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.     

A phase II feasibility trial of dose-dense docetaxel followed by doxorubicin/cyclophosphamide as adjuvant or neoadjuvant treatment for women with node-positive or high-risk node-negative breast cancer

PURPOSE: Dose-dense adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel has improved results compared with standard dosing at 3-week intervals. Because docetaxel might be more active than paclitaxel in the treatment of metastatic breast cancer, we explored the feasibility of substituting docetaxel for paclitaxel in dose-dense adjuvant therapy. PATIENTS AND METHODS: Seventy-six patients with node-positive breast cancer received treatment with 4 cycles of docetaxel followed by 4 cycles of AC administered with pegfilgrastim at 2-week intervals. When treatment proved difficult for the first 33 patients, 2 additional cohorts were treated: first, with a reduction of pegfilgrastim and dexamethasone prophylaxis doses (cohort 2) and then with a reduction of docetaxel from 100 mg/m2 to 75 mg/m2 (cohort 3). RESULTS: Treatment with dose-dense docetaxel at 100 mg/m2 resulted in unacceptable toxicity (24% of patients required hospitalization) and compromised subsequent dosing of AC as a result of neutropenia on the day of scheduled treatment. Only 21 patients (40%) who received docetaxel 100 mg/m2 were able to receive all 8 doses at full dose and on schedule. Reduction of docetaxel to 75 mg/m2 allowed 74% of patients to receive all 8 doses as scheduled. Delivery of AC as scheduled occurred in 82% of patients who received docetaxel 75 mg/m2 versus 40% when docetaxel 100 mg/m2 was administered. CONCLUSION: Full-dose docetaxel is difficult to administer as part of this dose-dense treatment regimen. Docetaxel 75 mg/m2 can be administered with improved subsequent delivery of 4 courses of dose-dense AC. Until comparative clinical studies are available, docetaxel should not be substituted for paclitaxel in dose-dense adjuvant chemotherapy for patients with high-risk breast cancer.     

Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer.

PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.     

Docetaxel plus epidoxorubicin as neoadjuvant treatment in patients with large operable or locally advanced carcinoma of the breast: a single-center, phase II study

BACKGROUND: The objective of this study was to test the activity and toxicity of epirubicin plus docetaxel as primary chemotherapy for women with large, operable (T2; > 3 cm) or locally advanced (Stage III) breast carcinoma, including patients with inflammatory breast carcinoma. METHODS: In this single-center, open-label, single-stage, Phase II trial, epirubicin (75 mg/m(2); intravenous bolus) followed by docetaxel (80 mg/m(2); 1-hour intravenous infusion) was administered on Day 1 of each cycle for four cycles. RESULTS: Nine of 30 patients (30%) had inflammatory breast carcinoma. Twenty-three patients (76.7%; 95% confidence interval, 57.7-90.1) had a clinical objective response that was complete in 6 patients (20%). Twenty-seven patients (90%) underwent surgery that was conservative in 5 patients (16.7%). Pathologic response evaluation revealed four complete responses (13.3%; 95% confidence interval, 3.8-30.7). Grade 4 neutropenia was recorded in 80.0% of patients, and febrile neutropenia was recorded in one-third of patients. Anemia and thrombocytopenia were never severe. Other side effects were diarrhea (26.6%), oral mucositis (43.3%), and emesis (26.6%). CONCLUSIONS: Neoadjuvant chemotherapy with epirubicin plus docetaxel was a feasible treatment and was active in an unfavorable series of patients with locally advanced breast carcinoma, including patients with inflammatory breast carcinoma.     

Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer

Currently, randomized phase III trials have demonstrated that docetaxel is an effective strategy in the adjuvant treatment of breast cancer. However, previous attempts to incorporate docetaxel with an anthracycline in a dose-dense regimen have been unsuccessful. Therefore, new schedules containing both drugs should be explored. Forty-four patients with high-risk operable breast cancer entered this feasibility study. They were treated with three cycles of epirubicin 110 mg/m2 every 2 wk with G-CSF followed by three cycles of "intensified" CMF (840 mg/m2 cyclophosphamide; 57 mg/m2 methotrexate; 840 mg/m2 fluorouracil) every 2 wk with G-CSF followed 3 wk later by nine weekly cycles of 35 mg/m2 docetaxel (E-CMF-doc). Totally, 39 patients (89%) received all cycles of chemotherapy. The vast majority (92%) of cycles were administered at full dose. Therefore, dose intensity was sufficiently maintained for all drugs. Toxicity was generally mild to moderate. Most frequently recorded side effects apart from alopecia were neutropenia (54%) and nausea/vomiting (89%). Infection developed in nine patients. Two cases of febrile neutropenia were reported. The E-CMF-doc regimen, as used in this study, is feasible and well tolerated. Its impact on survival should be evaluated in phase III trials.     

Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study

PURPOSE: In order to evaluate the feasibility of dose-dense docetaxel followed by dose-dense AC (doxorubicin/cyclophosphamide) as adjuvant chemotherapy for operable breast cancer, we conducted a phase II study. PATIENTS AND METHODS: In cohort 1, 28 patients received docetaxel 100 mg/m2 followed by doxorubicin 60 mg/m2 with cyclophosphamide 600 mg/m2, each every 2 weeks for 4 weeks (total of 8 cycles). Enrollment was discontinued because of stopping criteria based on significant toxicity (grade 4 hematologic toxicity or grade >or= 3 nonhematologic toxicity). In cohort 2, the docetaxel dose was reduced to 75 mg/m2; enrollment was discontinued after 18 patients. RESULTS: Significant toxicity occurred in 79% and 72% of patients in cohorts 1 and 2, respectively, resulting in treatment delays in 50% and 17% of patients, respectively. The most common grade 4 hematologic toxicity was neutropenia, which occurred in 7% and 42% of cohort 1 patients during docetaxel and AC, respectively, and in none and 19% of cohort 2 patients, respectively. The most common grade >or= 3 nonhematologic toxicity was palmar-plantar erythrodysesthesia, which occurred in 25% and none of cohort 1 patients during docetaxel and AC, respectively. With docetaxel 75 mg/m2 and patient education encouraging routine use of topical strategies, grade 3 palmar-plantar erythrodysesthesia occurred in only 11% of cohort 2 patients. Grade 2 nail changes were also debilitating and occurred in 33% of cohort 1 patients during AC. CONCLUSION: These phase II findings suggest that dose-dense docetaxel 100 mg/m2 followed by AC is not feasible and, until more studies are conducted, should be restricted to clinical studies.     

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.     

A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer

The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.     

A phase II trial of capecitabine and docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer

BackgroundCapecitabine (X) and docetaxel (T) have demonstrated a synergistic effect in preclinical models and a survival benefit in metastatic breast cancer. This study's purpose was to determine the efficacy of X and T followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting.Patients and methodsPatients with stage II/III breast cancer received four cycles of XT (capecitabine 1650 mg/m² on days 1–14 and docetaxel 60 mg/m² on day 8 every 3 weeks), followed by four cycles of FEC (5-fluorouracil 500 mg/m², epirubicin 90 mg/m², and cyclophosphamide 500 mg/m² on day 1 every 3 weeks). Primary end points were the pathological complete response (pCR) rate and adverse drug reactions.ResultsSeventy-four patients were enrolled and 71 patients were assessable for clinical and pathological responses. The overall response rate was 91.5%. The pCR rate was 14.1% (10 of 71). Grade 3/4 neutropenia was observed in 32.4% of patients. The most common grade 3/4 non-hematologic adverse event was hand–foot syndrome, observed in 11.3% of patients. With 29 months median follow-up, 2-year disease-free survival was estimated 85% for all patients.ConclusionThese data indicate that the sequential combination of XT followed by FEC is a well-tolerated, effective neoadjuvant treatment of stage II/III breast cancer.     

