NCb与NX方案治疗蒽环及紫杉类耐药的乳腺癌的临床研究

目的：观察长春瑞滨联合卡铂与长春瑞滨联合卡培他滨（Xeloda）对紫杉类及蒽环类耐药的晚期乳腺癌的疗效及不良反应。方法：80例确诊为紫杉类、蒽环类耐药的晚期乳腺癌患者随机分为A、B两组,各40例,A组：长春瑞滨25mg／m2,静滴,d1,8,卡培他滨1650mg／m2,口服,d1-14;B组：长春瑞滨25mg／m2,静滴,d1,5,卡铂350mg／m2,静滴,d1;3周1个周期,平均4周期,化疗结束2—3周后评价疗效。结果：78例患者可评价疗效,A组有效率37．5％,1年生存率42．5％,中位进展时间4．6个月;B组有效率42．1％,1年生存率45％,中位进展时间3．4个月,两组各指标差异无显著性（P〉0．05）。A组患者的手足综合症发生率明显高于B组（P〈0．05）;B组患者的呕吐、白细胞及血小板减少发生率明显高于A组（P〈0．05）,但Ⅲ-Ⅳ度呕吐、白细胞及血小板减少的发生率无明显升高（P〉0．05）。结论：对于紫杉类、蒽环类耐药的晚期乳腺癌患者,长春瑞滨联合卡铂是一个安全、有效、经济的化疗方案。     

GP方案与NP方案治疗蒽环类及紫杉类耐药晚期乳腺癌的疗效观察

目的:观察吉西他滨联合顺铂(GP方案)与长春瑞滨联合顺铂(NP方案)治疗蒽环类及紫杉类治疗失败的晚期乳腺癌的近期疗效及不良反应。方法:将接受蒽环类及紫杉类药物治疗失败的45例晚期乳腺癌患者随机分组,GP方案组22例,NP方案组23例,化疗2周期后评价疗效。结果:GP组与NP组总有效率分别为40.9%和43.5%,疾病控制率分别为72.7%与69.6%,1年生存率分别为54.5%与52.2%,两组比较差异无显著性(P>0.05)。主要不良反应为骨髓抑制及消化道反应,两组比较差异无显著性(P>0.05)。结论:GP方案与NP方案治疗蒽环类及紫杉类耐药的晚期乳腺癌近期疗效肯定,不良反应可耐受。     

吉西他滨联合卡铂治疗蒽环及紫杉类治疗失败的晚期乳腺癌的临床观察

目的:探讨吉西他滨联合卡铂方案治疗蒽环及紫杉类治疗失败的晚期乳腺癌的疗效和不良反应.方法:将56例蒽环、紫杉类治疗失败的晚期乳腺癌患者随机分为观察组(30例)和对照组(26例).观察组采用吉西他滨联合卡铂方案治疗,对照组采取CAF治疗方案.结果:治疗有效率观察组和对照组分别为73.33％和46.15％,观察组疗效显著优于对照组;不良反应的发生率两组之间没有明显差异.GC组及CAF组的中位肿瘤进展时间(TTP)分别为7.5个月和4.5个月,中位生存期分别为8.3个月和6.5个月,均无显著性差异(P＞0.05).结论:吉西他滨联合卡铂治疗蒽环及紫杉类治疗失败的晚期乳腺癌,具有很好的疗效和较低的毒副作用.     

含长春瑞滨方案治疗晚期乳腺癌的临床观察

目的观察和比较长春瑞滨为基础的两组联合化疗方案二线治疗蒽环和紫杉类药物耐药的晚期乳腺癌的有效率、中位疾病进展时间（mTTP）和不良反应,同时探讨联合化疗对老年乳腺癌的作用及安全性。方法对蒽环类和紫杉类药物失败的晚期乳腺癌患者53例采用长春瑞滨联合顺铂（NP）或联合卡培他滨（NX）方案治疗,其中有8例为老年乳腺癌（≥70岁）,采用NX方案。结果 NP组23例,CR2例（8.7%）,PR10例（43.5%）,总有效率为52.2%,mTTP为8个月（95%CI为6.16～8.80个月）。NX组（〈70岁）22例,CR2例（9.1%）,PR12例（54.5%）,总有效率为63.6%,mTTP为8.5个月（95%CI为6.71～9.29个月）。两组有效率差异无显著性（P=0.436）。8例老年乳腺癌（≥70岁）中,CR1例,PR3例,SD2例,PD2例,mTTP为6.5个月（95%CI为3.16～12.09个月）。两种化疗方案不良反应主要有骨髓抑制及消化道反应,在〈70岁患者中NX方案恶心呕吐发生率较NP方案低,差异有显著性（P=0.04）。NX方案还可见皮肤色素沉着及手足综合征。结论含长春瑞滨方案对蒽环类和紫杉类药物失败的晚期乳腺癌均有较好的疗效,但NX方案消化道反应发生率较低。NX方案对于老年晚期乳腺癌治疗具有一定的疗效和安全性。     

