卡培他滨在乳腺癌治疗中的临床应用

卡培他滨是一种新型口服氟尿嘧啶类药物,目前广泛用于乳腺癌、胃肠道肿瘤及头颈部肿瘤的治疗。无论是单药还是联合用药,卡培他滨在乳腺癌的治疗中均显示了其优越性。     

卡培他滨维持治疗晚期乳腺癌的临床观察

背景与目的：卡培他滨是晚期乳腺癌一线治疗方案用药,但在晚期乳腺癌的维持治疗中的研究较少。本文旨在探讨卡培他滨维持治疗晚期乳腺癌的疗效及不良反应。方法：将一线化疗后处于完全缓解(complete response,CR)、部分缓解(partial response,PR)或疾病稳定(stable disease,SD)的62例患者分为2组,卡培他滨治疗组(31例)患者予以单药口服卡培他滨维持治疗,对照组(31例)患者予以定期随访观察。每2个化疗周期后评价疗效。结果：卡培他滨治疗组中位疾病进展时间(time to progression,TTP)为12(2～24)个月,明显高于对照组的7(1～18)个月,且2组差异有统计学意义(P<0.05)。在亚组分析中,未绝经组、激素受体阳性组、HER-2阳性组、有内脏转移组、有肺转移组及既往未接受过卡培他滨化疗组的患者中,卡培他滨治疗组患者的TTP均显著高于对照组患者。卡培他滨治疗组总有效率(CR+PR)为19.4%(6/31),肿瘤控制率(CR+PR+SD)为74.2%(23/31)。主要不良反应为手足综合征及血液学不良反应,其次为胃肠道不良反应,但均可以耐受。卡培他滨治疗组的生活质量评分较对照组明显提高。结论：卡培他滨用于晚期乳腺癌一线治疗后的维持治疗可以延缓疾病进展,提高生活质量。     

含卡培他滨联合方案一线化疗后卡培他滨维持治疗转移性乳腺癌临床观察

目的:探讨转移性乳腺癌含卡培他滨联合方案一线化疗后继续卡培他滨维持化疗的疗效和毒副反应。方法:入组20例转移性乳腺癌患者,一线采用多西他赛/吉西他滨/长春瑞滨联合卡培他滨化疗6个周期,疗效评价无进展的患者采用卡培他滨维持化疗持续到疾病进展或出现不能耐受毒副反应为止。结果:一线治疗CR 1例,PR 7例,SD 12例,卡培他滨平均维持化疗周期为10个周期。中位PFS为12.2个月,中位TTP为7.7个月,中位OS为20.2个月。主要毒副反应为手足综合征、骨髓抑制、腹泻等,均可控制。结论:卡培他滨可作为转移性乳腺癌的维持治疗,可改善患者生存,毒副反应轻。     

卡培他滨联合调强放疗治疗乳腺癌肝转移的疗效观察

 目的 探讨卡培他滨联合调强放疗（intensity modulated raduation therapy, IMRT）并序贯卡培他滨治疗乳腺癌肝转移的疗效和不良反应。方法 将52例乳腺癌肝转移患者分为卡培他滨联合放疗组27例和卡培他滨治疗组25例。卡培他滨联合放疗组肝转移灶行IMRT,6 MV-X线照射,以95％剂量曲线包绕99%计划靶区,常规分割,2 Gy/次,1次/d,5次/周,共  4～6周,同时给予卡培他滨1 250 mg/m²,2次/d口服同步化疗,放疗结束后给予卡培他滨2 510 mg/m²,2次/d口服,21 d为1个周期。卡培他滨治疗组仅给予卡培他滨2 510 mg/m²,2次/d口服,21 d为1个周期。比较两组疗效及不良反应。结果 卡培他滨联合放疗组和卡培他滨治疗组有效率（RR）分别为74.1%和44%,肿瘤控制率分别为92.6%和68%,两组比较差异均有统计学意义（P>0.05）;中位缓解时间分别为13.6个月和8.9个月,中位生存时间分别为17.4个月和11.7个月,1年生存率分别为85.2%和56.0% (χ²=5.38,P,2年生存率分别为40.7%和16.0% (χ²=3.84,P＜0.05)。不良反应主要有中性粒细胞减少、胃肠道反应、肝功能损伤等,均以Ｉ级、Ⅱ级为主,卡培他滨联合放疗组Ｉ级、Ⅱ级不良反应发生率高于卡培他滨治疗组（P＜0.05）,但两组Ⅲ级、Ⅳ级不良反应发生率差异无统计学意义（P>0.05）。结论 卡培他滨联合调强放疗并序贯卡培他滨治疗乳腺癌肝转移远期生存率优于单药卡培他滨维持治疗,不良反应可耐受,是一种有效的治疗方案。     

选择性靶向化疗药物卡培他滨在乳腺癌治疗中的应用

卡培他滨是新一代口服氟尿嘧啶类药物,通过选择性靶向作用于高表达胸腺嘧啶磷酸化酶(TP)的肿瘤部位发挥抗肿瘤作用.体外实验发现许多化疗药物可以上调TP酶活性,从而提高抗肿瘤活性.现综述最新临床试验,探讨卡培他滨在乳腺癌治疗中的应用.     

