Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer.

PURPOSE: To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels. PATIENTS AND METHODS: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle. RESULTS: The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, 18 to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 44% to 80%). The ORR in patients whose tumors were HER-2-positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P =.04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing. CONCLUSION: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.     

Combination docetaxel and trastuzumab treatment for patients with her-2-overexpressing metastatic breast cancer: A multicenter, phase-II study

BACKGROUND: Pre-clinical and clinical studies indicate that a combination of docetaxel and trastuzumab may effectively treat patients with human epidermal growth factor receptor-2 (HER-2) overexpressing metastatic breast cancer. We evaluated the efficacy and safety of this combination in a multicenter, open-label phase II study in Japan. METHODS: Women with metastatic breast cancer whose tumors overexpressed HER-2, as assessed by immunohistochemistry and by fluorescence in situ hybridisation, received 2 to 6 cycles of docetaxel (70 mg/m2, every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). The primary endpoint was tumor response. Secondary endpoints were time to disease progression and adverse events. RESULTS: Of the 40 women enrolled in the study, 27 (68%) completed 6 cycles of treatment. Three patients discontinued the study before the second cycle. Median follow-up was 20.8 months (range, 0.6 to 30.9 months). The overall response rate was 65% (26/40; 95% CI, 48% to 79%). The median time to progression was 6.8 months (range, 0.6 to 21.2 months). Of the 40 patients, 35 (88%) had grade 3 or 4 leukopenia, and 33 (83%) had grade 3 or 4 neutropenia. Most instances of leukopenia and neutropenia were manageable by reducing the dose of docetaxel or by treatment with granulocyte colony-stimulating factor. In 4 patients, left ventricular ejection fraction decreased by more than 10% from baseline. CONCLUSIONS: The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.     

Efficacy and safety of combined trastuzumab and paclitaxel therapy as a second-line treatment in women with metastatic Breast Cancer: A single institutional experience

BACKGROUND: In breast cancer, HER-2 overexpression suggests s poor prognosis. Trastuzumab is a humanized monoclonal antibody with specificity to the HER-2 protein. We evaluated the safety and efficacy of combined trastuzumab and paclitaxel therapy in women with metastatic breast cancer. PATIENTS AND METHODS: Combination chemotherapy was given to patients with HER-2 overexpressing metastatic breast cancer. All patients had previously received one or more chemotherapy treatments. Patients received a loading trastuzumab dose of 4 mg/kg intravenously (i.v.), followed by 2 mg/kg maintenance dose at weekly intervals. A paclitaxel dose of 80 mg/m(2) was administered on the same day as the trastuzumab infusion. RESULTS: A total of 53 patients were examined. Seventy percent received two or more prior chemotherapy treatments for metastatic breast cancer, and 66.0% of patients had two or more metastatic sites. The overall response rate to our approach was 37.7%. Median time to progression was 12.0 months. Grade 3/4 neutropenia was seen in only 11.3% of patients. Peripheral neuropathy occurred in 65.1% of patients after seven treatments, requiring us to change to biweekly paclitaxel administration in 16 patients. Most of them were able to continue the treatment. Other toxicities were mild and tolerable. CONCLUSION: Combined trastuzumab and paclitaxel therapy, administered as second-line or later treatment, produced lasting objective responses and was well tolerated by women with HER-2 overexpressing metastatic breast cancer. A major obstacle to continuing treatment was peripheral neuropathy. However, modifying the interval to every 2 weeks enabled us to continue the treatment. This combination chemotherapy was safely performed in our outpatient clinic.     

Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer.