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。     

EC序贯P剂量密集方案与TEC方案在乳腺癌新辅助化疗中的疗效比较

目的 比较EC序贯P剂量密集方案与TEC方案在乳腺癌新辅助化疗中的疗效和不良反应。 方法 对2011年2月至2012年8月收治的64例Ⅱa期～Ⅲc期乳腺癌新辅助化疗患者进行回顾性分析,根据化疗方案分为剂量密集组（31例）和TEC组（33例）,术前分别接受3～8个周期EC序贯P剂量密集方案和2～6个周期TEC方案新辅助化疗。密集方案：E（表阿霉素）90 mg／m2 d1,联合C（环磷酰胺）600 mg／m2 d1,每14天为1周期,共4个周期,序贯至P（紫杉醇）175 mg／m2d1,每14天为1周期,共4个周期。TEC方案：T（多西紫杉醇）75 mg／m2d1,E 70 mg／m2 d1,C 600 mg／m2d1,每21天为1周期。按照实体瘤的疗效评价标准（RECIST）1.1和术后病理组织学 结果 评定疗效,按照不良事件常用术语评定标准4.0版（CTCAE 4.0）评价不良反应。 结果 全组64例患者均可评价疗效。剂量密集组和TEC组的病理完全缓解率分别为16.1％和12.1％,有效率分别为80.6％和66.7％,两组的病理完全缓解率和有效率的差异无统计学差异（P＞0.05）;剂量密集组和TEC组的1、2年无病生存率分别为93.5％、86.7％和93.9％、81.8％, 1、2年总生存率分别为100.0％、90.3％和100.0％、85.8％,且两组无病生存率和总生存率的差异均无统计学差异（P＞0.05）;TEC组3～4级中性粒细胞下降的发生率高于剂量密集组（6.4％ vs. 33.3％,P=0.012）,剂量密集组1～2级神经毒性（80.6％ vs. 36.4％,P＜0.001）和肌肉关节酸痛（67.7％ vs. 30.3％,P=0.005）的发生率均高于TEC组。 结论 剂量密集EC序贯P新辅助化疗方案与TEC方案疗效相似,毒副反应可以耐受,但安全性更好,有延长无病生存期和总生存期的趋势,是新辅助化疗的优选方案。     

A phase II study of neoadjuvant docetaxel plus doxorubicin (KBCS-01) in stage II, III breast cancer

SummaryBackground This multicenter phase II study was conducted to evaluate the response and safety of a combination of docetaxel plus doxorubicin as neoadjuvant therapy for stage II, III breast cancer.Methods Patients with stage II or III breast cancer underwent three cycles of neoadjuvant chemotherapy with doxorubicin 50 mg/m² and docetaxel 75 mg/m² every 3 weeks followed by curative surgery. Prophylactic GCSF was not used.Results Ninety patients were enrolled in the study and 86 were evaluable for efficacy. The median age was 43 years (range, 30–69). The mean relative dose intensity was 0.98 for docetaxel and 0.98 for doxorubicin. Breast-conserving surgery was performed in 12 (13.7%) patients. The clinical overall response rate was 86% and pathologic complete response was 10.5%. Grade 3/4 neutropenia was observed in 26% of total 258 cycles and febrile neutropenia was observed in 15.8%. Pneumonia was observed in one patient and grade 3 mucositis was observed in three patients.Conclusion Docetaxel and doxorubicin was an effective and well-tolerated neoadjuvant chemotherapy for stage II and III breast cancer. Clinical benefit of this treatment will be confirmed by survival data with long term follow up.     

Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival

Purpose This multicenter phase II study examined the impact of pathological effect on survival after preoperative chemotherapy in Japanese women with early stage breast cancer. Patients and methods Prior to surgery, patients received four cycles of FEC (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2) q3w) followed by four cycles of docetaxel (75 mg/m(2) q3w). Primary endpoint was 3 year disease free survival (DFS) stratified by the absence or presence of Quasi-pCR (QpCR; absence of invasive tumor or only focal residual tumor cells). Secondary endpoints were predictors for QpCR, clinical response, breast conservation rate, and safety. Results Between June 2002 and June 2004, 202 women were enrolled. Among 191 assessable patients, 25% achieved QpCR. With 40 months median follow-up, 3 year DFS was estimated at 91% for all patients. 3 year DFS for patients with QpCR was 98% vs. 89% without QpCR (hazard ratio 0.38 [95% Confidence Interval 0.09-0.84], P = 0.0134). HER2 status and response to FEC were independent predictors of QpCR. The overall clinical response was 75%; 85% of patients achieved breast conservation. Grade 3/4 neutropenia was the most common adverse event, observed in 44% and 35% of patients during FEC and docetaxel, respectively. Treatment related side effects were manageable; there were no treatment related fatalities. Conclusion FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer. QpCR following preoperative chemotherapy predicts favorable DFS. HER2 overexpression and clinical response to FEC predict QpCR.     