选择性靶向化疗药物卡培他滨在乳腺癌治疗中的应用

卡培他滨是新一代口服氟尿嘧啶类药物，通过选择性靶向作用于高表达胸腺嘧啶磷酸化酶(TP)的肿瘤部位发挥抗肿瘤作用。体外实验发现许多化疗药物可以上调TP酶活性，从而提高抗肿瘤活性。现综述最新临床试验，探讨卡培他滨在乳腺癌治疗中的应用。     

卡培他滨单药或联合方案治疗晚期乳腺癌的疗效和安全性

目的 探讨卡培他滨单药或联合方案治疗晚期乳腺癌的疗效和安全性.方法 376例晚期乳腺癌患者接受如下方案治疗:(1)卡培他滨+多西紫杉醇方案:卡培他滨1000 mg/m2,口服,2次/d,第1～ 14天;多西紫杉醇60 ～75 mg/m2,静脉滴注,第1天;21 d为1个周期.(2)卡培他滨+长春瑞滨方案:卡培他滨1000 mg/m2,口服,2次/d,第1～14天;长春瑞滨25 mg/m2,静脉滴注,第1、8天;21 d为1个周期.中位治疗3个周期.(3)卡培他滨单药方案:卡培他滨1000 mg/m2,口服,2次/d,第1 ～ 14天,21 d为1个周期.结果卡培他滨单药组患者的有效率(ORR)为12.8％,临床获益率( CBR)为21.6％.一线治疗患者的ORR( 14.8％)与二线或二线以上治疗患者的ORR (12.2％)差异无统计学意义(P＞0.05),但一线治疗患者的CBR( 35.2％)高于二线或二线以上治疗者(17.1％),差异有统计学意义(P＜0.01).卡培他滨联合多西紫杉醇组患者的ORR为53.8％,其中一线治疗患者的ORR(48.5％)与二线或二线以上治疗患者的ORR(57.4％)比较,差异无统计学意义(P＞0.05).卡培他滨联合长春瑞滨组患者的ORR为36.4％,其中一线治疗患者的ORR (60.0％)明显高于二线或二线以上治疗患者(16.7％),差异有统计学意义(P＜0.01).结论 卡培他滨单药或者含卡培他滨联合方案不仅可以用于晚期乳腺癌一线治疗,也是二线或二线以上治疗的有效选择方案,患者不良反应可耐受.联合化疗有效后序贯至单药可以进一步延长乳腺癌患者的治疗时间.     

吉西他滨联合国产卡培他滨治疗晚期三阴性乳腺癌的临床观察

目的 观察吉西他滨联合国产卡培他滨化疗方案治疗晚期三阴性乳腺癌的近期疗效和安全性.方法 采用吉西他滨联合国产卡培他滨化疗方案治疗21例既往曾接受过蒽环类、紫杉类化疗失败的晚期三阴性乳腺癌者,2周期化疗后评价近期疗效和不良反应.结果 21例患者中,CR 1例,PR 6例,SD 9例,PD 5例,有效率为33.3%.不良反应主要为Ⅰ、Ⅱ度血液学毒性、消化道反应和手足综合征等.结论 吉西他滨联合国产卡培他滨化疗方案治疗晚期三阴性乳腺癌安全有效,值得临床推广应用.     

卡培他滨维持治疗转移性乳腺癌的疗效观察

目的:观察卡培他滨维持治疗转移性乳腺癌的疗效和毒副反应。方法:2009年10月-2013年7月,31例转移性乳腺癌一线或二线含卡培他滨联合化疗4-6个周期后,疾病达缓解或稳定的患者,接受卡培他滨维持治疗,卡培他滨1000mg/m2,d1-14,休息7天,21天为1个周期,维持化疗进展或不能耐受毒副反应者化疗停止,每个患者接受至少2个周期维持治疗。结果:卡培他滨维持治疗转移性乳腺癌有效率（RR）为6.5%,临床获益率（CBR）（＞6个月）为35.5%,疾病控制率（DCR）为74.2%,中位无进展生存期（PFS）为5.8个月。主要的毒副反应为手足综合征（HFS）,发生率为67.7%,多为Ⅰ-Ⅱ度,1例Ⅲ度患者应用大剂量维生素B6且卡培他滨减量后好转。Ⅲ-Ⅳ度白细胞、中性粒细胞下降分别为9.7%和12.9%,明显低于卡培他滨联合化疗时Ⅲ-Ⅳ度白细胞、中性粒细胞下降发生率的35.5%和38.7%（P＜0.05）。结论:卡培他滨是维持治疗转移性乳腺癌的有效药物,患者耐受性好,毒副反应较轻。     

