Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated,advanced breast carcinoma

BACKGROUND: The objective of this study was to evaluate the activity and safety of oral capecitabine in combination with docetaxel and epirubicin (TEX) as first-line treatment for patients with locally advanced/metastatic breast carcinoma. METHODS: This open-label, Phase II study was conducted at six Italian centers. Treatment consisted of epirubicin, 75 mg/m(2) (intravenous bolus), and docetaxel, 75 mg/m(2) (1-hour infusion), both administered on Day 1, plus oral capecitabine, 1000 mg/m(2) twice daily, on Days 1-14 of each 3-week treatment cycle. RESULTS: A total of 67 patients received 392 cycles of treatment, with a median of 6 cycles in patients with Stage III disease (n = 34 patients) and a median of 8 cycles in patients with Stage IV disease (n = 33 patients). The objective response rate was 82%, including complete responses in 21% of patients. A greater proportion of patients with Stage III disease achieved tumor responses compared with patients who had Stage IV disease (97% vs. 67%, respectively). Among 34 patients with Stage III disease, pathologic complete responses were confirmed in 10 patients (29%). TEX chemotherapy demonstrated an acceptable safety profile. There was a low incidence of Grade 3 adverse events, and Grade 4 adverse events were particularly rare (4%). The most common Grade 3-4 adverse event was febrile neutropenia, which occurred in 16% of patients. CONCLUSIONS: TEX combination therapy has important antitumor activity and an acceptable safety profile in this setting. A large, randomized, Phase III trial is ongoing to compare TEX chemotherapy with an epirubicin plus docetaxel regimen in patients with untreated, advanced breast carcinoma.     

多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的临床观察

目的：观察多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的疗效与不良反应。方法：采用多西紫杉醇联合表阿霉素及环磷酰胺治疗56例复发或转移的晚期乳腺癌患者,多西紫杉醇75mg/m2,d1,表阿霉素50mg/m2,d1,环磷酰胺500mg/m2,d1,21天为1周期,连续治疗2周期。结果：56例患者TEC方案治疗2周期后CR7例,PR22例,总有效率为51.8%。最常见不良反应为骨髓抑制、消化道反应及脱发,本组无一例发生过敏反应,其不良反应可耐受。结论：TEC方案治疗晚期乳腺癌可作为晚期乳腺癌的一线治疗方案。     

A phase II study of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine and pegfilgrastim support as preoperative therapy for patients with stage II, IIIA breast cancer.

BACKGROUND: This phase II study was conducted to evaluate tumor response rate and safety profile of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine given preoperatively to patients with stage II or IIIA breast cancer. PATIENTS AND METHODS: Patients underwent four cycles of dose-dense cyclophosphamide 600 mg/m(2) and epirubicin 90 mg/m(2) every 2 weeks followed by two cycles of docetaxel 36 mg/m(2) on days 1, 8, and 15 plus capecitabine 1250 mg/m(2) on days 5-18 every 4 weeks, with prophylactic pegfilgrastim. The primary objective of the study was to determine the incidence of pathologic complete response defined as the absence of invasive or in situ cancer in the breast and the axillary nodes at definitive surgery. RESULTS: Forty-four patients were enrolled in the study and 41 (93%) were assessable for response to chemotherapy. An objective clinical response was observed in 38 (93%) patients. Seven patients (17.1%) exhibited a pathologic complete response. Breast-conserving surgery was carried out in 36 (88%) patients. Grade 3/4 neutropenia occurred in 4.3% of 252 administered chemotherapy cycles. No febrile neutropenia, cardiac toxicity, thrombocytopenia or other serious adverse event was registered. CONCLUSION: The sequential combination of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine is an effective and well-tolerated neo-adjuvant chemotherapy for stage II, IIIA breast cancer.     