PURPOSE: To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab. PATIENTS AND METHODS: Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks. Responding patients received 8 additional weeks of trastuzumab (4 mg/kg/wk), and then proceeded to receive trastuzumab (2 mg/kg) in combination with paclitaxel 70 mg/m(2) and carboplatin (area under the curve, 2) weekly for 6 weeks followed by 2 weeks rest. Stable patients after the initial 8 weeks of trastuzumab proceeded to treatment with trastuzumab, paclitaxel, and carboplatin. Patients with disease progression during the initial 8 weeks had the trastuzumab discontinued and were treated with weekly paclitaxel/carboplatin. RESULTS: Weekly paclitaxel/carboplatin with or without trastuzumab was well tolerated. Fifty-two patients were assessable for response and all 61 patients were assessable for survival. Seventeen (33%) of 52 patients experienced a minor/partial response to single-agent trastuzumab and received 8 additional weeks of single-agent trastuzumab. Fifteen (29%) of 52 patients had stable disease and proceeded to receive paclitaxel/carboplatin/trastuzumab. Thirty-one patients with measurable disease were assessable for response after initial single-agent trastuzumab followed by paclitaxel/carboplatin/trastuzumab. An overall response rate of 84% (eight complete responses/18 partial responses), median time to progression of 14.2 months, and median overall survival of 32.2 months was reported with the triplet combination. In the patients treated with paclitaxel/carboplatin alone after disease progression on initial single-agent trastuzumab, an overall response rate of 69% (one complete response/10 partial responses), median time to progression of 8.3 months, and median overall survival of 22.2 months was reported. Median time to progression for all 61 patients is 10 months and the median overall survival is 26.7 months. CONCLUSION: This trial confirms the activity and tolerability of weekly paclitaxel/carboplatin alone or in combination with trastuzumab in women with HER-2 overexpressing metastatic breast cancer.     

Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study

We conducted a pilot phase II trial of trastuzumab administered concurrently with docetaxel in women with HER2-overexpressing advanced breast cancer. Twenty-five women with HER2-positive (3+ by immunohistochemistry = 16, 2+ = 9) metastatic breast cancer received docetaxel (75 mg/m every 3 weeks for 6 cycles) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-three patients (92%) had visceral metastatic involvement. Twenty-three patients had received prior chemotherapy as part of adjuvant (18), metastatic (2), and both (3) treatment. The number of cycles administered was 121 (median 6, range 1-6). Symptomatic cardiotoxicity (GIII) occurred in one patient. The most common grade GIII/IV toxicity was neutropenia (80% of the cycles), although febrile neutropenia did not occur. No other GIII/IV toxicities were observed. Response rate was 70% (1 complete response and 15 partial responses) in 23 evaluable patients. The combination of docetaxel and trastuzumab is well tolerated and has clinically meaningful antitumor activity.     

Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results

Trastuzumab/chemotherapy combinations have already shown superior results in metastatic breast cancer patients. The purpose of this study is to determine the clinical efficacy of neoadjuvant trastuzumab and docetaxel in women with locally advanced breast cancer, with or without metastatic disease. Treatment-naive women with HER2-overexpressing locally advanced breast cancer, with or without metastatic disease, were included. Patients received trastuzumab 4 mg/kg loading dose intravenously then 2 mg/kg weekly. On day 22, docetaxel 100 mg/m2 every 3 weeks for 4 cycles was added to weekly trastuzumab. Patients then underwent surgery and subsequent 4 cycles of AC (doxorubicin/cyclophosphamide; 60/600 mg/m2) without trastuzumab. Weekly trastuzumab was resumed 1 month after completion of AC and continued for a year. Preliminary results from the first 22 patients with median follow-up of 15.5 months (range, 2-38 months) are reported. Of these, 9 patients (40.9%) had inflammatory breast cancer, and 6 patients (27.3%) had stage IV breast cancer. Seventeen of 22 patients (77.3%) had objective clinical response, with a clinical complete response in 9 patients (40.9%). Two patients (9.1%) had decline in cardiac function and 7 patients (31.8%) experienced neutropenia, with 2 deaths (9.1%) from neutropenic sepsis. Eight patients (36.4%) have relapsed, 3 with local skin recurrence (13.6%) and 5 with distant recurrence, of whom 1 had liver metastasis (4.5%) and 4 had brain metastasis (18.2%). Combined neoadjuvant trastuzumab and docetaxel induced high clinical response rates for HER2-overexpressing breast cancer, in particular for inflammatory breast cancer. A high rate of brain metastasis was noted, particularly in patients with baseline metastatic disease.     

曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性

目的:观察曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性。方法:这是一项前瞻、单臂、开放标签的单中心Ⅱ期临床研究(ChiCTR1800015814)。HER-2阳性晚期乳腺癌一线治疗给予曲妥珠单抗(6 mg/kg,首剂8 mg/kg)联合拉帕替尼(1 000 mg/d)及多西紫杉醇(75 mg/m2),每3周重复。对非进展的患者继续用药直至疾病进展或毒性不可耐受,但最长用药时间不超过2年。主要研究终点是有效率,次要终点是PFS和OS。结果:自2016年9月至2019年5月共入组65例患者。本方案的剂量限制性毒性为腹泻,Ⅲ-Ⅳ度腹泻发生率为24.6%。总体有效率为69.2%(CR 3.1%,PR 66.1%),激素受体阴性患者有效率明显优于激素受体阳性患者(76.7% vs 57.1%,P＜0.01)。中位随访31个月,PFS为16.4个月(95%CI:13.4~19.6个月)。尚未达到中位OS时间。Log-rank检验显示是否内脏转移、是否多器官转移对PFS的影响具有统计学意义(P＜0.01和P=0.022)。结论:曲妥珠单抗联合拉帕替尼及多西紫杉醇毒性可耐受,疗效较好,作为HER-2阳性晚期乳腺癌一线治疗新的治疗策略,值得进一步研究。     

曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效和不良反应

背景与目的:大约有20%～30%的乳腺癌患者Her-2/neu高表达,Her-2/neu高表达与患者的不良预后密切相关.化疗药物联合曲妥珠单抗可以显著提高Her-2/neu高表达乳腺癌患者的化疗有效率和生存率,多西紫杉醇是近年来治疗乳腺癌有效的化疗药物之一.本研究旨在观察曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效与不良反应.方法:22例Her-2/neu高表达转移性乳腺癌患者接受曲妥珠单抗联合多西紫杉醇方案治疗,曲妥珠单抗的首次剂量为8 mg/kg,以后的剂量为6 mg/kg.多西紫杉醇75mg/m2,每21 d重复一次.按WHO疗效评价标准评价疗效,按WHO化疗药物急性和亚急性不良反应评价标准评价不良反应.结果:全组22例患者共完成96个周期化疗(中位数3周期,范围2～6周期),所有患者均可评价疗效.22例患者中完全缓解2例,部分缓解12例,病情稳定4例,病情进展4例,客观有效率(CR PR)63.64%,中位疾病进展时间5.4个月,1年生存率59%.全组患者均可评价不良反应,主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度白细胞减少发生率为54.5%,部分患者有发热(第一次输注曲妥珠单抗时出现)和轻度的心肌劳损.结论:曲妥珠单抗联合多西紫杉醇方案治疗Her-2/neu高表达转移性乳腺癌近期疗效较高,不良反应轻,患者可以耐受.     

Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure

This multicentre, randomised phase III study compared docetaxel with 5-fluorouracil+vinorelbine in patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy. One hundred and seventy-six metastatic breast cancer patients were randomised to receive docetaxel (100 mg m(-2)) every 3 weeks or 5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m(-2) per day continuous infusion) D1-5 plus vinorelbine (25 mg m(-2)) D1 and D5 of each 3-week cycle. Eighty-six patients received 516 cycles of docetaxel; 90 patients received 476 cycles of 5-fluorouracil+vinorelbine. Median time to progression (6.5 vs 5.1 months) and overall survival (16.0 vs 15.0 months) did not differ significantly between the docetaxel and 5-fluorouracil+vinorelbine arms, respectively. Six (7%) complete responses and 31 (36%) partial responses occurred with docetaxel (overall response rate 43%, 95% confidence interval: 32-53%), while 4 (4.4%) complete responses and 31 (34.4%) partial responses occurred with 5-fluorouracil+vinorelbine (overall response rate 38.8%, 95% confidence interval: 29-49%). Main grade 3-4 toxicities were (docetaxel vs 5-fluorouracil+vinorelbine): neutropenia 82% vs 67%; stomatitis 5% vs 40%; febrile neutropenia 13% vs 22%; and infection 2% vs 7%. There was one possible treatment-related death in the docetaxel arm and five with 5-fluorouracil+vinorelbine. In anthracycline-pretreated metastatic breast cancer patients, docetaxel showed comparable efficacy to 5-fluorouracil+vinorelbine, but was less toxic.     

