长春瑞滨联合卡培他滨治疗蒽环类及紫杉类耐药的转移性三阴乳腺癌的临床观察

目的观察长春瑞滨联合卡培他滨治疗蒽环类及紫杉类耐药的转移性三阴性乳腺癌患者的疗效和不良反应。方法 32例蒽环类及紫杉类耐药的复发转移性三阴性乳腺癌患者接受长春瑞滨联合卡培他滨化疗,长春瑞滨25mg/m2,静脉滴注,第1天和第8天,采用深静脉穿刺置管技术静脉滴注;卡培他滨825～1000mg/m2,口服,每天2次,第1～14天;21d重复。统计分析其疗效与不良反应。结果 32例患者共接受152个周期治疗,中位治疗周期数为4个周期(2～6个周期);11例患者获得部分缓解(PR,占34.4%),9例患者获得稳定(SD,占28.1%),其中5例患者稳定维持6个月以上;12例患者获进展(PD,占37.5%)。总有效率(CR+PR)34.4%(11/32),疾病控制率(PR+SD)62.5%(20/32),中位疾病进展时间(TTP)为5.4个月。常见不良反应为骨髓抑制,恶心、呕吐和手足综合征等。结论长春瑞滨联合卡培他滨方案近期疗效好,毒性可以耐受,可作为蒽环类及紫杉类耐药的转移性三阴性乳腺癌患者治疗的选择。     

卡铂联合长春瑞滨治疗晚期乳腺癌的临床研究

目的 对比分析卡铂联合长春瑞滨和长春瑞滨单药治疗晚期乳腺癌的疗效。方法 60例复发转移乳腺癌患者,随机分成联合组和单药组,每组30例。联合组采用卡铂联合长春瑞滨化疗方案,单药组采用长春瑞滨化疗方案。对比分析两组有效率。结果 单药组患者有效率(CR+PR)为33%,联合组患者有效率为40%,两组比较差异有统计学意义(P<0.05)。结论 卡铂联合长春瑞滨较单用长春瑞滨治疗复发转移性乳腺癌疗效好,主要不良反应为骨髓抑制。两者联合可作为蒽环类及紫杉类耐药的复发转移性乳腺癌的选择。     

卡培他滨联合多西紫杉醇治疗晚期蒽环类耐药乳腺癌临床观察

乳腺癌是严重危害女性健康和生命的恶性肿瘤,占恶性肿瘤20％,死亡率为15／150000～25／150000左右,且发病率以每年1％增长。乳腺癌也是女性癌症致死最主要的原因。晚期乳腺癌以姑息化疗及内分泌治疗为主,随着蒽环类药物在乳腺癌治疗中的广泛应用,对蒽环类耐药患者日渐增多,如何治疗蒽环类耐药的转移复发性乳腺癌已成为临床肿瘤医生难题。目前可用于复发、转移性乳腺癌二线治疗的药物有卡培他滨、紫杉类、长春瑞滨、吉西他滨等。我们2005年1月至2008年1月对葸环类药物治疗失败的晚期乳腺癌患者24例,采用卡培他滨联合多西他赛治疗,取得较好的疗效,报告如下。     

吉西他滨及长春瑞滨联合顺铂对晚期耐药乳腺癌的治疗观察

目的：观察吉西他滨及长春瑞滨分别联合顺铂的化疗方案治疗对蒽环类和紫杉类耐药的复发转移性晚期乳腺癌的疗效及不良反应。方法：将56例乳腺癌患者随机分为A、B两组各28例,A组应用吉西他滨1000mg/m2进行静脉滴注30min,第1、8天;顺铂25mg/m2静脉滴注,第1～3天。B组应用长春瑞滨25mg/m2静脉滴注,第1、8天;顺铂用法同A组。每21天为1个周期,至少化疗2个周期后评价疗效。结果：A组总有效率为57.1%,B组总有效率为53.6%,两组疗效差异无统计学意义。结论：吉西他滨及长春瑞滨联合顺铂方案治疗对蒽环类和紫杉类耐药的晚期乳腺癌疗效较好,不良反应可以耐受。     

洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的临床观察

目的探讨洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的疗效及不良反应。方法36例蒽环类和紫杉类化疗失败的晚期乳腺癌患者,给予洛铂联合卡培他滨化疗：洛铂30mg／m^2,d1;卡培他滨每日2500mg／m。,分2次口服,d1～d14,3周为1周期。2周期后按wHO标准评价疗效及不良反应。结果36例患者均可评价疗效及不良反应,其中获CR2例,PR11例,SD12例,PD11例,有效率为36．1％,疾病控制率为69．49／6。主要不良反应为骨髓抑制和消化道反应,以1、2级为主,经对症处理后均可耐受。结论洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的疗效较好,不良反应可耐受。     

