First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study.

BACKGROUND: This randomized, phase III study compared the efficacy and safety of first-line gemcitabine versus epirubicin in the treatment of postmenopausal women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged > or = 60 years (median 68 years) with clinically measurable MBC received either gemcitabine 1200 mg/m(2) or epirubicin 35 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: Of 410 patients entered, 397 (198 gemcitabine and 199 epirubicin) were randomized and qualified for the time to progressive disease (TTP) and survival analyses. Total cycles administered in 185 gemcitabine and 192 epirubicin patients, respectively, were 699 (mean 3.5, range 0-12) and 917 (mean 4.6, range 0-10). Epirubicin demonstrated statistically significant superiority in TTP (6.1 and 3.4 months, P=0.0001), overall survival (19.1 and 11.8 months, P=0.0004), and independently assessed response rate (40.3% and 16.4% in 186 and 183 evaluable patients, P <0.001). For gemcitabine (n=190) and epirubicin (n=192), respectively, common WHO grade 3/4 toxicities were neutropenia (25.3% and 17.9%) and leukopenia (14.3% and 19.3%). Of the 28 on-study deaths (17 gemcitabine, 11 epirubicin), three were considered possibly or probably related to treatment (gemcitabine). CONCLUSIONS: Postmenopausal women > or =60 years of age with MBC tolerate chemotherapy well. In this study, epirubicin was superior to gemcitabine in the treatment of MBC in women age > or =60, confirming that anthracyclines remain important drugs for first-line treatment of MBC.     

Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer

Background: The mitoxantrone combination CNF and the epirubicin combination CEF have shown similar activity and less toxicity than the standard CAF combination in metastatic breast cancer (MBC). A prospective randomised study was started to compare safety and activity between CEF and CNF administered using a classical chemotherapeutic schedule in MBC.Patients and methods: From December 1987 to June 1993, 151 patients were randomised to receive cyclophosphamide (C) 100mgm^–2 p.o. days 1–14, fluorouracil (F) 500mgm^–2 i.v. days 1 and 8, and epirubicin (E) 30mgm^–2 i.v. days 1 and 8, or mitoxantrone (N) 6 mgm^–2 i.v. days 1 and 8, every 4 weeks. Seventythree patients were eligible for CEF and 72 for CNF.Results: Objective responses were observed in 61.6 of the CEF group and 44.4 in CNF group (p=0.004). The median duration of response was 64 weeks in CEF and 50 weeks in CNF group (p=0.02) and median time to progression was 51 and 33 weeks, respectively (p=0.0004). At the time of analysis, all except six patients (one in CNF and five in CEF) had died and the median survival time in the CEF group was longer than in CNF (74.4 weeks vs 51.4 weeks; log-rank ² test p=0.015). CNF produced more hematologic toxicity than CEF (WHO scale; grades 2–4): leucopenia 84% vs 68% (p=0.03) and trombocytopenia 17% vs 4.5% (p=0.01); CEF caused more grade 2 and 3 alopecia: 93% vs 70% (p=0.00 1).Conclusion: The combination CEF using this schedule and dosage in metastatic breast cancer is more effective with less toxicity than CNF, except for alopecia, and was associated with longer survival.     

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m² combined with either epirubicin 40 mg/m² or mitoxantrone 10 mg/m². All drugs were given by intravenous push, treatment cycles were repeated at 3–4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.     

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.     

两种方案治疗转移性乳腺癌的临床评价与药物经济学分析

  目的  从药物经济学角度对紫杉醇联合卡铂或表柔比星两种转移性乳腺癌化疗方案进行分析,为临床用药提供参考。  方法  采用成本-效果分析法对TP、TE(T:紫杉醇,P:卡铂,E:表柔比星)两种方案进行临床病例的回顾性分析比较。  结果  中位随访期为23.5(9~42)个月,TP、TE两组方案的有效率分别为78.33%和80.00%;1年、2年无进展生存率分别为43.6%和38.9%、10.8%和17.4%;1年、2年总生存率分别为80.3%和78.3%、53.2%和47.9%,两组之间无统计学差异(P>0.05)。成本-效果分析结果表明,两方案治疗成本分别为10 303.8元和13 853.3元,成本/效果比分别为131.54和173.17(P < 0.01)。化疗不良反应方面,TP组脱发发生率明显低于TE组(P < 0.01)。  结论  两方案近期与远期疗效相当,TP方案成本-效果高于TE方案,可作为晚期乳腺癌的优选方案之一。      

Vinorelbine alternating oral and intravenous plus epirubicin in first-line therapy of metastatic breast cancer: results of a multicentre phase II study

