Optimal use of taxanes in metastatic breast cancer

The role of taxanes in the treatment of breast cancer is becoming increasingly important. In clinical practice, the taxanes are now standard therapy in both early-stage and metastatic breast cancer. Since the 1990s, multiple randomized clinical trials have been evaluating the efficacy of taxanes in the treatment of metastatic breast cancer. These trials have included treatment with taxanes alone or in combination with other chemotherapeutic agents. Pre-existing published guidelines for the use of taxanes in the management of metastatic breast cancer are available. The mandate of the Alberta Cancer Board Provincial Breast Tumour Group Guideline Panel was to consider and adapt the recommendations of the existing guidelines and to develop de novo guidelines to account for current evidence. For this task, the panel used the adapte process, which is a systematic process of guideline adaptation developed by the adapte Collaboration.The recommendations formulated by the panel included the identification of taxane regimens that could be offered in anthracycline-naïve patients, anthracycline-pretreated or -resistant patients, and patients overexpressing the human epidermal growth factor receptor 2. Potential toxicities and benefits in terms of time to progression, progression-free survival, overall survival, and quality of life were also considered.     

Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile.Patients and methods: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with 2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography.Results: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) <0.1 × 109/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2 and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 × 109/l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotoxicity. Antitumour activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%–75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2–30+), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months.Conclusions: The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimens.     

Emerging therapeutic options for breast cancer chemotherapy during pregnancy.

BACKGROUND: Breast cancer is the commonest solid tumor observed during pregnancy. Anthracycline-based chemotherapy is feasible during the 2nd and 3rd trimesters of pregnancy, but few data are available on recent and highly active drugs taxanes, vinorelbine and anti-HER-2 agents in this setting. PATIENTS AND METHODS: We carried out a comprehensive review of reports documenting the use of taxanes, vinorelbine, trastuzumab and lapatinib during pregnancy in the English literature, in order to evaluate their safety profile in pregnant patients. RESULTS: Twenty-four pregnancies are described, in which no grade 3-4 maternal toxicity nor malformation in the offspring was reported. Whereas only one report studied the pharmacokinetics of paclitaxel (Taxol) during pregnancy, several preclinical reports indicate that the placental P-glycoprotein could prevent the transplacental transfer of taxanes and vinorelbine. The use of trastuzumab was associated with the occurrence of anhydramnios in three of six cases. CONCLUSION: The administration of recent drugs taxanes and vinorelbine seems feasible during the 2nd and 3rd trimesters of pregnancy, with a favorable toxicity profile. In contrast, anti-HER-2 agents may obscure the normal development of the fetal kidney, and should be avoided during pregnancy.     

Immune dysfunction and micrometastases in women with breast cancer

Cytokines produced by T lymphocytes are critical to the efficacy of a given immune response and dysregulation of immune responses may play a role in cancer progression. We assessed the intracellular cytokine profiles of T cells in the peripheral blood of women with breast cancer and explored the relationship of these responses with the presence of cancer in lymph nodes and bone marrow. Peripheral blood lymphocytes from 84 patients and 26 healthy volunteers were analyzed by 4-color flow cytometry for surface markers and for intracellular cytokines. Bone marrow samples from some of these patients were also collected and analyzed for the presence of epithelial cells (micrometastases) by flow cytometry. The percentages of both CD4⁺ and CD8⁺ cells producing type1 (IL-2, IFN- or TNF-) and type 2 (IL-4) were significantly lower in patients with breast cancer compared to healthy controls. These results indicate a general immune dysfunction in these patients as opposed to a shift in the balance of type1 and type2 cells. These dysregulated T cell responses did not correlate with age, stage of disease, or nodal status. However, we did observe a correlation between number of micrometastases in the bone marrow and T cell responsiveness.     

Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I-II study.