DC方案与DE方案一线治疗转移性乳腺癌的对比研究

目的　比较多西紫杉醇联合卡培他滨（ＤＣ方案）与多西紫杉醇联合表柔比星（ＤＥ方案）一线治疗转移性乳腺癌的疗效及不良反应。方法　６５例转移性乳腺癌患者分别接受ＤＣ方案和ＤＥ方案治疗。ＤＣ方案组：多西紫杉醇７５ｍｇ／ｍ２静滴,ｄ１;卡培他滨２０００ｍｇ／（ｍ２·ｄ）,分两次口服,ｄ１～ｄ１４。ＤＥ方案组：多西紫杉醇７５ｍｇ／ｍ２静滴,ｄ１;表柔比星７５ｍｇ／ｍ２静推,ｄ１。两方案均以２１天为１个周期。结果　ＤＣ方案组有效率高于ＤＥ方案组（６０.６％ ｖｓ．４６.９％,Ｐ＞０.０５）,其中ＤＣ方案组完全缓解率高于ＤＥ方案组（２４.２％ ｖｓ．６.３％）,两组比较差异有统计学意义（Ｐ＜０.０５）。ＤＣ方案组的６个月后疾病无进展率（ＰＦＲ）优于ＤＥ方案组（７２.７％ ｖｓ．６２.５％,Ｐ＞０.０５）。中位无进展生存期（ＰＦＳ）ＤＣ方案组长于ＤＥ方案组（１１.４个月ｖｓ．７.６个月）,两组比较差异有统计学意义（Ｐ＜０.０５）。不良反应以骨髓抑制、胃肠道反应和脱发为主,３、４级手足综合征发生率ＤＣ方案组（２７.３％,９／３３）高于ＤＥ方案组（０）,差异有统计学意义（Ｐ＜０.０５）。结论　ＤＣ方案及ＤＥ方案一线治疗转移性乳腺癌均取得较好疗效,ＤＣ方案可以作为非蒽环类药物有效的一线治疗方案。     

多西他赛联合表阿霉素与多西他赛联合顺铂一线治疗晚期乳腺癌的临床研究

目的 评价多丙他赛联合表阿霉素(TE方案)与多西他赛联合顺铂(TP方案)一线治疗局部晚期或转移性乳腺癌患者的疗效和安全性.方法 88例患者按2:1随机进入TE组和TP组.TE组患者药物剂量为多西他赛75 mg/m2,表阿霉素60 mg/m2;TP组患者药物剂量为多西他赛75mg/m2,顺铂75 mg/m2. 21 d为1个周期,2个周期末评价近期疗效及安全性.结果 TE组可评价近期疗效者55例,其中CR 3例,PR 26例,SD 22例,PD 4例.TP组可评价近期疗效者27例,其中CR 1例,PR 16例,SD 9例,PD 1例.TE组和TP组近期有效率分别为48.3%和60.7%(P=0.2788),临床受益率分别为85.0%和92.9%(P=0.4899),中位肿瘤进展时间(TTP)分别为10个月和8个月(P=0.7119).Ⅲ、Ⅳ度不良反应主要为中性粒细胞减少,TE组和TP组发生率分别为66.7%和53.6%(P=0.2373);其次为脱发,TE和TP组分别为30.0%和10.7%(P=0.0508).结论 TE方案与TP方案一线治疗局部晚期或转移性乳腺癌的疗效和安全性相当.     

Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.     

多西紫杉醇联合卡培他滨治疗乳腺癌肝转移的临床研究

 目的 观察多西紫杉醇联合卡培他滨作为一线方案治疗乳腺癌肝转移的疗效及安全性。方法 42例乳腺癌肝转移患者采用多西紫杉醇75 mg／m2，静脉滴注，第1天，卡培他滨950 mg／m2， 2次／d，口服，第1天至第14天；每21天为1个周期，治疗至少2个周期评价疗效。结果 完全缓解（CR）4例，部分缓解（PR）19例，稳定（SD）9例，进展（PD）6例，总有效率为54.76 %（23／42），临床获益（CBR）率64.28 %，中位疾病进展时间（TTP）10.1个月，中位生存时间17.5个月。常见不良反应为白细胞和中性粒细胞减少（76.1 %和71.4 %）、手足综合征（45.2 %）和恶心、呕吐（52.3 %），多数为Ⅰ～Ⅱ度。结论 多西紫杉醇联合卡培他滨作为一线方案治疗乳腺癌肝转移疗效较高，安全性较好，不良反应可以耐受     