A phase II study of three-weekly docetaxel and weekly trastuzumab in HER2-overexpressing advanced breast cancer

BACKGROUND: To test safety and activity of 3-weekly doses of docetaxel and a weekly dose of trastuzumab in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty-two women, median age 53 years (range 36-73 years), with HER2-overexpressing advanced breast cancer were enrolled in a study of docetaxel, 75 mg/m(2) q3w for 6 cycles, and trastuzumab, 4 mg/kg loading dose, 2 mg/kg weekly thereafter. Thirty-four patients (81%) had visceral metastatic involvement. Thirty-five patients had received prior chemotherapy as part of their treatment: adjuvant/neoadjuvant (26), metastatic (2) and both (7). Thirty-one patients had been previously exposed to an anthracycline and 11 to paclitaxel. Four patients had previously received high-dose chemotherapy followed by autologous stem cell transplant. RESULTS: 226 cycles (median 6, range 1-6) were administered. The median delivered dose intensity for docetaxel was 24 mg/m(2)/week (range 16-25 mg/m(2)/week). The intent to treat overall response rate was 67% (95% confidence interval, 52-79%). Median progression-free survival, time to treatment failure, and duration of response were 9, 8 and 12 months, respectively. Symptomatic cardiotoxicity (grade 3) occurred in 1 patient. The most common grade 3/4 toxicity was neutropenia (76% of the patients), although febrile neutropenia did not occur. CONCLUSIONS: Three-weekly doses of docetaxel and a weekly dose of trastuzumab is an active and safe combination in patients with HER2-overexpressing advanced breast cancer.     

Study of three-weekly docetaxel and weekly trastuzumab treatment in HER 2-overexpressing metastatic breast cancer patients

Docetaxel and trastuzumab can be considered to be active drugs for HER 2-overexpressing metastatic breast cancer (MBC). This study was conducted to determine the activity of combination therapy with docetaxel and trastuzumab in MBC patients (pts) by assessing the response rate (RR), time to progression (TTP) and safety. We administered the combination of docetaxel 70 mg/m2 every 3 weeks and trastuzumab using a 4 mg/kg loading dose and thereafter 2 mg/kg weekly. One cycle was three weeks. Between March 2002 and May 2003, 40 pts with HER 2-positive (3+by immunohistochemistry 39, FISH+1) MBC were enrolled in this study, and 39 pts proved eligible. The overall RR was 72% (28/39) [95%CI 55.1%-85.0%], with 6 CR, 22 PR, 7 SD, 1 PD and 3 NE. The median follow-up time was 14.3 months, while the TTP was 6.5 months (range, 0.6-19.8), median OS has not yet been reached. The number of pts assessable for safety was 40. Hematological Grade 3-4 toxicities were leukopenia 87.5% (35/40) and neutropenia 82.5% (33/40). Non-hematological Grade 3 toxicities were weight gain in 2 pts, and anorexia, neuropathy, fever and rash in one pt each. The combination of docetaxel and trastuzumab was a well-tolerated and very active regimen for the treatment of pts with HER 2-overexpressing MBC.     

Phase II study of weekly docetaxel alone or in combination with trastuzumab in patients with metastatic breast cancer