Background:The combination of anthracyclines and taxanes iscurrently considered the first choice chemotherapy in advanced breast cancer(ABC) and considerable emphasis has been placed on programs exploring thesafest and most efficient way to integrate these classes of drugs in both themetastatic and, more recently, the adjuvant setting.We report here the overall results of the combination of epidoxorubicin (E)90 mg/m² and docetaxel (D) 75 mg/m² as first-linechemotherapy in ABC. Patients and methods:A total of 70 patients were entered in theinitial dose-finding study (20 patients) and in the subsequent extended phaseII trial (50 patients). Overall 54% of patients had dominant visceraldisease and 57% had at least two metastatic sites. Adjuvantanthracyclines were allowed in the phase II part of the study based on thelack of cardiac toxicity observed in the phase I study at a median cumulativeE dose of 480 mg/m². A maximum of eight cycles of the combinationwas allowed, and cardiac function was monitored at baseline and after everysecond course by echocardiography. Results:Overall, the median number of cycles administered withthe combination was 4 (range 3–8). Neutropenia was confirmed to be themain haematological toxicity, with granulocyte colony-stimulating factor(G-CSF) support required in 44% of the cycles. Febrile neutropeniaoccurred in 12% of cycles of the combination but 52% of theepisodes could be managed on an outpatient basis with oral antibiotics.Overall, the median cumulative dose of E, including prior adjuvantanthracyclines, was 495 mg/m² (range 270–1020mg/m²). One patient who received adjuvant E together withradiotherapy to the left chest wall developed fully reversible clinical signsof cardiotoxicity and a significant decrease of LVEF to 35% after acumulative E dose of 870 mg/m², with four additional patients(6%) developing asymptomatic and transient decline of resting LVEF. Theoverall response rate (ORR) in 68 evaluable patients was 66%(95% confidence interval (95% CI): 54%–73%).A comparable antitumour activity of 71% was reported in the group ofpatients with a prior adjuvant chemotherapy with anthracyclines. After anoverall median follow-up time of 22 months (range 4–39+), the mediantime to progression (TTP) was 4.5 months and the median duration of responsewas 8 months (range 3–16). No pharmacokinetic (Pk) interaction could bedemonstrated between E and D when given simultaneously and sequentially witha one-hour interval. Conclusions:The combination of E and D in a multi-institutionalsetting is an active and safe regimen in poor- prognosis patients with ABC.New combinations and schedules are worth considering in an attempt to furtherimprove disease response and long-term control of the disease.     

多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.     

Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer

Aim:to evaluate the activity and acute toxicity of thecombination of weekly paclitaxel as first-line chemotherapy andtrastuzumab, in patients with HER-2/neu overexpressing advanced breastcancer (ABC). Background:Weekly paclitaxel has beenshown to be a well tolerated treatment with considerable activity inpatients with ABC. Clinical trials with transtuzumab, a humanizedanti-p185 HER-2/neu monoclonal antibody have demonstrated that thisagent produces objective responses in patients with ABC. Patients and methods:From December 1998 to April 2000, 34patients with HER-2/neu overexpressing ABC were treated with weeklypaclitaxel; given by one-hour infusion at a dose of 90 mg/m²immediately followed by trastuzumab, 4 mg/kg as a loading dose and2 mg/kg i.v. given over 30 min, thereafter weekly for at least 12 weeks.Expression of HER-2/neu was determined by immunohistochemical analysison fixed, paraffin-embedded tissues. Eligible patients were required tohave 25% stained tumor cells. Results:Thirty-three patients completed at least 12 weeks of combinedtreatment. After completion of the 12th week of treatment, four patients(12%) achieved complete and 17 (50%) partial response.Median duration of response was 11.6 months. More frequent side effectsincluded anemia (56%), neutropenia (27%), peripheralneuropathy (78%), diarrhea (30%), alopecia (70%),arthralgias/myalgias (62%), fatigue (59%) andhypersensitivity reactions (62%). Median time to progression wasnine months while median survival had not been reached Conclusions:The combination of weekly paclitaxel andtrastuzumab is a safe and active regimen for patients with HER-2/neuoverexpressing ABC. Randomized phase III studies with this combinationare warranted.     