Epirubicin--docetaxel combination in first-line chemotherapy for patients with metastatic breast cancer: final results of a dose-finding and efficacy study

The aim of the study was to define a regular and tolerable dose of the epirubicin-docetaxel combination in first-line chemotherapy of patients with metastatic breast cancer. Sixty-five women with measurable and/or evaluable disease were treated with epirubicin escalated from 60 to 110 mg/m(2) according to 5 dose levels, in combination with a fixed dose of 75 mg/m(2) docetaxel, every 21 days for 6 cycles, without preventive use of hematopoietic growth factors or antibiotics. Forty-three women received adjuvant chemotherapy, consisting of anthracyline- or anthracenedione-based regimens in 39 cases (60%). Twenty-seven women were treated in the phase I study (3 at epirubicin 60 mg/m(2), and 6 at each subsequent dose level). Dose-limiting toxicity consisted of grade III asthenia and febrile neutropenia (epirubicin 75 mg/m(2)), grade IV thrombopenia and grade III asthenia (epirubicin 90 mg/m(2)), grade IV stomatitis and grade III diarrhea (epirubicin 100 mg/m(2)), and grade III diarrhea (epirubicin 110 mg/m(2)). In the phase II study, an additional 38 women were treated at epirubicin 90 mg/m(2) and epirubicin 100 mg/m(2). During the 349 cycles delivered, grade IV neutropenia occurred in 90%; febrile neutropenia requiring hospitalization occurred in 62 (17.8%) and lasted more than 3 days in 12 (3.4%). Nonhematologic toxicity was acceptable. Three left ventricular ejection fraction depressions occurred and normalized during follow-up. The overall response rate in the 62 evaluable women was 69.4% (range: 58--81%), with a median duration of 7.8 months. After 26 months of follow-up, the median time to progression was 9.1 months and median overall survival was 22.7 months. On the basis of efficacy and toxicity, the recommended dose of the combination is epirubicin 100 mg/m(2) plus docetaxel 75 mg/m(2).     

Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results.

PURPOSE: Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC. PATIENTS AND METHODS: Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2) on day 1 (n = 256). RESULTS: Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P =.0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P =.0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 30%, P =.006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination). CONCLUSION: The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2), with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2). Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.     

多西紫杉醇加表柔比星治疗局部晚期乳腺癌的多中心Ⅱ期临床研究

目的观察多西紫杉醇加表柔比星(ET方案)新辅助化疗方案治疗局部晚期乳腺癌(LABC)后的病理完全缓解率、客观缓解率、手术切除率以及毒性反应。方法2001年3至12月间共有40例IABC患者入组,中位年龄48(28～67)岁。Ⅲa期20例,Ⅲb期15例,单纯同侧锁骨上淋巴结转移5例。化疗剂量为表柔比星60mg/m^2,多西紫杉醇75mg／m^2,静脉点滴,每3周为1个周期。化疗中预防性应用粒细胞集落刺激因子(DCSF)。在2个周期ET方案之后,由研究者对病灶进行首次评估,以决定是否再给予1～2个周期ET后再接受手术或放射治疗。结果38例患者接受2～4个周期ET方案的新辅助化疗,病理完全缓解率、临床完全缓解率以及临床部分缓解率分别为15．0％、20．0％和52．5％。本组的手术切除率为92．5％。Ⅲ、Ⅳ度中性粒细胞减少症的发生率分别占总周期数的8.4％和14.0％,3例患者出现中性粒细胞减少性发热。常见的非血液系统不良反应为脱发、恶心或呕吐、体液潴留、肌肉关节疼痛以及指甲改变,但多呈轻、中度反应。结论多西紫杉醇联合表柔比星是针对LABC的一种安全而有效的新辅助化疗方案。     

