吉西他滨联合长春瑞滨治疗晚期三阴性乳腺癌的临床观察

目的：观察吉西他滨联合长春瑞滨（ＧＮ方案）治疗ＥＲ、ＰＲ、ＨＥＲ ２均阴性（三阴性）晚期转移性乳腺癌的疗效与安全性。方法：２００４年１月～２００８年１月共３７例经免疫组化证实ＥＲ、ＰＲ、ＨＥＲ ２均阴性的晚期转移性乳腺癌复治患者参与研究。患者接受吉西他滨联合长春瑞滨方案治疗：吉西他滨１ ０００ｍｇ／ｍ２,静脉滴注３０ｍｉｎ,ｄ_１、ｄ_８;长春瑞滨２５ｍｇ／ｍ^２静脉滴注１５ｍｉｎ,ｄ_１、ｄ_８。２１天重复。结果：全组３７例共完成１３６个周期的治疗,中位数４个周期,范围２～６个周期,均可评价疗效。完全缓解１例（２.７％）,部分缓解８例（２１.６％）,病情稳定２０例（５１.４％）,病情进展９例（２１.６％）,客观有效率为２４.３％;中位疾病进展时间（ｍＴＴＰ）６个月（９５％ ＣＩ：４～８个月）,中位生存期（ＯＳ）２４个月（９５％ ＣＩ：１１～３７个月）,１年生存率为（６６.２４±８.４３）％,３年生存率为（２８.７７±１１.９６）％。毒副反应主要为Ⅰ ～Ⅱ度骨髓抑制、末梢神经毒性、胃肠道反应、流感样症状、轻度肝功能损伤等。结论：吉西他滨联合长春瑞滨治疗晚期三阴性乳腺癌患者,初步观察有一定的疗效,其毒副作用患者可以耐受。     

长春瑞滨联合吉西他滨治疗晚期乳腺癌21例临床观察

乳腺癌是危害女性健康的主要恶性肿瘤,全世界每年约有120万妇女发生乳腺癌,有50万妇女死于乳腺癌,乳腺癌在我国的发病率更是呈逐年上升趋势,术后5年大约30％发生肿瘤的复发和转移。我们于2003年5月～2005年5月应用长春瑞滨（NVB）＋吉西他滨（GEM）联合治疗对紫杉类和／或蒽环类耐药的乳腺癌患者21例取得较好疗效,现报告如下：     

长春瑞滨或吉西他滨联合顺铂治疗耐药的晚期乳腺癌

乳腺癌是妇女常见的恶性肿瘤,含蒽环类和紫杉类药物的化疗方案广泛应用于乳腺癌的一线治疗,但对上述药物治疗后出现的复发、转移尚无公认的标准替代方案。如何治疗该类药物化疗失败的晚期乳腺癌患者成为临床医师面临的难题。从2002年2月～2007年3月,我们应用国产长春瑞滨与吉西他滨分别联合顺铂方案,治疗既往经蒽环类和／或紫杉类化疗后转移的乳腺癌患者66例,观察其近期疗效及不良反应,现报告如下。     

吉西他滨联合长春瑞滨治疗蒽环类和紫杉类耐药的晚期乳腺癌的临床观察

目的:观察吉西他滨联合长春瑞滨治疗蒽环类和紫杉类耐药的晚期乳腺癌的临床疗效及毒副反应。方法:45例晚期乳腺癌患者,应用吉西他滨1000mg/m2静脉滴注第1、8天,长春瑞滨25mg/m2静脉滴注第1、8天,每21天重复。治疗2个周期评价疗效,每周期评价毒副反应。结果:45例患者均可评价疗效。获CR 1例,PR 13例,总有效率(CR+PR)为31.1%。所有患者中位疾病进展时间为5.7个月,中位生存时间为15.3个月。主要毒副反应为骨髓抑制,出现Ⅲ/Ⅳ度中性粒细胞减少8例(17.8%),Ⅲ/Ⅳ度血小板减少4例(8.9%),无治疗相关性死亡。结论:吉西他滨联合长春瑞滨治疗蒽环类和紫杉类耐药的晚期乳腺癌疗效较好,毒副反应可以耐受,值得临床进一步研究。     

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.     