The combination of intravenous (i.v.) vinorelbine and epirubicin is highly active in the treatment of metastatic breast cancer (MBC). In an effort to improve patient convenience, we investigated a regimen alternating i.v. and oral vinorelbine in combination with epirubicin as first-line chemotherapy of patients with MBC. In all, 49 patients with MBC received, as first-line treatment, a combination regimen consisting of i.v. vinorelbine 25 mg m(-2) plus epirubicin 90 mg m(-2) given on day 1, and oral vinorelbine 60 mg m(-2) on day 8 (or day 15 if neutrophils <1500 mm(-3)) every 3 weeks, in an open-label, multicentre phase II study. Treatment was to be repeated for a maximum of six cycles. The study population had a median age of 55 years, half of the patients had received prior adjuvant chemotherapy and 86% presented a visceral involvement. In all, 25 responses were documented and validated by an independent panel review, yielding response rates of 51% (95% CI: 36-66) in the 49 enrolled patients and 54.5% (95% CI: 39-70) in the 44 evaluable patients. Median durations of progression-free survival and survival were 8 and 20 months, respectively. Neutropenia was the main dose-limiting toxicity, but complications were uncommon, four patients having experienced febrile neutropenia and six having developed neutropenic infection. Other frequently reported adverse events included stomatitis, nausea and vomiting, which were rarely severe. No toxic death was reported. Among patients who received six cycles, global score of quality of life remained stable. This regimen alternating oral and i.v. vinorelbine in combination with epirubicin is effective and safe. Oral vinorelbine on day 8 offers greater convenience to the patient, and decreases the need for i.v. injection and reduces time spent in hospital. Therefore, oral vinorelbine is a convenient alternative to the i.v. form in combination regimens commonly used to treat MBC.     

Activity of first-line epirubicin and paclitaxel in metastatic breast cancer is independent of type of adjuvant therapy

To evaluate the impact of prior adjuvant chemotherapy on response rate (RR), progression-free (PFS) and overall survival (OS) of metastatic breast cancer patients treated with epirubicin/paclitaxel (ET) regimens. In all, 291 patients enrolled in five studies in metastatic breast cancer were analysed: 101 (35%) were chemonaive, 109 (37%) had received adjuvant CMF and 81 (28%) adjuvant anthracyclines. Response rate to ET was 66%. Response rate was 63% for cyclophosphamide plus methotrexate plus 5-fluorouracil (CMF), 67% for prior anthracyclines and 68% in chemonaive patients (P=0.5). By multivariate analysis, adjusted odds ratio for response was 0.81 (95% CI: 0.37-1.79) for CMF and 0.92 (95% CI 0.43-2.01) for anthracyclines (P=0.86). The CR rates were 14% for both CMF and anthracyclines and 22% for chemonaive patients (P=0.2). By multivariate analysis, the relative odds of CR for CMF or anthracyclines were 0.40 and 0.39 as compared to chemonaive patients (P=0.036). The median PFS was 11.0 months for prior CMF, 10.2 months for anthracyclines and 12.5 months in chemonaive patients (P=0.33). In multivariate Cox's model, a nonsignificant increase in the risk of progression was seen in patients treated with adjuvant CMF or anthracyclines. The median OS was 23.8 months for CMF, 20.2 months for anthracyclines and 27.5 months in chemonaive patients (P=0.61). The same, nonsignificant, association was seen in multivariate analysis. The ET regimens provide satisfactory results in metastatic breast cancer, regardless of previous adjuvant chemotherapy.     

Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2).

BACKGROUND: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. PATIENTS AND METHODS: Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. RESULTS: A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. CONCLUSIONS: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.     

Epirubicin/vinorelbine as first line therapy in metastatic breast cancer

This study was aimed at investigating the toxicity and activity of the combination epirubicin and vinorelbine in chemotherapy-naive patients with metastatic breast cancer. Fifty-one patients with measurable or evaluable metastatic breast cancer entered the study. The regimen consisted of epirubicin 90 mg/m² as a slow i.v. infusion on day 1, followed by vinorelbine 25 mg/m² by 30-minute intravenous infusion on days 1 and 8; the courses were repeated every 21 days for a maximum of 8 cycles. All the patients were assessable for toxicity and 47 were evaluable for response according to the World Health Organization (WHO) criteria.Objective responses were observed in 33 out of 47 evaluable patients (70.2%; 95% C.I. 55.1%–82.6%) with 4 complete (8.5%) and 29 partial responses (61.7%); 11 patients had stable disease (23.4%) and 3 patients progressed while on treatment. The median time to progression was 10 months (range 1 – 21) and the median overall survival was 23 months (range 2 – 32+). Neutropenia was the most frequent toxicity: a grade 4 neutropenia (WHO) was reported in 70% of 252 courses with a median duration of 3 days (range 1–6). Seventeen episodes of febrile neutropenia were observed but only 1 patient required hospital admission. Other hematologic toxicities were negligible. One patient experienced a paralytic ileus requiring hospitalization; no peripheral neuropathy such as muscle weakness or paresthesia was observed. No treatment-related cardiotoxicity was reported. The encouraging response rate achieved with epirubicin/vinorelbine, the easily manageable toxicities of the combination, and its feasibility in an outpatient setting make this combination worthy of further comparative trials with standard regimens.     