长春瑞滨联合顺铂治疗蒽环及紫杉类耐药的晚期乳腺癌的疗效观察

目的探讨长春瑞滨联合顺铂方案治疗蒽环及紫杉类耐药晚期乳腺癌的疗效。方法将60例蒽环及紫杉类耐药的晚期乳腺癌患者随机分为观察组(30例)和对照组(30例)。观察组采用长春瑞滨联合顺铂方案治疗,对照组采取经典CAF治疗方案。结果治疗有效率观察组为60.00%,对照组为30.00%,观察组疗效显著优于对照组;不良反应的发生率2组之间没有明显差异。结论长春瑞滨联合顺铂治疗蒽环及紫杉类耐药的晚期乳腺癌,具有很好的疗效和较低的毒副作用。     

NP方案与GX方案二线治疗晚期乳腺癌的临床对比观察

 目的　比较长春瑞滨联合顺铂（NP）方案和吉西他滨联合卡培他滨（GX）方案二线治疗蒽环类和（或）紫杉类耐药晚期乳腺癌患者的疗效和不良反应。方法　75例晚期乳腺癌患者被抽信封法随机分为2组,其中NP组40例,GX组35例。NP方案：长春瑞滨25 mg／m2,静脉滴注,第1、8天;顺铂25 mg／m2,静脉滴注,第1天至第3天;21 d为1个周期。GX方案：吉西他滨1000 mg／m2,静脉滴注,第1、8天;卡培他滨2500 mg／m2,分2次口服,第1天至第14天;21 d为1个周期,2个周期后评价疗效和不良反应。结果　NP组和GX组总有效率分别为42.5 ％（17／40）和40.0 %（14／35）,中位疾病进展时间分别为7.0和6.5个月,中位生存期分别为15.8和15.0个月,1、2年生存率分别为60.0 %、32.5 %和57.1 %、31.4 %,Karnofsky评分提高率分别为50.0 %（20／40）和42.9 %（15／35）。以上差异均无统计学意义（均P＞0.05）。2组主要不良反应为骨髓抑制、消化道反应,其中GX组的手足综合征发生率明显高于NP组[29 %（10／35）比0],消化道反应NP组明显高于GX组[95 %（38／40）比26 %（9／35）],差异均有统计学意义（均P＜0.05）。结论　NP方案与GX方案对晚期乳腺癌患者有较好疗效,且不良反应均可耐受,可作为蒽环类、紫杉类药物治疗失败的晚期乳腺癌患者解救方案。     

GP与NP方案治疗耐药晚期乳腺癌的临床观察

目的 比较吉西他滨联合顺铂(GP方案)和长春瑞滨联合顺铂(NP方案)治疗蒽环和(或)紫杉类耐药转移性乳腺癌的近期疗效和安全性。方法 采用GP方案(吉西他滨+顺铂)36例,吉西他滨1000mg/m²静脉滴注,第1,8天给药;顺铂75mg/m²分3次静脉滴注,第1-3天给予。采用NP方案(长春瑞滨+顺铂)32例,长春瑞滨25mg/m²,第1,8天给予;顺铂用法同A组。两方案均每3周重复,2个周期以上评价疗效。结果 两组有效率分别为55.6%(20/36)和53.1%(17/32),无统计学意义(χ²=0.0403,P=0.84)。GP组III-IV度血小板减少高于NP组,但NP组静脉炎相对较明显。结论 GP与NP方案治疗蒽环类和(或)紫杉类耐药的晚期乳腺癌有较高的有效率,可指导临床,且不良反应均可以耐受。     