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。     

吉西他滨和长春瑞滨联合治疗之后序贯吉西他滨或长春瑞滨治疗晚期耐药性乳腺癌的临床疗效

目的吉西他滨和长春瑞滨（GN）方案治疗晚期紫杉类及蒽环类药物耐药型乳腺癌中的作用已得到验证,但对于晚期乳腺癌化疗的疗程,是联合或单药,尚无标准方案,比较GN方案8疗程与GN方案4疗程后序贯G或N 4疗程,对蒽环类及紫杉类均耐药转移性乳腺癌（MBC）的疗效及不良反应。方法选取2008年1月至2009年12月确诊的晚期乳腺癌患者60人,所有患者均已接受过蒽环类和紫杉类方案化疗,采用GN方案8疗程或GN方案4疗程序贯G或N方案化疗,比较患者的总有效率（ORR）及1年生存率。结果 GN 8疗程组ORR为35.5%（11/30）,其中CR 6.5%（2/31）,PR 29%（9/31）;GN方案4疗程序贯G或N治疗组ORR为34.5%（10/29）,其中CR6.9%（2/29）,PR 27.6%（8/29）。两组ORR差异无统计学意义（P=0.935）。GN方案8疗程组1年生存率为67.7%;GN方案4疗程序贯G或N治疗组1年生存率为65.5%,两组1年生存率（P=0.586）差异无统计学意义。两组均无化疗相关死亡病例,主要不良反应为骨髓抑制及胃肠道反应。结论 GN方案8疗程与GN方案4疗程序贯G或N治疗方案对蒽环类及紫杉类均耐药MBC均有较好的缓解率,不良反应均可耐受,同为有效解救方案。但从药物经济学上讲,GN×4-G or N更符合晚期患者治疗原则。     

长春瑞滨联合顺铂治疗晚期乳腺癌42例临床观察

目的观察抗肿瘤药长春瑞滨联合顺铂治疗晚期乳腺癌的疗效。方法符合入组条件的晚期乳腺癌42例,长春瑞滨(NVB)25mg/m2,第1￣8天联合顺铂(DDP)30mg/m2,第1￣3天,化疗3周期。结果RR24例(57.1%),CR2例(4.8%),PR22例(52.3%)。主要毒副作用为骨髓抑制、胃肠道反应。白细胞减少的发生率95.2%,其中Ⅲ￣Ⅳ度者7.1%。恶心、呕吐的发生率92.9%,无Ⅲ￣Ⅳ度者。结论长春瑞滨联合顺铂方案是一个既有效毒性又相对小的选择。     

洛铂联合长春瑞滨治疗46例晚期乳腺癌的临床观察

目的：观察长春瑞滨（NVB）联合洛铂（LBP）的NL方案治疗晚期乳腺癌的近期疗效和不良反应。方法：从2009年2月至2011年6月,采用NVB加LBP的联合化疗方案治疗晚期乳腺癌46例,LBP 30mg/m2,第1天,静脉滴注3小时;NVB 25mg/m2,第1、8天,静脉滴注30分钟,21天为1周期。结果：46例患者中,CR 2例,PR 16例,SD 17例,PD 11例,RR为39.1%,DCR（CR＋PR＋SD）为76.1%。主要不良反应为骨髓抑制,白细胞下降（Ⅲ＋Ⅳ度）发生率45.7%,血小板下降（Ⅲ＋Ⅳ度）发生率8.7%。,非血液学毒性轻微,可以耐受。结论：LBP联合NVB治疗晚期乳腺癌疗效较好,不良反应可以耐受,可以作为晚期乳腺癌的二线治疗方案或解救方案。     

长春瑞滨联合顺铂治疗晚期乳腺癌

我院2000年5月～2001年6月应用国产长春瑞滨联合顺铂方案治疗乳腺癌患22例，取得了一定的疗效，现报告如下：     

Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer

The aim of this study was to evaluate the safety and efficacy of combined treatment with trastuzumab (T), gemcitabine (gem) and vinorelbine (vin) as second-line therapy for HER-2 overexpressing metastatic breast cancer, pretreated with anthracyclines and/or taxanes and/or trastuzumab. Eligible patients had HER-2/neu-positive disease (IHC 2+ or 3+), performance status (PS) or=2 metastatic sites. Of the patients, 7 (23.3%) had received trastuzumab as first-line therapy. Treatment was well-tolerated with grade 4 neutropenia in 6 patients, grade 3 thrombocytopenia and grade 3 anemia in 1 patient, and grade 3 asthenia in 4 patients. Fifteen patients obtained an objective response (response rate, 50%; C.I. 95%, range, 31.3-68.7%). Among the patients with HER-2/neu 3+, the response rate was 73.3%. Noteworthy were 4 objective responses observed in patients with brain metastasis. Also, 7 patients had stable disease (23.3%). Median progression-free survival was 7 months (range 5-10), and median overall survival was 15 months (range 5-33). T-gem-vin is a safe and active regimen in this subgroup of patients with poor prognosis, and the efficacy of such a schedule was particularly satisfactory in patients with HercepTest 3+.     