Spotlight on Capecitabine in the Management of Advanced Breast Cancer

Capecitabine is an orally administered prodrug of fluorouracil which is indicated in the US and Europe, in combination with docetaxel, for the treatment of patients with metastatic breast cancer failing anthracycline therapy, and as monotherapy for metastatic breast cancer resistant to paclitaxel and anthracycline therapy (US) or failing intensive chemotherapy (Europe). Capecitabine is also approved for use in metastatic colorectal cancer. Capecitabine is metabolically activated preferentially at the tumor site, and shows antineoplastic activity and synergy with other cytotoxic agents including cyclophosphamide or docetaxel in animal models. Bioavailability after oral administration is close to 100%. In patients with pretreated advanced breast cancer, capecitabine is effective as monotherapy and also in combination with other agents. Combination therapy with capecitabine 1250 mg/m² twice daily for 2 weeks of every 3-week cycle plus intravenous docetaxel 75 mg/m² on day one of each cycle was superior to intravenous monotherapy with docetaxel 100 mg/m² on day one of each cycle. Capecitabine plus docetaxel significantly reduced the risks of disease progression and death by 35% (p = 0.0001) and 23% (p < 0.05), respectively, and significantly increased median survival (p < 0.05) and objective response rates (p < 0.01). Efficacy has also been demonstrated with capecitabine monotherapy and combination therapy in previously untreated patients in preliminary trials. The most common adverse effects occurring in patients receiving capecitabine monotherapy include lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, hyperbilirubinaemia, dermatitis and vomiting (all >25% incidence). While gastrointestinal events and hand-and-foot syndrome occurred more often with capecitabine than with paclitaxel or a regimen of cyclophosphamide, methotrexate and fluorouracil (CMF), neutropenic fever, arthralgia, pyrexia and myalgia were more common with paclitaxel, and nausea, stomatitis, alopecia and asthenia were more common with CMF. The incidence of adverse effects and hospitalization was similar in patients receiving capecitabine plus docetaxel and those receiving docetaxel monotherapy. In conclusion, capecitabine, an oral prodrug of fluorouracil which is activated preferentially at the tumor site, is an effective and convenient addition to the intravenous polychemotherapeutic treatment of advanced breast cancer in pretreated patients, and also has potential as a component of first-line combination regimens. Combined capecitabine plus docetaxel therapy resulted in similar rates of treatment-related adverse effects and hospitalization to those seen with docetaxel monotherapy. Capecitabine is also effective as monotherapy in pretreated patients and phase II data for capecitabine as first-line monotherapy are also promising. While gastrointestinal effects and hand-and-foot syndrome occur often with capecitabine, the tolerability profile was comparatively favorable for other adverse effects (notably, neutropenia and alopecia).     

Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study.

PURPOSE: The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-seven patients with MBC received oral capecitabine at 1650 mg/m(2)/d (825 mg/m(2) twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m(2) on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient' s decision to discontinue. Patients (35 to 76 years old) had a median Karnofsky performance status of 90%. Forty-four patients (94%) received study treatment as first-line therapy for metastatic disease. RESULTS: Objective responses occurred in 24 (51%) patients; seven (15%) complete responses and 17 (36%) partial responses. Stable disease lasting 180 days or more was observed in nine (19%); the clinical response rate was 70%. Median duration of response was 12.6 months, median time to disease progression was 10.6 months, and median overall survival time was 29.9 months. The most common treatment-related adverse events, regardless of severity, were alopecia, hand-foot syndrome, nausea, and fatigue. Neutropenia (15%), alopecia (13%), and hand-foot syndrome (11%) were the only grade 3 or 4 treatment-related adverse events that occurred in more than 10% of patients. CONCLUSION: The combination of capecitabine plus paclitaxel is a highly active and generally well-tolerated regimen for first-line treatment of MBC.     