多西紫杉醇联合卡培他滨治疗蒽环类耐药的晚期乳腺癌

目的：观察多西紫杉醇联合卡培他滨方案治疗对蒽环类耐药的晚期乳腺癌的疗效及毒副反应。方法：24例患者给予多西紫杉醇75mg/m^2静滴d1,卡培他滨1650mg/m^2.d,口服,d1-d14。21天为1周期,至少用2个周期,中位化疗周期数3个（2-4周期）。结果：总有效率41.7%,疾病控制率为83.3%,中位生存期16.5个月,主要毒副作用为骨髓抑制和脱发。结论：多西紫杉醇联合卡培他滨治疗对蒽环类耐药的晚期乳腺癌疗效好,毒副作用轻,是治疗对蒽环类耐药晚期乳腺癌较好的方案。     

The clinical observation of neoadjuvant chemotherapy in locally advanced breast cancer with DX regimen

The recent clinical curative effect and adverse events of docetaxel and capecitabine （DX） of neo- adjuvant chemotherapy in patients with locally advanced breast cancer was discussed. Methods： The data of 72 cases of neoadjuvant chemotherapy （DX） in locally advanced breast cancer after 4 cycles were retrospectively analyzed. Docetaxel 75 mg/m^2 by infusion 1 h on dl, capecitabine 2000 mg/m^2 by oral for twice daily on d1-14, 21 days was a cycle. Results： All 72 patients were assessed for efficacy and adverse events. The total effective rate was 80.5% （58/72）, including pathological complete response （pCR） was 7 （9.7%）, clinical complete remission （cCR） was 15（20.8%）, clinical partial response （PR） was 43 （59.7%）, stable disease （SD） was 8 （11.1%） and progressive disease （PD） was 6 （8.3%）. The main adverse events were gastrointestinal reactions and bone marrow suppression. The 3 to 4 degrees of adverse reactions including granulocytopenia in 7 patients （20.6%）, hand-foot syndrome in 6 patients （15.2%）. Conclusion： The DX regimen provide a favorable efficacy and safety profile in patients with locally advanced breast cancer for neoadjuvant chemotherapy.     

Primary docetaxel chemotherapy in patients with breast cancer: impact on response and survival

Primary chemotherapy achieves high clinical response rates and facilitates breast conservation in many patients with large and locally advanced breast cancer. It may also serve to indicate responsiveness to chemotherapeutic agents. A pathological complete response to primary chemotherapy is a primary predictor and surrogate marker of long-term outcome, but occurs in only approximately 15% of patients. Docetaxel is of particular interest in this setting. Primary docetaxel chemotherapy has single-agent activity in both dose-dense and traditional schedules, with acceptable tolerability. Furthermore, concomitant docetaxel–anthracycline schedules have shown promise in Phase II trials, achieving clinical overall response rates (ORRs) of 77–96%, pathological complete responses of up to 24%, and breast conservation in up to 89% of patients.Two Phase III studies have shown that pathological complete response is significantly improved with the addition of docetaxel to anthracycline-based therapy versus the latter alone: the Aberdeen study achieved a rate of 34% versus 16%, respectively (p = 0.04), and the NSABP-B27 study a rate of 26% versus 14%, respectively (p < 0.001). The Aberdeen study has suggested that the addition of docetaxel may yield a survival benefit at 5 years (p = 0.04). The Phase II GEPAR-DUO study hints at a benefit for sequential over concomitant docetaxel-based therapy, with improvements in both clinical response (ORR 87% versus 77%, respectively) and pathological complete response (23% versus 12%, respectively). Non-anthracycline docetaxel-based primary regimens have shown early promise. As we continue to define the optimal regimen, a growing body of evidence supports the use of docetaxel in primary chemotherapeutic regimens for breast cancer.     

Preoperative taxane-based chemotherapy in a standardized protocol for locally advanced breast cancer

Aims: To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) in predicting the extent of residual disease. Methods: Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m² (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate. Results: Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol‐specified time and 12 (23%) patients had breast conservation surgery. At a median follow‐up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease‐free survival. Conclusion: This regimen of TAC is effective and well‐tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.     