Phase I/II study of gemcitabine in association with vinorelbine for metastatic breast cancer

Background. Gemcitabine (G) and vinorelbine (V) have favorable safety profile and antitumor activity in metastatic breast cancer. To exploit their different mechanism of action and lack of overlapping toxicity, we performed a phase I and II study of G and V in combination. Patients and methods. Fifty-three patients with metastatic breast cancer were treated. In the dose-finding phase, seven cohorts of patients (22 women) received increasing doses to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination. Patients recruited in the phase II portion of the study (31 women) received the dose level immediately below the one defined as MTD (i.e., G 1200mg/m², V 30mg/m², on day 1 and day 8, every 3 weeks). Results. Dose escalation was discontinued at G 1400mg/m² and V 30mg/m² because of toxic death due to thrombocytopenia and CNS hemorrage. No other limiting toxicities were observed, and tolerability was similar at all dose levels studied in the escalation portion of the study. The main toxicity was granulocytopenia of grade 3/4 in 36 and 48% of the patients on phase I and II respectively, without episodes of neutropenic fever. Thrombocytopenia was uncommon. Other side effects were usually mild to moderate. In 46 evaluable patients, the response rate was 24% (complete response 7%, partial response 17%). Disease stabilization was observed in further 17%. The median duration of response was 12 months (range 5–14) and the median survival was 20 months (range 1 to 45+). Conclusions. G and V, on day 1 and 8 of 3-weekly cycles, can safely be administered to patients with metastatic breast cancer at the dose of 1200 and 30mg/m², respectively. The antitumor activity of G and V in combination was similar to that reported when using either drug as single agent.     

吉西他滨联合顺铂治疗晚期三阴乳腺癌的疗效观察

目的 评价吉西他滨联合顺铂（GP方案）治疗晚期三阴乳腺癌（triple negative breast cancer,TNBC）的疗效和不良反应。方法 回顾性分析晚期TNBC患者37例,采用顺铂（DDP） 25 mg/m²静脉滴注,d1~d3;吉西他滨（GEM）1 000 mg/m²静脉滴注,d1、d8;21 d为1个周期,分析临床疗效和不良反应。结果 完全缓解（CR）1例、部分缓解（PR）16例、疾病稳定（SD）12例、疾病进展（PD）8例,治疗有效率（RR）为45.9％。中位无进展生存时间（PFS）为5.5个月,中位总生存时间（OS）为15.5个月,主要不良反应为骨髓抑制和消化道反应。结论 GP方案治疗晚期TNBC疗效确切,耐受性较好,可作为解救方案。     

Clinical study of gemcitabine therapy for recurrent or metastatic pancreatic cancer

The clinical efficacy and safety of gemcitabine (GEM) monotherapy were studied retrospectively in the patients with recurrent or metastatic pancreatic cancer. The subjects were 30 patients who were treated with GEM at our center between May 2001 and August 2003. The objective overall response rate was 11% (3/28; 95% confidence interval, 2.3-28%). The disease control rate (CR+PR+SD) was 54%. Grade 3 or 4 neutropenia was most frequently seen in 46%. Non-hematological toxicities were mild. The median survival time was 4.8 months. One-year survival rate was 15%. This study showed the reproducible activity and safety of GEM in practice.     

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.     