多西紫杉醇联合希罗达治疗乳腺癌肺转移39例临床分析

目的 观察多西紫杉醇(紫杉特尔、Docetacel)联合希罗达治疗乳腺癌肺转移患者的临床疗效和不良反应,为临床治疗提供依据.方法 39例乳腺癌肺转移患者,用多西紫杉醇注射液75 mg/mz,第1天静脉滴注1小时,希罗达2 500 mg/m2,分早晚2次餐后半小时口服,第1-14天,21天为1个周期,连用4-6个周期.化疗前1天开始口服地塞米松8 mg,2次/天,连服3天,以防水钠潴留.每3周为1个周期,2个周期评价疗效.结果 39例患者完全缓解(CR)13例(33.3﹪),部分缓解(PR)14例(35.9﹪),总有效率(CR+PR)69.2﹪,稳定(SD)9例,进展(PD)3例.不良反应主要是骨髓抑制、胃肠道反应,对症治疗后均获得缓解,无化疗相关死亡.结论 多西紫杉醇联合希罗达治疗肺转移性乳腺癌有较好疗效,不良反应能耐受,是一种安全、有效的化疗方案.     

Primary systemic chemotherapy with sequential, dose-dense epirubicin and docetaxel for inoperable, locally advanced inflammatory breast cancer: a phase II study

Sequential, dose-dense epirubicin plus docetaxel was evaluated as primary systemic therapy for women with inoperable, locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients (LABC n=27; IBC n=7) received 3 cycles of epirubicin 120 mg/m2 every 2 weeks followed by 3 cycles of docetaxel 100 mg/m2 every 2 weeks, with granulocyte colony-stimulating factor. Grade 3-4 toxicities were observed in 21 of 195 cycles (10.8%). Grade 3 anemia and leukopenia each occurred in 1% of cycles. Following chemotherapy, all patients underwent surgery. Eight patients (23.5%) had a clinical complete response and 15 (44.1%) had a partial response. In patients with IBC, median skin thickness decreased from 5.85 mm (range: 3.1-6.2 mm) to 4 mm (range: 2.7-5.1 mm) (p<0.005). Sequential, dose-dense epirubicin plus docetaxel achieved a high response rate among patients with LABC or IBC with only moderate toxicity.     

Efficacy and tolerability of capecitabine with weekly paclitaxel for patients with metastatic breast cancer: a phase II report of the SAKK

BACKGROUND: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. PATIENTS AND METHODS: From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m(2) twice daily on days 1-14) plus i.v. paclitaxel (80 mg/m(2) on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. RESULTS: After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand-foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. CONCLUSION: The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation.     

卡培他滨联合多西紫杉醇一线治疗晚期胃癌的临床观察

目的 探讨卡培他滨联合多西紫杉醇一线治疗晚期胃癌的近期疗效、不良反应及生存情况。方法 2010年1月至2012年7月共24例晚期胃癌患者采用卡培他滨联合多西紫杉醇一线化疗,具体方案为：卡培他滨1000mg／m2口服,每天2次,d1～d14;多西紫杉醇75mg／m2静滴1h,d1,或者多西紫杉醇35mg／m2静滴1h,d1、d8。21天为1周期,至少化疗2个周期。2个周期评价疗效,每周期评价不良反应。结果 24例患者均可评价疗效。无CR病例,获PR 3例,SD 20例,PD 1例;有效率为12.5％,疾病控制率为95.8％。中位总生存时间为10.5个月（95％CI：2.47～18.47个月）;10例患者死于疾病进展,其中7例的疾病进展时间为1.7～15.2个月。主要不良反应为骨髓抑制和手足综合征,以1～2级为主,全组患者无治疗相关性死亡。结论 卡培他滨联合多西紫杉醇一线治疗晚期胃癌的疗效确切,不良反应可耐受,值得深入研究。     

多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床观察

目的:观察多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌的临床疗效及不良反应。方法:回顾性分析40例转移性乳腺癌患者的化疗资料,采用国产多西他赛75mg/m2,表柔比星70-90mg/m2静脉滴注,环磷酰胺500mg/m2每3周1次。观察每次化疗后的不良反应,完成4个疗程后观察疗效。结果:全部病例均按计划完成4个周期的化疗。完全缓解(CR)3例,部分缓解(PR)20例,稳定(SD)12例,进展(PD)5例。总有效率(CR+PR)为57.5%,控制率(CR+PR+SD)87.5%。主要不良反应为中性粒细胞减少、恶心、呕吐、腹泻等。结论:多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌临床疗效较好,不良反应患者可以耐受。     