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.     

Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer: a randomised phase II trial

The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 100 x mg x m(-2) docetaxel and FEC 75 cyclophosphamide 500 mg x m(-2), fluorouracil 500 x mg x m(-2) and epirubicin 75 mg x m(-2), in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3-4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (< or =9%) developed grade 3-4 non-haematological toxicities. Relative dose intensity was 97-99% for all regimens. All treatment regimens were active and well tolerated.     

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.     

Cost-effectiveness analysis of breast cancer adjuvant treatment: FEC 50 versus FEC 100 (FASG05 study).

BACKGROUND: The aim of the study was to assess the incremental cost-effectiveness ratio (ICER) of the FEC 100 compared with the FEC 50 in the FASG05 trial. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a multi-state Markov process model. Relevant clinical data introduced into the model were obtained from 10-year follow-up of the clinical trial FASG05. Survival curves for each health state were assessed by survival parametric model. The model allowed assessments from the start of adjuvant chemotherapy until death. The costs of adjuvant treatment and follow-up were estimated. The costs of recurrence were evaluated from the medical records of 146 patients. A prospective survey was performed on a cohort of 87 patients to quantify the resources external to the hospital (including cost of transportation). The inpatient costs were evaluated using the French diagnosis-related groups. The ambulatory costs were assessed using the French nomenclature. Costs were expressed in 2002 Euro (), according to the French societal perspective. The ICER assessed the cost of one additional life year saved. A discount rate of 5% per year was used for cost, and alternatively 0%, 3% and 5% for effectiveness. We validated the results with a probabilistic sensitivity analysis incorporating parametric and non-parametric bootstraps, and with the acceptability curves. RESULTS: The mean total discounting cost of adjuvant treatments was 11 465 for FEC 50 and 13 815 for FEC 100; the mean total discounting cost of recurrences was 14 636 and 13 503, respectively. According to the discount rate of effectiveness, the life expectancy was 16.5, 11.4 and 9.3 years for FEC 50 and 18.4, 12.5 and 10.2 years for FEC 100. The ICER (cost per life year saved) were 642, 1084 and 1460, respectively. The probability according to which FEC 50 is strictly dominated by FEC 100 was 0.15. CONCLUSION: The clinical benefit of FEC 100 generates a negligible cost increase when compared with FEC 50.     

Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. METHODS: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.     

Clinical comparison on the safety and efficacy of fluorouracil/pirarubicin/cyclophosphamide (FPC) with fluorouracil/ epirubicin/cyclophosphamide (FEC) as postoperative adjuvant chemotherapy in breast cancer

Objective: To compare the safety and efficacy of a combination of 5-Fu, pirarubicin and CTX (FPC) withFEC as a postoperative adjuvant chemotherapy for breast cancer. Methods: A total of 655 breast cancer patientswere treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1995-2005, 292 were treatedwith FPC (5-Fu 500mg/m2 iv gtt on day 1, pirarubicin 40mg/m2 iv on day 1, CTX 500mg/m2 iv on day 1 and acycle repeated every 21-28 days for totally 4-6 cycles); 363 with FEC (5-Fu 500mg/m2 iv gtt on day 1, epirubicin50mg/m2 iv on day 1 and day 2, CTX 500mg/m2 iv on day 1 and a cycle repeated every 21-28 days for totally4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy. Results: Main side effects in both FPC andFEC groups were leukopenia and gastrointestinal toxicity, with a 5 year survival rate 88.7% in FPC and 85.7%in FEC group. Conclusions: FPC regimen is safe with superior long-term survival rate when compared withFEC, thus could be recommended as a postoperative chemotherapy regimen for Chinese patients with breastcancer.     

A retrospective clinical study of safety and efficacy of vinorelbine/epirubicin/fluorouracil （NEF） regimen as a postoperative chemotherapy for breast cancer

Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer patients were treated with the NEF regimen： vinorelbine 25 mg/m^2 iv on days 1 and 8; epirubicin 60 mg/m2 iv gtt on day 1; 5-Fu 500 mg/m2 iv gtt on day 1. Chemotherapy was repeated every 21-28 days for a total of 6 cycles. Results： The major side effects were neutrope- nia and gastrointestinal syndrome, with a 5-year survival rate of 85.4%, Conclusion： NEF regimen is safe and guarantees a high survival rate which could be recommended as a adjuvant chemotherapy regimen for breast cancer,     

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.     

Adjuvant epirubicin followed by cyclophosphamide,methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials

Background:

The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses.

Methods:

National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles.

Results:

In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65–0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65–0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours.

Conclusion:

Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.