卡培他滨联合顺铂治疗复治的晚期食管癌胃癌

恶性消化道肿瘤一般发现比较晚,术后大部分患者要复发或远处转移,治疗效果一般较差。新药卡培他滨 [1]已经在乳腺癌、结直肠癌的治疗中显示出了良好的疗效。自 2002年 1月至 2003年 10月我们将卡培他滨联合顺铂用于复治的晚期食管癌和胃癌患者,获得了良好的临床结果。1　材     

Role of capecitabine (Xeloda) in breast cancer

One rationale for the development of new treatment strategies for advanced breast cancer is to provide targeted antineoplastic therapy, while at the same time improving the quality of life of patients. One such drug, capecitabine (Xeloda), is an oral fluoropyrimidine 5-fluorouracil carbamate. Capecitabine is converted to 5-fluorouracil primarily in cancer tissue and it has been demonstrated to combine ease of administration, a manageable toxicity profile and potent antineoplastic activity. Capecitabine is widely used in metastatic breast cancer and offers symptom palliation and in combination with docetaxel (Taxotere) improved survival compared with docetaxel alone. Its toxicity profile includes hand-foot syndrome and stomatitis and diarrhea, whereas its hematologic side effects are mild. Capecitabine has been evaluated as a single agent in women with advanced breast cancer where it offers an overall response rate of 20-30%. Capecitabine is synergistic with other chemotherapeutic agents, such as the taxanes, where it increases the response rate to over 40%. This review will place the available data on the use of capecitabine in metastatic breast cancer as a single agent or as part of a combination regime in context.     

Capecitabine--a review of its antitumor activity and toxicity in clinical studies

Capecitabine is a novel fluoropyrimidine carbamate, orally administered and rationally designed to undergo tumor-selective activation. Some studies have been proven it to be safe for outpatient treatment and to have significant antitumor activity in colorectal and breast cancer patients. Randomized trials of patients with advanced colorectal cancer using capecitabine versus Leucovorin (LV).5-FU were studied in two groups. Capecitabine results in both a higher response rate and a more favorable toxicity profile than LV.5-FU. In women aged 55 years or more with breast cancer, capecitabine showed at least comparable efficacy to CMF combination therapy. Capecitabine offers a new effective oral treatment option as a single agent for patients with advanced colorectal or breast cancer.     

Role of capecitabine (Xeloda®) in breast cancer

One rationale for the development of new treatment strategies for advanced breast cancer is to provide targeted antineoplastic therapy, while at the same time improving the quality of life of patients. One such drug, capecitabine (Xeloda^®), is an oral fluoropyrimidine 5-fluorouracil carbamate. Capecitabine is converted to 5-fluorouracil primarily in cancer tissue and it has been demonstrated to combine ease of administration, a manageable toxicity profile and potent antineoplastic activity. Capecitabine is widely used in metastatic breast cancer and offers symptom palliation and in combination with docetaxel (Taxotere^®) improved survival compared with docetaxel alone. Its toxicity profile includes hand–foot syndrome and stomatitis and diarrhea, whereas its hematologic side effects are mild. Capecitabine has been evaluated as a single agent in women with advanced breast cancer where it offers an overall response rate of 20–30%. Capecitabine is synergistic with other chemotherapeutic agents, such as the taxanes, where it increases the response rate to over 40%. This review will place the available data on the use of capecitabine in metastatic breast cancer as a single agent or as part of a combination regime in context.     