Docetaxel 75 mg/m(2) is active and well tolerated in patients with metastatic or recurrent gastric cancer: a phase II trial

OBJECTIVE: The aim of the present study was to confirm the efficacy and tolerability of docetaxel 75 mg/m(2) in a population of Korean patients with advanced gastric cancer. METHODS: Patients with metastatic or locally recurrent gastric cancer received docetaxel 75 mg/m(2) by intravenous infusion every 3 weeks. Objective response rate was the primary endpoint. RESULTS: Forty-five patients were enrolled. Most showed adenocarcinomas of the gastric antrum and/or body of the stomach. All showed metastases and two-thirds retained the primary tumour. Forty-four patients received at least one docetaxel infusion ('treated' population), with 40 patients evaluable for response. A total of 159 cycles (median three cycles) were administered, with mean duration of treatment 10.9 weeks. The objective response rate in the treated population was 15.9% (17.5% in the per protocol population), with stable disease in 25.0% of patients and progressive disease in 50.0%. Grade 3-4 neutropenia occurred in 36 (81.8%) patients and 36.1% of cycles. However, febrile neutropenia occurred in only two (4.5%) patients and 1.3% of cycles. Grade 3 anorexia, experienced by two patients (4.5%) and during 1.9% of cycles, was the most frequent non-haematological adverse event possibly or probably related to docetaxel. No grade 4 non-haematological events occurred. CONCLUSION: This study suggests that docetaxel 75 mg/m(2) is active in metastatic or locally recurrent adenocarcinoma with a low incidence of grade 3-4 adverse events. Docetaxel warrants further study in combination regimens for advanced gastric cancer.     

Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study

Purpose In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated.Methods Epirubicin (75 mg/m²) and docetaxel (75 mg/m²) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC.Results The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7–12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure.Conclusions The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.     

Role of epirubicin in advanced breast cancer

Anthracyclines were first introduced for the treatment of metastatic breast cancer in the 1970s and are still among the most active single agents for the treatment of this disease. Unfortunately, their clinical value is limited by late-onset ventricular dysfunction. Epirubicin, an anthracycline analogue, does not eliminate the risk of cardiotoxicity but is less cardiotoxic and myelotoxic than doxorubicin at equimolar doses, thereby allowing the safe administration of cumulative doses between 950 and 1000 mg/m2. The inclusion of epirubicin in combination regimens, such as fluorouracil/epirubicin/cyclophosphamide (FEC), has been shown to be safe and active as first-line treatment for metastatic breast cancer. In the past few years, new drugs, including taxanes, have shown a high level of activity as single agents in the treatment of advanced breast cancer. Doxorubicin/paclitaxel combinations have shown high overall response rates (90%) as first-line chemotherapy of advanced breast cancer; however, congestive heart failure has been reported in up to 20% of patients. Epirubicin/paclitaxel combinations have been associated with grade 3 cardiotoxicity (6%) in only one study. We report findings of a trial of combination epirubicin/paclitaxel as first-line treatment of advanced breast cancer, with overall response rates (ORRs) of 84% and a complete response (CR) rate of 19%. Achieving a CR to first-line chemotherapy for advanced breast cancer appears to predict survival, and adding an active drug with a different mechanism of action and nonoverlapping toxicity might increase the percentage of CRs. We therefore tested the feasibility and activity of 6 to 8 courses of first-line treatment with a three-drug combination (gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1, and paclitaxel 175 mg/ m2 over 3 hours on day 1) in a phase II study of 36 metastatic breast cancer patients. Treatment was well tolerated, with an ORR of 92% (95% confidence interval: 77.53%-98.25%) and a CR of 31%. In considering retreating patients who progress or relapse after receiving an anthracycline-/taxane-containing regimen with the same active drugs, epirubicin appears ideal in both the adjuvant and metastatic breast cancer settings.