、d8;每21d重复一次．至少2个周期评价疗效。[结果]全组24例患者均可评价疗效,其中CR2例（8.33％）,PR9例（37.50％）,SD8例（33．33％）。PD5例（20．83％）;客观有效率（CR＋PR）45．83％,临床受益率（CR＋PR＋SD）79．16％;中位疾病进展时间（TTP）6．8个月;中位生存期（MST）17．1个月。主要毒副反应为骨髓抑制和胃肠道反应,但均可耐受。[结论]吉西他滨联合长春瑞滨方案治疗蒽环类和／或紫杉类药物治疗失败的晚期乳腺癌患者,疗效确切,其毒副作用患者可以耐受．值得临床进一步研究.     

卡培他滨联合多西紫杉醇治疗转移性乳腺癌30例

 目的　探讨卡培他滨联合多西紫杉醇治疗转移性乳腺癌的疗效及患者的不良反应。方法　收集30例多柔比星或紫杉醇耐药的转移性乳腺癌患者，应用卡培他滨联合多西紫杉醇，卡培他滨2.0 g／m2，2次／d口服，第1天至第14天；多西紫杉醇35 mg／m2，第1、8、15天，21 d为1个周期，应用多西紫杉醇前用地塞米松8 mg口服3～4 d防止过敏反应，2个周期为一个疗程，用药 2个疗程以上评价疗效。结果　完全缓解（CR）2例，部分缓解（PR）13例，稳定（SD）8例，进展（PD）3例，有效率为57.6 %，临床获益率为88.4 %，主要不良反应为白细胞减少、脱发、恶心呕吐、口腔炎、腹泻、肝功能损害、手足综合征、心脏毒性及变态反应等。结论　对于蒽环类药物和（或）紫杉醇治疗无效的转移性乳腺癌患者，卡培他滨联合多西紫杉醇是一种新的可选择方案，值得临床应用。     

吉西他滨联合顺铂对蒽环类及紫杉类耐药的晚期乳腺癌的治疗

[目的]观察吉西他滨联合顺铂治疗耐蒽环类及紫杉类晚期乳腺癌的疗效及毒性反应。[方法]34例对蒽环类及紫杉类耐药的晚期乳腺癌患者，接受吉西他滨1000mg／m^2，静脉滴注，第1、8天；顺铂30mg／m^2，静脉滴注，第1～3天；21天为1个周期。[结果]全组病例共完成116个周期，巾位周期数为4个；1例（2．94％）完全缓解，15例（44．12％）部分缓解，12例（35．92％）病灶稳定，6例（17．85％）病灶进展，总有效率为47．10％。中位疾病进展时间为6个月．中位生存期为12．5个月；主要毒副反应为骨髓抑制及胃肠道反应。[结论]吉两他滨联合顺铂治疗耐蒽环类及紫杉类的晚期乳腺癌疗效较好，毒副反应较轻，可作为蒽环类及紫杉类治疗失败的晚期乳腺癌的解救方案。     

Second line chemotherapy with 5 fluorouracil and vinorelbine in anthracycline and taxane pretreated patients with metastatic breast cancer

Purpose. 5-Fluorouracil (5-FU) and Vinorelbine (Vin) are active in the second line therapy of metastatic breast cancer (MBC). We conducted a multi-institutional phase II study to assess the activity of the combination of 5-FU and Vin in anthracycline and taxane pretreated patients with MBC. Patients and Methods. Patients with MBC previously treated with anthracyclines and taxanes, who had measurable or evaluable disease, were treated with folinic acid 200 mg/m² IV, 5-FU 400 mg/m² IV bolus, and 5-FU 600 mg/m² continuous infusion over 24 hours on days 1, 2, 15, and 16 and Vin 25 mg/m² on days 1 and 15 of a 28-day cycle, for six cycles. Response rate, time to disease progression, overall survival, and toxicity were evaluated. Results. Thirty-eight patients were enrolled and 35 were evaluable for response. Grade III and IV neutropenia was seen in four and three patients, respectively. At a median follow-up of 19.5 months, 33 patients have progressed, 14 during treatment and 19 during the follow-up period, and 23 have died for an overall survival of 12.3 months. The time to progression was six months. Eight patients had a partial response and 14 had stable disease for a clinical benefit rate of 63%. Conclusion. The combination of 5-FU and Vin is well tolerated and is a good option for the palliative care of patients with MBC.     