长春瑞滨联合卡培他滨治疗转移性乳腺癌的临床研究

目的观察长春瑞滨联合卡培他滨对紫杉类和/或蒽环类药物治疗后失败的转移性乳腺癌的疗效、安全性。方法39例晚期乳腺癌患者均给予长春瑞滨25mg·m^-2,第一,八天;希罗达口服,950mg·m^-2,1日2次,餐后服用,连续服用14d。21d为1周期,至少完成2周期化疗。每周期评价毒性反应,2周期化疗后评价疗效。结果39例患者有效率达46.2%。无CR病人,PR18例（46.2%）,SD13例（33.3%）,PD8例（20.5%）。中位肿瘤进展时间（TTP）为6.4个月（1～18个月）。最常见的不良反应为手足综合征、骨髓抑制、神经毒性、胃肠道反应等,多为轻度到中度。结论长春瑞滨联合卡培他滨对紫杉类和/或蒽环类药物治疗后失败的转移性乳腺癌有较好的疗效,毒性可以耐受。     

FDA批准依扎匹隆注射剂上市

FDA批准百时美施贵宝公司的埃博霉素B半合成同系物依扎匹隆注射剂（ixabepilone，Ixempra）上市，治疗对蒽环类、紫杉醇类和卡培他滨等药物耐药的转移性或晚期局限性乳腺癌患者。FDA还批准依扎匹隆与卡培他滨联用治疗对蒽环类、紫杉醇类药物或肿瘤抗紫杉醇类药物耐药而再用蒽环类药物治疗有禁忌的转移性或晚期局限性乳腺癌患者。     

卡培他滨联合顺铂治疗晚期乳腺癌的临床研究

目的 探讨卡培他滨联合顺铂治疗蒽环类及紫杉类耐药的晚期乳腺癌的临床效果.方法 选取解放军第三二三医院肿瘤中心的19例蒽环类及紫杉类耐药的晚期乳腺癌患者,给予卡培他滨联合顺铂治疗,21 d为1个周期,所有患者均治疗2个周期以上,观察临床疗效及不良反应.结果 19例患者中完全缓解1例,部分缓解9例,稳定6例,进展3例,总有效率为52.6％.中位无疾病进展生存期6.0个月（95％CI：4.4 ～7.6个月）,中位生存期15.0个月（95％ CI：13.0 ～ 16.9个月）.主要的毒性反应有骨髓抑制、乏力、胃肠道反应及手足综合征等,为可逆性,无治疗相关死亡.结论 卡培他滨联合顺铂疗效较好,毒性反应可耐受,可作为蒽环类及紫杉类耐药的晚期乳腺癌患者的治疗选择.     

长春瑞滨联合希罗达冶疗晚期及复发转移乳腺癌临床疗效观察

目的探讨晚期及复发转移乳腺癌患者采取长春瑞滨(盖诺)联合希罗达(卡培他滨)治疗的临床效果。方法回顾性分析28例经蒽环类和紫杉类化疗后复发的晚期及复发转移乳腺癌患者的临床资料,皆予以长春瑞滨联合希罗达治疗,对比分析其临床效果及不良反应情况。结果 28例患者经治疗后,临床总有效率为78.57%(22/28);不良反应主要有12例手足综合征、17例白细胞下降、15例恶心呕吐、8例血小板下降、10例血红蛋白下降、15例脱发等。结论晚期及复发转移乳腺癌患者采取长春瑞滨联合希罗达治疗可以取得比较良好的效果,疗效确切,虽然不良反应较多,但皆可耐受,值得借鉴。     

长春瑞滨联合吉西他滨治疗晚期乳腺癌50例临床分析

目的 观察长春瑞滨（NVB）联合吉西他滨（GEM）治疗蒽环类和紫杉类药物耐药的晚期乳腺癌患者（ATRMBC）的临床效果. 方法 采用NVB联合GEM方案（GN方案）治疗50例蒽环类和紫杉类药物耐药的晚期乳腺癌患者,NVB 25 mg/m2静脉滴注,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 50例患者完全缓解2例（4%）,部分缓解19例（38%）,稳定22例（44%）,进展7例（14%）;有效率42%;平均随访17.2个月,中位生存期16.8个月.主要不良反应为恶心、呕吐及骨髓抑制. 结论 NVB联合GEM是治疗蒽环类和紫杉类药物耐药的晚期乳腺癌患者的有效方案,患者对不良反应能够耐受.     