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.     

Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy

An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.     

Neoadjuvant docetaxel and capecitabine and the use of thymidine phosphorylase as a predictive biomarker in breast cancer.

PURPOSE: Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. EXPERIMENTAL DESIGN: Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m(2) i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). RESULTS: The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. CONCLUSIONS: DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.     

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

This study was designed to evaluate the efficacy and tolerability of a weekly schedule of epirubicin in combination with docetaxel in the first-line treatment of patients with metastatic breast cancer (MBC). A total of 43 women with MBC not previously treated with chemotherapy for metastatic disease received weekly epirubicin 25 mg m(-2) and docetaxel 25 mg m(-2) for a maximum of five cycles (total cumulative epirubicin dose of < or =900 mg m(-2)). Dose reduction was not permitted. Objective response and evaluation of toxicity profile were the primary study end points; time to progression and overall survival were secondary end points. Patients were followed for a median of 21 (4-38) months. Analysis was by intent to treat; 33 patients completed five cycles of therapy, and the median dose of epirubicin administered to the 43 patients was 23 mg m(-2). Twenty-five patients (58%) achieved a partial response and one (2%) achieved a complete response. An additional 12 patients (28%) had stable disease. The median time to progression was 11 months (95% confidence intervals (CI) 7-14) overall, and 13 months (95% CI 12-14) in the 26 patients who responded to treatment. Median overall survival was 25 months for responders and 14 months for nonresponders. Grade 3/4 neutropenia occurred in 16% of patients and in 6% of cycles. One patient developed cardiac toxicity (20% reduction in left ventricular ejection fraction). The combination of epirubicin plus docetaxel is highly active in MBC, with a manageable toxicity profile. Such a weekly schedule might provide a valuable treatment option for MBC.     

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.     

High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer

On the basis of preclinical and clinical data, we designed a phase II study to determine the efficacy and feasibility of high-dose epirubicin plus docetaxel (Taxotere) with lenograstim support, as first-line therapy for patients with advanced breast cancer. Patients with histologic evidence of metastatic breast cancer, without previous chemotherapy, adequate organ functions, Eastern Cooperative Oncology Group performance status less than 2, and signed informed consent entered in the trial. Treatment consisted of premedication the day before the treatment day for 3 consecutive days (dexamethasone 16 mg o.r. and 5-HT3 antagonists). On the treatment day 1, epirubicin 130 mg/m2 was administered as a 15-minute intravenous infusion followed 1 hour later by 1-hour intravenous infusion of docetaxel 100 mg/m2. Cycles were repeated every 21 days, for a maximum of 8 cycles. Lenograstim (5 microg/kg, s.c.) was started 48 hours later (day 4) and was given daily for 10 consecutive days. Response evaluation was made after the third cycle was applied, following World Health Organization criteria. Responding patients received five additional cycles. Median time to progression and survival were calculated according to the Kaplan-Meier method. A total of 32 patients have been included in the study. A total of 236 courses were delivered. A total response rate of 87.5% (95% confidence interval [CI] of 77-98) was obtained. There were 11 complete responses and 17 partial responses. Toxicity was mild, with a low incidence of undesirable effects (7 cycles, 2.9% were delayed from 3 to 6 days because of neutropenia). After a median follow-up time of 490 days (range, 131-966 days), the median time to progression was 490 days (95% CI 314-575), and the median survival was 604 days (95% CI 513-785). This epirubicin plus docetaxel regimen is an efficient treatment for patients with advanced breast cancer. The lenograstim support allows the administration of such a chemotherapy regimen with a modest incidence of side effects. A larger number of patients need to be evaluated.