吉西他滨联合顺铂治疗耐药三阴性晚期乳腺癌的临床观察

目的　观察吉西他滨联合顺铂方案治疗ＥＲ、ＰＲ、ＨＥＲ-２均阴性对蒽环类耐药的晚期转移性乳腺癌的疗效和安全性。方法　３４例对蒽环或紫杉类耐药晚期转移性乳腺癌患者,经免疫组化证实ＥＲ、ＰＲ、ＨＥＲ-２均阴性,给予吉西他滨联合顺铂方案治疗,具体用药为：吉西他滨１０００ｍｇ／ｍ^２静脉滴注,第１,８天;顺铂２５ｍｇ／ｍ^２静脉滴注,第１～３天。２１天为１周期,至少２个周期,２周期后评价疗效和毒副反应。结果　３４例患者均可评价疗效,获完全缓解（ＣＲ）２例（５.９％）,部分缓解（ＰＲ）１２例（３５.３％）,稳定（ＳＤ）１４例（４１.２％）,进展（ＰＤ）６例（１７.６％）,总有效率（ＣＲ＋ＰＲ）为４１.２％;中位疾病进展时间为５.２个月。主要不良反应包括骨髓抑制和胃肠道反应,无化疗相关死亡。结论　吉西他滨联合顺铂方案对蒽环类或紫杉类耐药的转移性三阴性乳腺癌有较好的近期疗效,不良反应可耐受,是有效的解救方案之一。     

吉西他滨联合顺铂方案治疗耐药晚期乳腺癌

目的：对蒽环类和紫杉类药物耐药的晚期乳腺癌患者，使用吉西他滨联合顺铂方案化疗的疗效及毒性评估。方法：耐药的晚期乳腺癌患者，接受吉西他滨1．0g／m^2，静脉滴注，第1、8天；顺铂25mg／m^2，静脉滴注，第1～3天；每21天重复1疗程，至少应用2疗程，然后评价临床疗效和毒性，并进行随访。结果：30例患者进入研究，均可评价疗效和毒副反应，中位疗程数为3(2～4)。5例(16．7％)获得完全缓解，10例(33．3％)获得部分缓解，13例(43．3％)病灶稳定，2例(6．7％)病灶进展，总有效率50．0％；化疗毒性主要表现为骨髓抑制和胃肠道反应，Ⅲ—Ⅳ度毒性发生率为50％。中位随访12．5(2～48)月，中位无进展生存期为10个月，中位生存期为14个月。结论：对于蒽环和紫杉醇耐药的复发或晚期乳腺癌，吉西他滨联合顺铂是治疗耐药晚期乳腺癌的有效方案，毒性可被耐受。     

Gemcitabine/anthracycline combinations in metastatic breast cancer

Gemcitabine has demonstrated single-agent efficacy in the treatment of advanced breast cancer, with response rates of up to 42%. The agent is well tolerated, with relatively mild side effects, and has limited overlapping toxicities with other drugs used in combination chemotherapy for breast cancer. It is, therefore, a good candidate for inclusion in multidrug regimens for the treatment of this disease. This article reviews results of gemcitabine/anthracycline-containing double- and triple-drug combinations used to treat patients with early-stage and advanced breast cancer. Results from phase I and II trials were promising, with good tolerability and overall response rates ranging from 33%-89% in advanced disease and up to 95% in the neoadjuvant treatment of early-stage disease. A phase III trial is currently comparing gemcitabine/epirubicin/paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide in patients with advanced breast cancer. Preliminary toxicity data on 78 patients show that both regimens were well tolerated, with similar incidences of treatment-related effects. Additional comparative studies of gemcitabine-containing drug regimens in breast cancer are warranted.     

长春瑞滨联合顺铂治疗对蒽环类及紫杉类耐药乳腺癌的疗效观察

目的:观察长春瑞滨联合顺铂方案治疗蒽环类及紫杉类耐药转移性乳腺癌的疗效和不良反应.方法:长春瑞滨联合顺铂方案治疗蒽环类及紫杉类耐药转移性乳腺癌38例.长春瑞滨25mg/m2静脉滴注,第1、8天,顺铂70mg/m2分4次静脉滴注,第1-4天.21天为1个周期,至少应用2个周期.结果:本组患者治疗有效率36.8%(14/38),中位生存时间15.6(95%CI 12.8-17.2)个月,中位疾病进展时间6.2个月,1年生存率68.4%.无化疗相关死亡,主要不良反应为骨髓抑制及胃肠道反应.结论:长春瑞滨联合顺铂方案对蒽环类及紫杉类耐药的转移性乳腺癌有较好的近期疗效,不良反应可耐受,为有效的解救方案.     