Mechanism and possible biochemical modulation of capecitabine (Xeloda), a newly generated oral fluoropyrimidine

A new 5-FU analog, Capecitabine (Xeloda; N-[1-(5-deoxy-b-D-ribofuranosyl)-5-fluoro-1, 2-dihydro-2-oxo-4-pyrimidyl]-n-penyl carbamate), was generated to decrease the incidence of GI toxicity and to increase the efficacy. Capecitabine is designed as a prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR), which is clinically used for gastric, breast and colorectal cancer patients undergoing single or combination chemotherapy in Japan. Capecitabine was converted to 5'-DFUR by either human carboxyestelase or cytidine deaminase, which were mainly localized in human liver. 5'-DFUR was converted to the active form of 5-FU by thymidine phosphorylase (dThdPase) in human tumors. The expression of dThdPase was higher in malignant tumors than in noninvolved normal tissues. In this regard, a high concentration of either 5'-DFUR or 5-FU in malignant tumors may be obtained by oral administration of Capecitabine. In addition, in vivo study showed synergistic or additive effects of Capecitabine combined with anti-cancer agents (Taxanes, Mitomycin C or Cyclophosphamide), cytokines, growth factors and hormonal agents. Capecitabine may be biochemically modulated by those agents in vivo. In the results of an early phase II study on breast cancer patients in Japan, a high efficacy rate and low toxicity were observed. Also, Capecitabine was already registered as 2nd- or 3rd-line treatments for breast cancer patients by the Food & Drug Administration of the USA. Capecitabine is one of the most promising orally administered 5-FU analogs.     

Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells

Background  

Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.     

Capecitabine: indications and future perspectives in the treatment of metastatic colorectal and breast cancer

Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.     

The evolving role of capecitabine in breast cancer

Breast cancer is the most common cancer and the second greatest cause of cancer-related death among women in the United States. Capecitabine is a selectively tumor-activated fluoropyrimidine carbamate that is converted to 5-fluorouracil by the sequential activity of these enzymes, the final of which is thymidine phosphorylase, which is overexpressed in many human cancers. Capecitabine as a single agent and in combination with other drugs is efficacious in previously treated and untreated metastatic breast cancer (MBC). The integration of capecitabine, either as a single agent or in combination with docetaxel, into adjuvant breast cancer therapy is justified due to its high antitumor activity in previously treated and untreated MBC, its tolerability, lack of cross-resistance with the anthracyclines and taxanes, and because combined docetaxel/capecitabine improves the overall survival of patients with MBC. Capecitabine is being evaluated as preoperative therapy in patients with operable breast cancer, as adjuvant therapy in patients with high-risk node-negative or node-positive disease, and as oral single-agent therapy in women > or = 65 years of age. This article is an overview of published studies of capecitabine in MBC and the studies that are planned or have been proposed to evaluate capecitabine as adjuvant therapy for breast cancer.     

Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

Several chemotherapic agents, which are active againstbreast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.     

参一胶囊联合卡培他滨治疗晚期乳腺癌临床观察

目的评价参一胶囊联合卡培他滨治疗晚期乳腺癌的疗效、机制及对化疗不良反应和生活质量的影响。方法采用前瞻性随机对照研究,把56 例晚期乳腺癌患者分为治疗组与对照组。治疗组28例,给予参一胶囊联合卡培他滨治疗;对照组28例单纯给予卡培他滨治疗。结果治疗组和对照组有效率分别为35.7%、25%。1年生存率分别为68%、50%,差异均无统计学意义。治疗组白细胞减少率和疲劳发生率分别为17.9%、7.1%,对照组分别为42.9%、32.1%,两组白细胞减少率、疲劳发生率比较差异均有统计学意义。治疗组与对照组相比能显著降低VEGF的值,提高了生活质量。结论参一胶囊联合卡培他滨治疗晚期乳腺癌有提高患者生存期的趋势,并可以减少化疗引起的疲劳、白细胞降低等不良反应,提高患者的生活质量等,其机制可能与参一胶囊有抗血管生成作用等有关。     

吉西他滨联合卡培他滨治疗蒽环类和紫杉类耐药的转移性乳腺癌

目的:观察吉西他滨(Gemcitabine)联合卡培他滨(Capecitabine)治疗蒽环类和紫杉类药物耐药的转移性乳腺癌患者的近期疗效和不良反应。方法:40例患者采用吉西他滨联合卡培他滨方案化疗:吉西他滨1000mg/m2静脉滴注,第1、8天;卡培他滨1000mg/m2口服,每日两次,第1-14天;21天为1周期。每2周期评价疗效,每周期进行毒性和安全性评估。结果:40例患者共接受156周期化疗,中位化疗周期4个(2-6个周期),总有效率(overall remission rate,RR)为35.00%(14/40),其中临床完全缓解率(clinical completeremission,cCR)为7.50%(3/40),部分缓解率(partial remission,PR)为27.50%(11/40),稳定率(stable dis-ease,SD)为30.00%(12/40),进展率(progressive disease,PD)为35.00%(14/40)。结论:吉西他滨联合卡培他滨是治疗蒽环类和紫杉类药物耐药的转移性乳腺癌的有效方案,其血液学和非血液学毒性耐受性良好。