This study was designed to determine the efficacy and toxicity of weekly docetaxel in metastatic breast cancer when given alone (for HER2/neu negative disease) or with trastuzumab (for HER2/neu overexpressing disease). Patients with metastatic breast carcinoma received docetaxel given on 2 different schedules (group 1A, 33 mg/m2 weekly [n = 21]; group 1B, 40 mg/m2 weekly for 3 weeks with 1 week off [n = 14]). Patients with HER2/neu overexpressing disease also received trastuzumab 4 mg/kg on day 1, then 2 mg/kg on days 8 and 15 of each 28-day cycle (group 2). Fifty-two patients were treated with docetaxel alone (group 1A/B, n = 35) or in combination with trastuzumab (group 2, n = 17). Prior taxane therapy given every 3 weeks had been used for metastatic disease in 19 of 35 patients (54%) in group 1A/B and in 2 of 17 patients (12%) in group 2. The mean delivered dose intensity of docetaxel was 29 mg/m2 per week. Partial response occurred in 7 of 35 patients (21%; 95% exact binomial confidence interval [CI], 9%-38%) treated with docetaxel alone, including 3 of 19 taxane-pretreated patients (16%) and 4 of 16 taxane-naive patients (25%). Partial response occurred in 10 of 17 patients (59%; 95% CI, 34%-82%) treated with docetaxel/trastuzumab. The most common grade 3/4 toxicities, occurring in more than or equal to 10% of patients, included neutropenia (21%), pulmonary toxicity (12%), and hyperglycemia (10%). The median times to disease progression were 4.5 months (95% CI, 2.5-6.5 months) in the docetaxel group and 8.5 months (95% CI, 4.5-12.5 months) in the docetaxel/trastuzumab group. Weekly docetaxel/trastuzumab is an effective regimen for patients with HER2/neu overexpressing metastatic breast cancer. Weekly docetaxel may be effective in as many as 20% of patients who had progressive disease after treatment with taxanes given every 3 weeks.     

Biweekly docetaxel and weekly trastuzumab treatment in HER 2-overexpressing metastatic breast cancer patients

Docetaxel and trastuzumab can be considered to be active drugs for HER 2-overexpressing metastatic breast cancer (MBC). This study was conducted to determine the activity of combination therapy with docetaxel and trastuzumab in MBC patients by assessing the response rate (RR), time to progression (TTP) and safety. We administered the combination of docetaxel 30-40 mg/m(2) biweekly and trastuzumab using a 4 mg/kg loading dose and thereafter 2 mg/kg weekly. Between October 2001 and December 2004, 14 patients with HER 2 positive (3+ by immunohistochemistry) MBC were enrolled in this study. The overall RR was 50.0% (7/14), with 1 CR, 6 PR, 3 NC and 4 PD. Median follow-up time was 15.0 months, while the median TTP was 10.8 months,and the median OS 21.8 months.     

Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results

Preliminary results of a phase II study of gemcitabine plus trastuzumab in previously treated (up to 3 previous regimens) metastatic breast cancer patients are presented. Patients had histologically confirmed metastatic breast cancer, with 2+ or 3+ tumor HER2 expression. Treatment consisted of gemcitabine 1200 mg/m2 over 30 minutes intravenously on days 1 and 8 every 21 days, and trastuzumab 4 mg/kg over 90 minutes, followed by 2 mg/kg infused over 30 minutes weekly. Treatment was continued until disease progression or unacceptable toxicity occurred. Preliminary results are available on the first 38 patients enrolled. Median patient age was 53 years, 53% had estrogen receptor/progesterone receptor-positive disease, and HER2 staining was 2+ in 39% and 3+ in 61% of patients. There was a median of 3 previously administered (including adjuvant) chemotherapy regimens, and a median of 4.5 treatment cycles per patient has been administered so far. Twelve patients (32%) have had an objective partial response, with a median response duration of 8.6 months. Median time to disease progression is 6.7 months to date, with a median overall survival of 10.2 months. No unexpected toxicities or grade 4 nonhematologic toxicities have been observed; 2 patients developed grade 4 neutropenia and 1 patient had febrile neutropenia. Thus, gemcitabine/ trastuzumab resulted in an encouraging 32% response rate, given the heavily pretreated patient population. Tolerability was good overall, with no unexpected side effects observed.     

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.

PURPOSE: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients were randomly assigned to six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. RESULTS: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. CONCLUSION: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.     