Phase II gemcitabine and capecitabine combination therapy in recurrent or metastatic breast cancer patients pretreated with anthracycline and taxane

Purpose

We conducted a phase II study evaluating safety and efficacy of combination gemcitabine and capecitabine therapy for metastatic breast cancer patients following anthracycline and taxane treatment in Korea.

Methods

This was a single-arm, non-randomized phase II study. Patients received 1,000 mg/m² gemcitabine intravenously over 30 min on days 1 and 8, and 1,250 mg/m² capecitabine orally twice daily on days 1–14 until disease progression or intolerable toxicity occurred. This regimen was repeated every 3 weeks. The primary outcome assessed was overall response rate [ORR, complete response (CR) + partial response (PR) as the best response], and secondary outcomes were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) [maintenance of CR + PR + stable disease (SD) for at least 3 months], drug toxicity, and predictive factors for response to this regimen.

Results

Of 41 patients, the ORR was 39.0 % (CR 0 %; PR 39.0 %), and DCR was 78.0 % using this chemotherapy. DCR for 6 and 12 months was 68.3 and 26.8 %, respectively. Median PFS was 10.0 months [95 % confidence interval (CI) 7.8–12.1], and median OS was 25.1 months (95 % CI 18.2–32.1). Prominent toxicities were neutropenia and hand–foot syndrome. Most adverse events were well known, relatively moderate, and reversible. Taxane sensitivity [odds ratio (OR) 0.169; 95 % CI 0.034–0.826; P = 0.028] and hepatic metastasis (OR 0.097; 95 % CI 0.017–0.559; P = 0.009) were significantly predictive of response to gemcitabine and capecitabine combination.

Conclusions

This study showed reproducible anticancer activity and tolerable toxicity of gemcitabine and capecitabine combination therapy in recurrent or metastatic Korean breast cancer patients previously treated with anthracycline and taxane.     

长春瑞滨联合顺铂治疗对蒽环类及紫杉类耐药乳腺癌的疗效观察

目的：观察长春瑞滨联合顺铂方案治疗蒽环类及紫杉类耐药转移性乳腺癌的疗效和不良反应.方法：长春瑞滨联合顺铂方案治疗蒽环类及紫杉类耐药转移性乳腺癌38例.长春瑞滨25mg/m2静脉滴注,第1、8天,顺铂70mg/m2分4次静脉滴注,第1-4天.21天为1个周期,至少应用2个周期.结果：本组患者治疗有效率36.8%（14/38）,中位生存时间15.6（95%CI 12.8-17.2）个月,中位疾病进展时间6.2个月,1年生存率68.4%.无化疗相关死亡,主要不良反应为骨髓抑制及胃肠道反应.结论：长春瑞滨联合顺铂方案对蒽环类及紫杉类耐药的转移性乳腺癌有较好的近期疗效,不良反应可耐受,为有效的解救方案.     

Ixabepilone plus capecitabine for Chinese patients with metastatic breast cancer progressing after anthracycline and taxane treatment

Purpose

Effective treatment options for patients with metastatic breast cancer pretreated with or resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of ixabepilone plus capecitabine in both anthracycline-pretreated and resistant and taxane-resistant metastatic breast cancer of Chinese women.

Patients and methods

Patients with measurable disease who had anthracycline and taxanes as prior neoadjuvant, adjuvant or metastatic therapy were treated with ixabepilone at 40 mg/m² intravenously on day 1 of 21-day cycle plus capecitabine 2,000 mg/m² orally on day 1 through 14 of a 21-day cycle. The primary end point was the objective response rate. The secondary end points were time to progression, overall survival, and toxicity profiles.

Results

Twenty-one patients received 146 cycles with a median of 5 cycles (range 1–13 cycles) per patients. Fourteen patients (66.7%) had partial response, 5 patients (23.8%) had stable disease, and 2 patients (9.5%) had progressive disease. Median time to progression and duration of response were 6.2 and 6.0 months, respectively. The median overall survival was 16.7 months. Eight (38.1%) patients required dose reduction and 14 (66.7%) patients discontinued treatment for adverse effect. Grade 3/4 treatment-related events included fatigue (28.6%), peripheral sensory neuropathy (33.3%), neutropenia (61.9%), anemia (4.7%), hypokalemia (4.7%), hand and foot syndrome (19.0%) and infection (9.5%). Resolution of grade 3/4 peripheral neuropathy was reversible after a median period of 6 weeks.

Conclusion

Ixabepilone plus capecitabine demonstrated a clear activity and an acceptable safety profile in Chinese patients with anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer, and the majority of patients completed 6 cycles of the therapy with manageable neuropathy toxicities.