曲妥珠单抗联合吉西他滨治疗ＨＥＲ２阳性的转移性乳腺癌

目的：探讨曲妥珠单抗（赫赛汀）联合吉西他滨（ＧＥＭ）治疗表皮生长因子受体２（ＨＥＲ２）阳性的转移性乳腺癌（ＭＢＣ）的疗效和不良反应。方法：ＨＥＲ２阳性的ＭＢＣ女性患者９例,给予ＧＥＭ１０００ｍｇ／ｍ^２,静脉滴注,ｄ１、ｄ８、ｄ１５,４周重复;赫赛汀静脉滴注,首次４ｍｇ／ｋｇ,其后每周１次,２ｍｇ／ｋｇ,连续使用。结果：９例患者中,ＣＲ１例（１１.１％）,ＰＲ６例（６６.７％）,ＳＤ和ＰＤ各１例（１１.１％）,有效率（ＲＲ）为７７.８％,疾病控制率（ＤＣＲ）为８８.９％;中位肿瘤进展时间（ＴＴＰ）为１８个月,中位总生存时间（ＯＳ）为２３个月。主要毒性反应是骨髓抑制和消化道反应,且均为Ⅰ ～Ⅱ度。结论：赫赛汀联合吉西他滨对于难治性转移性乳腺癌是有效且安全的治疗方案。     

Carboplatin in combination therapy for metastatic breast cancer

BACKGROUND: Anthracycline-based regimens have a limited role in patients with metastatic breast cancer due to cumulative cardiotoxicity and their common use in adjuvant chemotherapy. New nonanthracycline regimens are, therefore, needed for metastatic disease. Single-agent carboplatin is active in patients with previously untreated metastatic breast cancer, producing response rates of 20%-35%. Preclinical studies have demonstrated synergistic antitumor efficacy of carboplatin and trastuzumab in HER2(+) models. METHODS: Phase II and III clinical trial data of combination therapy with carboplatin (Paraplatin; Bristol-Myers Squibb; Princeton, NJ), a taxane, and/or trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) in metastatic breast cancer were identified from multiple sources, including: A) clinical trial data published in peer-reviewed journals within the last 5 years; B) preliminary clinical trial data from abstracts recently presented at national meetings; and C) phase III protocols currently evaluating carboplatin-based combination regimens. RESULTS: In several phase II studies, combination carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb) therapy was active and reasonably well tolerated in the first-line treatment of metastatic breast cancer, producing objective response rates of 53%-62%-substantially higher rates than those seen in other phase II trials of either drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere; Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior efficacy than paclitaxel/trastuzumab alone for patients with HER2(+) metastatic disease. Drug scheduling plays an important role in the therapeutic ratio of this combination treatment. CONCLUSIONS: Incorporation of carboplatin as a standard agent in first-line treatment of metastatic breast cancer has support from several recent studies. Preliminary results of combination carboplatin/taxane therapy with trastuzumab in metastatic disease are encouraging, and other carboplatin combinations are also being investigated in other phase II and III trials in patients selected based on the HER2 status of their cancer. Results are eagerly awaited.     

Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer

Purpose  Combination of intravenous (i.v.) vinorelbine and capecitabine was shown to be feasible and effective in metastatic breast cancer (MBC). In an effort to improve patient convenience and to prolong infusion-free survival, we investigated in first-line treatment a regimen combining oral vinorelbine and capecitabine in a phase II study. Patients and methods  Fifty-two patients (median age, 60 years) with MBC received the combination consisting of oral vinorelbine 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, multicentre phase II study [the recommended doses were established in a phase I study (Nolé et al. in Ann Oncol 17:332–339, 2006)]. Cycles were repeated every 3 weeks. Results  Seventy-nine percent of the patients had received prior adjuvant chemotherapy and 81% presented with visceral involvement. The median number of administered cycles per patient was 7 (range 1–18). Twenty-three responses were documented and validated by an independent panel review, yielding response rates of 44.2% (95% CI, 30.5–58.7) in the 52 enrolled patients and 54.8% (95% CI, 38.7–70.2) in the 42 evaluable patients. Median progression-free survival and median overall survival were 8.4 and 25.8 months, respectively. Neutropenia was the main dose-limiting toxicity but complications were uncommon, only one patient having experienced febrile neutropenia. Other frequently reported adverse events included, fatigue, nausea, vomiting, diarrhoea and constipation, stomatitis and hand-foot syndrome, which were rarely severe. Conclusions  This regimen combining oral vinorelbine with capecitabine is effective and manageable in the first-line treatment of MBC. Oral vinorelbine on days 1, 8 and 15 with capecitabine from days 1 to 14 every 3 weeks represents a convenient option which offers an all-oral treatment to the patients and prolongs their infusion-free survival.