曲妥珠单抗联合紫杉醇脂质体和卡培他滨治疗HER-2阳性复发转移性乳腺癌

目的：评估曲妥珠单抗（trastuzumab,H）与紫杉醇脂质体（paclitaxel liposome,P）、卡培他滨（capecit-abine,X）的联合方案HPX方案治疗人表皮生长因子受体-2（human epidermal growth factor receptor-2,HER-2）阳性复发转移性乳腺癌的疗效与安全性。方法筛选HER-2阳性复发转移性乳腺癌患者32例,给予HPX方案治疗：曲妥珠单抗首次8 mg／kg,后6 mg／kg维持,d1;紫杉醇脂质体175 mg／m2,d1;卡培他滨825 mg／m2,2次／d,d1－14,21天为1周期。结果32例患者中位无进展生存时间（progression-free survival,PFS）为12．7月（95％CI：5．7－19.7月）,客观缓解率（objective response rate,ORR）为53．2％,临床获益率（clinical benefit rate,CBR）为84．5％。一线治疗患者的PFS达15．3月（95％ CI：2．5－28．1月）,ORR达68．4％,CBR达84．2％。Ⅲ～Ⅳ级不良反应主要为血液学毒性,包括中性粒细胞减少（46．9％）、白细胞减少（37．5％）、血小板减少（6．3％）,Ⅲ～Ⅳ级非血液学不良反应主要为手足综合征（9．4％）和腹泻（3．1％）。结论曲妥珠单抗联合紫杉醇脂质体和卡培他滨是治疗HER-2阳性复发转移性乳腺癌的有效治疗方案,且安全性良好。     

曲妥珠单抗联合含长春瑞滨方案治疗人表皮生长因子受体2阳性晚期乳腺癌的研究

目的观察曲妥珠单抗联合长春瑞滨方案治疗人表皮生长因子受体2（HER-2）阳性晚期乳腺癌的疗效及安全性。方法收集中国医学科学院肿瘤医院2001年2月至2012年2月期间应用曲妥珠单抗联合含长春瑞滨化疗方案治疗的55例晚期乳腺癌患者的临床资料。回顾性分析其临床特点、药物疗效、不良反应及生存状况。结果应用曲妥珠单抗联合含长春瑞滨方案治疗的55例患者中,完全缓解（CR）2例,部分缓解（PR）24例,疾病稳定（SD）16例,疾病进展（PD）13例,总有效率为47.3%,疾病控制率为76.4%,中位PFS为8.0个月。患者中位生存时间为46.1个月,1年生存率为95.8%,2年生存率为76.8%,5年生存率为45.7%。3例心悸考虑为曲妥珠单抗相关的不良反应,患者未出现明显心功能不全。不良反应主要为化疗药物导致的血液学毒性和非血液学毒性。结论曲妥珠单抗联合含长春瑞滨方案治疗HER-2阳性的晚期乳腺癌疗效肯定,毒性可耐受。     

Safety and efficacy of trastuzumab every 3 weeks combined with cytotoxic chemotherapy in patients with HER2-positive recurrent breast cancer: findings from a case series

BACKGROUND: Trastuzumab has been repeatedly shown to result in significant clinical benefits and was subsequently accepted as the treatment of choice for HER2-positive advanced breast cancer - particularly as first-line treatment in combination with taxanes and as monotherapy in the second-line or third-line setting. Trastuzumab is currently licensed as a weekly treatment, although a 3-weekly schedule could be used conveniently in combination with other cytotoxic agents that are administered on a 3-weekly basis in metastatic breast cancer. PATIENTS AND METHODS: We determined the safety of i.v. trastuzumab (8 mg/kg followed by 6 mg/kg) every 3 weeks in combination with chemotherapeutic agents administered in 3-weekly courses (docetaxel, vinorelbine and capecitabine) in 31 patients with HER2-positive recurrent locoregional and/or metastatic breast cancer. RESULTS: 3-weekly trastuzumab appeared to be as well tolerated as the standard once-weekly schedule. All myelosuppressive adverse events and the majority of non-hematological adverse events were typical and characteristic of the individual concomitant cytotoxic agents. Transient trastuzumab-related infusion reactions occurred in 5 patients and 1 patient developed cardiac dysfunction, which recovered after discontinuation of trastuzumab. Efficacy appeared favourable: 18 clinical responses (3 complete and 15 partial) and 8 disease stabilizations gave an overall response rate of 58% (70% in the 20 patients receiving first-line therapy). Median progression-free and overall survival times were 9.9 months (95% CI: 6.3-13.5) and 23.1 months (95% CI: 19.2-27.0), respectively. CONCLUSIONS: These findings will likely encourage further evaluation of this more convenient 3-weekly trastuzumab regimen in patients with HER2-positive metastatic breast cancer.     

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+.     

Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.

PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. RESULTS: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. CONCLUSION: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.