长春瑞滨联合卡培他滨或替吉奥治疗紫杉类及蒽环类耐药晚期乳腺癌的效果分析

目的 比较长春瑞滨（NVB）联合卡培他滨（XLD）或替吉奥（S-1）治疗蒽环类及紫杉类耐药的晚期乳腺癌患者的临床疗效及不良反应。方法 收集2012年6月至2014年6月于本院肿瘤内科住院的对紫杉类及蒽环类耐药的晚期乳腺癌患者64例,其中33例患者接受NVB联合XLD方案（NX组）,31例患者接受NVB联合S-1方案（NS组）。NX组具体方案为：NVB 25 mg／m2静脉滴注,d1、d8;XLD 2000 mg／m2,分2次口服,d1～d14。NS组的具体方案为：NVB 25 mg／m2静脉滴注,d1、d8;S 1 40 mg（体表面积≤125 m2）、50 mg（125 m2＜体表面积＜15 m2）或60 mg（体表面积≥1.5 m2）,口服,每日2次,d1～d14。两组均21天为1周期。2个周期后采用实体瘤疗效评价标准（RECIST）1.1版评价近期疗效,采用美国国立癌症研究所毒性判定标准（NCI-CTCAE）4.0评价毒性反应,同时随访患者的生存情况。结果 全组64例患者均可评价疗效,其中NX组33例患者中获CR 3例,PR 13例,SD 12例,PD 5例,有效率（RR）和疾病控制率（DCR）分别为485％和848％;NS组31例患者中获CR 3例,PR 13例,SD 8例,PD 7例,RR和DCR分别为516％和774％。两组RR和DCR的差异无统计学意义（P＞005）。NX组的中位无进展生存期为7.8个月,与NS组的7.2个月比较,差异无统计学意义（P＞0.05）。两组的主要不良反应为骨髓抑制和消化道反应,以1～2级为主,均可耐受。NX组手足综合征的发生率高于NS组（45.5％ vs. 16.1％）,差异有统计学意义（P＜0.05）。结论 NVB联合XLD或S-1治疗蒽环类及紫杉类耐药的晚期乳腺癌的疗效相当,毒副反应较轻且均可耐受,NVB联合S-1的手足综合征发生率较低,两种方案均值得临床推广。     

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.     

长春瑞滨联合卡培他滨治疗晚期乳腺癌的临床研究

目的观察长春瑞滨（vinorelbine,NVB）联合卡培他滨（capecitabine,CAPE）对蒽环和（或）紫杉类耐药的晚期乳腺癌的疗效及毒性。方法蒽环和（或）紫杉类耐药晚期乳腺癌患者29例,给予长春瑞滨25mg／m2,第1、8d,采用PICC管静脉滴注;卡培他滨每天1000mg／m2,每天2次,餐后30rain用温水送服,连用14d,休息7d,21d为1个周期。2个周期后评价疗效,有效者化疗4个周期以上。随访6—30个月。结果29例患者共化疗124个周期,化疗周期中位数为4个周期（2—10个周期）,完全缓解（CR）1例,部分缓解（PR）13例,占44．8％,稳定（SD）10例,占34．5％,进展（PD）5例,占17．2％。有效率（CR＋PR）达48．3％。中位疾病进展时间（TTP）为5．2个月,中位总生存期（OS）为18．2个月。常见不良反应为骨髓抑制、胃肠道反应和手足综合征等。结论长春瑞滨联合卡培他滨对紫杉类或蒽环类耐药的晚期乳腺癌有较好的疗效,毒性可以耐受。     

卡培他滨联合长春瑞滨治疗晚期乳腺癌临床观察

目的：观察卡培他滨联合长春瑞滨对耐药的晚期乳腺癌的疗效及毒性。方法：34例耐药的晚期乳腺癌,均接受卡培他滨2500mg／m^2,分早晚两次餐后30分钟温开水送服,第1—14天,间隔7天;长春瑞滨25mg／m^2加入生理盐水100ml中静脉滴注15分钟,第1、8天,21天为1周期,化疗4个周期。结果：34例患者中,CR5例（14．71％）,PR15例（44．12％）,SD8例（23．51％）,PD6例（17．65％）,有效率为58．82％,疾病控制率为82．35％。结论：卡培他滨联合长春瑞滨治疗耐药的晚期乳腺癌有较好的疗效,不良反应轻,患者可耐受。     