Single-agent capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer

We performed an analysis of the efficacy of capecitabine monotherapy as maintenance treatment for metastatic breast cancer (MBC) after response to capecitabine-based chemotherapy [capecitabine plus docetaxel (XT) or vinorelbine (XN)] as a first-line or a second-line treatment. Sixty-four Chinese patients with histologically confirmed MBC received capecitabine maintenance therapy after disease stabilization or maximal response to capecitabine-based combination chemotherapy. Single-agent capecitabine was administered at a dose of 1000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, every 3 weeks. The median time to progression, the primary endpoint of the study, was 4.4 months (95% confidence interval, 3.4-5.4 months). Fifty-nine patients were evaluable for response. Capecitabine maintenance therapy produced an objective response rate of 5.1% (95% confidence interval, 3.9-6.3%). The incidence of grade 3/4 leukopenia (3.1%) and neutropenia (4.7%) was significantly lower (P<0.001) with capecitabine monotherapy than with combination chemotherapy (46.9 and 54.7%, respectively). Conversely, the incidence of grade 3 hand-foot syndrome was higher with capecitabine maintenance therapy than with combination therapy (14.1 vs. 0%, respectively; P=0.003). Capecitabine monotherapy is an effective maintenance treatment after response to capecitabine-based combination chemotherapy in MBC with a favorable safety profile.     

Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy

Clinical characteristics and risk factors of hand-foot syndrome were investigated in patients who received capecitabine-containing chemotherapy. Toxicity data were analyzed from 179 patients in 4 prospective clinical trials testing docetaxel/capecitabine/cisplatin in stomach cancer, capecitabine/cisplatin in biliary or stomach cancer, and vinorelbine/capecitabine in breast cancer. Hand-foot syndrome was reported in 116/179 (64.8%) of patients, with grade 3 hand-foot syndrome in 8/179 (4.5%). Hand-foot syndrome first developed within the first 3 chemotherapy cycles in 100/116 (86.2%) patients, with the median onset for all 3 treatment regimens occurring during cycle 2. Because severe reactions were rare, hand-foot syndrome was not a major factor influencing treatment schedule. Risk factor analyses showed that combined use of docetaxel and preceding chemotherapy-related stomatitis were significant risk factors for the development of hand-foot syndrome. Our results suggest that a combined treatment agent and a patient's susceptibility to chemotherapy-related toxicity may increase the risk of capecitabine-induced hand-foot syndrome.     

Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). We herewith report on a patient suffering from HER2 overexpressing MBC who received intrathecal methotrexate and trastuzumab for meningeal carcinomatosis. A 48-year-old woman was diagnosed with breast cancer in December 2002. Following surgery, six cycles of adjuvant FE100C plus irradiation and, subsequently for 1 year, trastuzumab were given. As a result of disseminated metastatic spread in October 2005, the patient received whole-brain radiotherapy for symptomatic central nervous system involvement, and was put on several trastuzumab-based combination regimens (capecitabine, vinorelbine, paclitaxel). In June 2006, the patient developed clinical signs of terminal cone involvement with overflow incontinence and paraparesis of the legs. Immediate radiation led to partial relief from clinical symptoms. Subsequently, the patient was put on the tyrosine kinase inhibitor lapatinib and capecitabine (August to October 2007), but on November 6th the patient suffered again from overflow incontinence and weakness of the legs. Failing to respond to lapatinib, the patient received gemcitabine/cisplatin and, additionally, was recommenced on intravenous trastuzumab. Owing to progressive leptomeningeal disease, the patient received repeated doses of intrathecal methotrexate and trastuzumab. Within 2 weeks and four intrathecal treatments, cerebrospinal fluid cytology showed the absence of tumor cells. Moreover, a striking clinical improvement with resolution of the paraparesis of the legs and overflow incontinence was observed. This case report gives details regarding the clinical course of a breast cancer patient who received intrathecal trastuzumab and methotrexate via lumbar puncture for meningeal carcinomatosis of HER2-overexpressing MBC.     