卡培他滨联合长春瑞滨治疗晚期乳腺癌临床观察

目的:观察卡培他滨联合长春瑞滨对耐药的晚期乳腺癌的疗效及毒性.方法:34 例耐药的晚期乳腺癌,均接受卡培他滨 2500 mg/m2,分早晚两次餐后30分钟温开水送服,第1-14天,间隔7天;长春瑞滨 25mg/m2 加入生理盐水100ml中静脉滴注15分钟,第1、8天,21天为1周期,化疗4个周期.结果:34例患者中,CR 5例(14.71%),PR 15例(44.12%),SD 8例(23.51%),PD 6例(17.65%),有效率为58.82%,疾病控制率为82.35%.结论:卡培他滨联合长春瑞滨治疗耐药的晚期乳腺癌有较好的疗效,不良反应轻,患者可耐受.     

长春瑞滨单药周疗方案治疗既往应用过蒽环类和紫杉类药物的晚期乳腺癌临床观察

目的 观察长春瑞滨(NVB)单药治疗对既往应用过蒽环类和/或紫杉类药物的转移性乳腺癌的疗效和安全性.方法 我院从2008年1月至2011年7月共有31例既往应用过蒽环类和/或紫杉类药物的转移性乳腺癌患接受了NVB单药周疗方案治疗.结果 全组化疗共113个周期,中位化疗周期数为4个(2～6个周期).完全缓解(CR)1例(3%),部分缓解(PR)7例(22%),稳定(SD)4例(13%),进展(PD)19例(61%),总有效率(RR＝CR+PR)为26%,临床获益率(CR+PR+SD＞6个月)为32%,中位疾病进展时间(TTP)4.0个月,中位生存期为13个月.主要不良反应为骨髓抑制及胃肠道反应,无化疗相关死亡病例.结论 长春瑞滨单药治疗既往应用过蒽环类和/或紫杉类药物的转移性乳腺癌有一定疗效,且耐受性好.     

Late phase II clinical study of vinorelbine monotherapy in advanced or recurrent breast cancer previously treated with anthracyclines and taxanes

BACKGROUND: At present, it is one of the most important issues for the treatment of breast cancer to develop the standard therapy for patients previously treated with anthracyclines and taxanes. With the objective of determining the usefulness of vinorelbine monotherapy in patients with advanced or recurrent breast cancer after standard therapy, we evaluated the efficacy and safety of vinorelbine in patients previously treated with anthracyclines and taxanes. METHODS: Vinorelbine was administered at a dose level of 25 mg/m(2) intravenously on days 1 and 8 of a 3 week cycle. Patients were given three or more cycles in the absence of tumor progression. A maximum of nine cycles were administered. RESULTS: The response rate in 50 evaluable patients was 20.0% (10 out of 50; 95% confidence interval, 10.0-33.7%). Responders plus those who had minor response (MR) or no change (NC) accounted for 58.0% [10 partial responses (PRs) + one MR + 18 NCs out of 50]. The Kaplan-Meier estimate (50% point) of time to progression (TTP) was 115.0 days. The response rate in the visceral organs was 17.3% (nine PRs out of 52). The major toxicity was myelosuppression, which was reversible and did not require discontinuation of treatment. CONCLUSION: The results of this study show that vinorelbine monotherapy is useful in patients with advanced or recurrent breast cancer previously exposed to both anthracyclines and taxanes.     

Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer

Background: Capecitabine and i.v. vinorelbine are both active in metastatic breast cancer with non‐overlapping toxicities. This study examined the efficacy and safety of the combination of these agents in patients with pretreated metastatic breast cancer. Methods: Patients previously treated for breast cancer, maximum of one prior metastatic regimen, received capecitabine 1000 mg/m² b.d. for days 1–14 and vinorelbine 25 mg/m² i.v. days 1 and 8 every 21 days. All patients had measurable disease and adequate baseline organ function. The primary endpoint was response and secondary endpoints time to progression, duration of response, survival and safety. Results: Twenty‐two patients (median age 56 years) received a median of six cycles. All patients had received anthracyclines and 64% taxanes. Objective responses were seen in 7/21 (33%, 95% confidence interval [CI] 18–57%), with two complete responses; stable disease was seen in 5/21 (24%, 95% CI 8–42%). Median duration of response was 6.9 months (95% CI 4.7–13.1), time to progression was 5.8 months (95% CI 2.8–6.8) and survival was 13.5 months (95% CI 6.9–19.9). The median dose intensity of vinorelbine was 75% of the intended dose and of capecitabine 85% of intended dose. The main toxicity was myelosuppression including 16 episodes of G3–4 neutropenia in 11 patients (50%). Other toxicities were generally mild to moderate. Conclusion: The combination of capecitabine and i.v. vinorelbine is active and well tolerated in patients with pretreated metastatic breast cancer. The recent availability of oral vinorelbine provides an opportunity to explore a fully oral combination.     

吉西他滨联合卡培他滨治疗耐药性乳腺癌近期疗效观察

目的：对蒽环类和（或）紫杉类耐药性乳腺癌尚无标准解救方案.本研究探讨既往接受过蒽环类和或紫杉类药物治疗失败的晚期乳腺癌患者,使用吉西他滨联合卡培他滨方案治疗的疗效和不良反应.方法：23例患者入选,均给予吉西他滨1000mg/m2,静脉滴注,第1、8天;卡培他滨2000mg/m2,分2次口服,第1-14天;每3周为1周期,至少应用2周期,评价临床疗效和不良反应,并进行随访.结果：23例患者中完全缓解1例,部分缓解11例,总有效率52.2%.主要不良反应为骨髓毒性及手足综合症,均较轻.结论：吉西他滨联合卡培他滨方案治疗蒽环类和（或）紫杉类耐药晚期乳腺癌有较好的近期疗效,不良反应小,值得临床选择应用.     

Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer

Background:

An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.

Methods:

Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m⁻² plus vinorelbin 25 mg m⁻² on days 1+8 (GemVin), or plus cisplatin 30 mg m⁻² on days 1+8 (GemCis), or plus capecitabine 650 mg m⁻² b.i.d. orally days 1–14 (GemCap), q3w. The primary end point was response rate.

Results:

A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ⩾grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand–foot syndrome in 2.0% of the GemCap patients (per patient analysis).

Conclusions:

This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.     

Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer.

PURPOSE: To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLT) of the combination of capecitabine and vinorelbine in patients with metastatic breast cancer who relapse after adjuvant and/or first-line treatment. In addition, we aimed to obtain data on efficacy and safety at the recommended dose. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer after failure of prior chemotherapy (including anthracyclines and/or taxanes) were eligible. Capecitabine was administered with a fixed dose of 1000 mg/m(2) orally twice daily for 2 weeks followed by 1 week rest. One treatment cycle consisted of 6 weeks of treatment containing two treatment periods of capecitabine. Vinorelbine was given intravenously at escalated doses of 25 mg/m(2) (dose level 1) and 30 mg/m(2) (dose level 2) on days 1 and 8, and 22 and 29. RESULTS: Thirty-three patients received a total of 91 cycles of capecitabine and vinorelbine. The median number of administered cycles per patient was three (range one to six). Thirty-one patients were evaluable for toxicity. At dose level 2 four out of seven patients experienced DLTs (nausea/vomiting, febrile neutropenia, grade 4 neutropenia, infection and diarrhea); thus, the MTD was defined. In order to confirm the safety and efficacy, dose level 1 was extended to 24 patients. Two patients [8.3%; 95% confidence interval (CI) 1% to 27%] showed DLTs (hospitalization due to febrile neutropenia and prolonged neutropenia). The main toxicity was neutropenia, which was observed at National Cancer Institute Common Toxicity Criteria grade 3 and 4 in 39% of patients. The overall response rate for capecitabine and vinorelbine was 55% (95% CI 36% to 72.7%), including three patients with a complete remission. The median time to disease progression was 8 months (95% CI 4.3-11.7) with an overall survival of 19.2 months (95% CI 11.3-27.1) based on intention-to-treat analysis. CONCLUSIONS: The combination of capecitabine and vinorelbine can be administered with manageable toxicity and showed significant efficacy for patients with metastatic breast cancer even after failure of a anthracycline- and/or taxane-based therapy.