吉西他滨联合卡培他滨治疗晚期乳腺癌的疗效观察

目的：观察吉西他滨联合卡培他滨治疗晚期乳腺癌的临床疗效和不良反应。方法：吉西他滨1000mg/m2,1、8d;卡培他滨2500mg/（m2·d）,分2次口服,第1～14天,21d为1个周期。所有患者均接受至少2个周期的化疗。结果：48例患者入组均可评价疗效,CR率为12.5%（6/48）,PR率为29.2%（14/48）,SD率为20.8%（10/48）,PD率为37.5%（18/48）。有效率为41.7%（20/48）,临床获益率为62.5%（30/48）。中位随访期10个月,中位TTP7个月,中位OS9.5个月,1年生存率为66.7%。主要不良反应为骨髓毒性及手足综合征,Ⅲ度及Ⅳ度白细胞减少为22.9%（11/48）,Ⅲ度及Ⅳ度血小板减少为18.8%（9/48）。手足综合征发生率为70.8%,其中,Ⅲ度及Ⅳ度手足综合征发生率为16.7%（8/48）。结论：吉西他滨联合卡培他滨方案治疗蒽环类和紫杉类化疗失败的转移性乳腺癌有较好的疗效,患者耐受性好,值得临床进一步研究。     

卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌临床研究

目的探讨卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌临床疗效与安全性。方法20例转移性乳腺癌病例,卡培他滨采用500 mg tid,连续口服第1-14天;国产多西紫杉醇25 mg.m^-2,静脉滴注持续1 h,第1、8 d给药。每21 d重复。结果20例中CR1例,PR11例,SD4例,PD4例,RR为60%（12/20）,DCR为80%（16/20）。不良反应为Ⅰ-Ⅱ度白细胞下降、关节肌肉酸痛及手足综合征,Ⅰ度消化道反应,Ⅲ度不良反应少见,无Ⅳ度不良反应。结论应用卡培他滨联合多西紫杉醇节拍化疗治疗转移性乳腺癌,具有疗效好、副作用小及患者依从性好等优点。     

Biweekly docetaxel and vinorelbine with granulocyte colony-stimulating factor support for patients with anthracycline-resistant metastatic breast cancer

This phase II trial evaluated the efficacy and toxicity of vinorelbine 25 mg/m2 plus docetaxel 60 mg2/m administered on day 1, every 2 weeks with granulocyte colony-stimulating factor support (G-CSF, 5 microg/kg/day, days 3-7) as primary prophylaxis in patients with histologically confirmed metastatic breast cancer (MBC) and previously treated with anthracyclines in the adjuvant or in the first-line setting. A total of 48 patients received 352 cycles (median 8, range 2-10). All patients were included in the efficacy and safety evaluation on an intent-to-treat analysis. Eight patients (17%) showed a complete response and 14 patients (29%) showed a partial response. Overall response rate was 46% [95% confidence interval (CI) 33-60]. The median duration of response was 10.0 months. With a median follow-up of 18.0 months, the median time to progression was 11.9 months and the median overall survival was 27.1 months. The most frequently reported grade 3/4 hematological toxicity was neutropenia (19% of patients, 4% of cycles). Febrile neutropenia was reported in six patients (13%) and 7 cycles (2%), but no toxic deaths were reported. The most common grade 3/4 non-hematological toxicity was asthenia (17% of patients, 6% of cycles) and nail toxicity (15% of patients, 3% of cycles). In conclusion, biweekly docetaxel plus vinorelbine with G-CSF support is active and well tolerated as chemotherapy for patients with MBC resistant to anthracyclines. G-CSF support is recommended for lowering the incidence and severity of neutropenia and febrile neutropenia.     

Capecitabine: new indication. In breast cancer: inadequately assessed

There is no consensus on treatment of locally advanced or metastatic breast cancer after failure of first-line cytotoxic chemotherapy. Common options are continuous infusion of a taxane (docetaxel or paclitaxel), vinorelbine or fluorouracil. Capecitabine is now licensed for use in breast cancer, both in combination with IV docetaxel after anthracycline failure, and as single-agent therapy after failure of anthracyclines and taxanes. The clinical evaluation dossier on capecitabine fails to answer the most important questions about comparative efficacy and safety. In second-line treatment, after anthracycline failure, the only available comparative trial showed that the capecitabine + docetaxel combination increased median survival time by about three months relative to placebo + docetaxel, but caused more adverse events. There are no trials comparing capecitabine with other options. There is no evidence that capecitabine increases the length or quality of survival, relative to intravenous vinorelbine, in women with breast cancer that is resistant to both anthracyclines and taxanes. The classical adverse effects of capecitabine are also observed in women with breast cancer, namely palmoplantar erythrodysesthesia, diarrhoea, nausea and vomiting, and major hyperbilirubinemia. Capecitabine can be taken by mouth and this may be an advantage. However, current evidence is too limited to justify using capecitabine outside of clinical trials.