Efficacy of weekly paclitaxel in patients with docetaxel-resistant metastatic breast cancer

Summary Background. Partial cross-resistance to paclitaxel and docetaxel has been demonstrated in pre-clinical studies.Patients and methods. We retrospectively evaluated the efficacy of weekly paclitaxel 80 mg/m² in 82 patients with docetaxel-resisitant metastatic breast cancer. Docetaxel resistance was classified into primary resistance, defined as progressive disease while receiving docetaxel, and secondary resistance, defined as progression after achievement of a documented clinical response to docetaxel. Secondary resistance was subclassified according to the interval between the final infusion of docetaxel and the start of weekly paclitaxel into: (1) short interval, 120 days, and (2) long interval, >120 days. Results. The response rate of the 82 patients was 19.5% (95% confidence interval, 10.8–27.9%). The response rate according to the docetaxel resistance category was: primary resistance (n=24), 8.3%; secondary resistance (n=58), 24.1% (short interval [n=39], 17.9%, and long interval, [n=19], 36.8%). The differences in response rates among the three categories were statistically significant (p=0.0247, Cochran–Mantel–Haenszel test). The interval between from the final docetaxel infusion and disease progression were predictors for response of weekly paclitaxel. Conclusion. Weekly paclitaxel is modestly effective and safe in docetaxel-resistant metastatic breast cancer patients. However, weekly paclitaxel should not be recommended for primary resistance patients with docetaxel.     

Combination chemotherapy with docetaxel plus vinorelbine in metastatic breast cancer patients with prior exposure to anthracyclines

Purpose:To evaluate the anti-tumor activity and tolerance ofdocetaxel plus vinorelbine in metastatic breast cancer (MBC) patientspreviously treated with anthracyclines. Patients and methods:Fifty patients with MBC were treated withdocetaxel 75 mg/m² (subsequently reduced to 60 mg/m²)plus vinorelbine 30 mg/m² (subsequently reduced to 24mg/m²), both on day 1, every 3 weeks, for a maximum of six cycles.All patients had previously received anthracyclines as adjuvant treatment(<12 months disease-free interval) or first-line therapy for MBC.Thirty-seven patients had received at least one prior regimen for MBC.Twenty-five patients had prior high-dose chemotherapy with stem-cell rescue.Thirty patients had multiple metastatic sites. Liver and lung disease were thepredominant metastatic site in 31 patients. Results:Forty-nine patients were assessable for response.Nineteen patients achieved a partial response and four a complete response(overall response rate, 46%; 95% confidence interval (95%CI): 32%–60%). Fourteen patients (28%) had stabledisease on treatment. Median Kaplan–Meier estimated progression-free andduration of response times are 21 and 29 weeks. Median survival time is 47weeks. Hematological dose-limiting toxicity, prompted a 20% dosereduction for both drugs after the first thirteen patients were treated.Neutropenia grade 3 occurred in nineteen (34%) patients,neutropenic fever in 15 (7%) courses, and mucositis grade 3 in 6(3%) courses. Conclusions:The combination of docetaxel plus vinorelbine on day1 every 3 weeks is feasible and active in MBC patients with prioranthracycline exposure. This regimen is safe, well-tolerated and convenientfor the patients.     

长春瑞滨联合紫杉醇治疗晚期乳腺癌

背景与目的：长春瑞滨（商品名诺维本、NVB）其作用阻滞微管蛋白聚合和诱导微管的解聚，而紫杉醇相反，它促进微管蛋白的聚合，阻微管正常的生理性解聚：本文观察长春瑞滨联合紫杉醇治疗晚期乳腺癌的临床疗效疗效和毒副反应方法：42例经病理学和细胞学证实的晚期乳腺癌患者应用长春瑞滨25mg/m^2，静脉滴注，第1、8d；紫杉醇175mg/m^2，静脉滴注3h，第1天；在紫杉醇静脉滴注之前12h、6h，分别口服地塞米松20mg，给药前30min肌注非那根25mg和西米替丁300mg静脉滴注。21d为一个周期，完成2～4个周期后评价疗效：结果：全组总缓解率（RR）66．7％，填中完全缓解率（CR）16．7％，初次化疗患者RR72．2％，CR27．7％；再次化疔患者RR62．1％，CR8．3％，2，4年生存率分别为40．5％（17／42）和21．4％（9／42）；中位缓解期为8个月（5～17个月），中化生存期为18个月；主要毒副反应为骨髓抑制，脱发和周围静脉炎：结论：长春瑞滨联合紫杉醇方案治疗晚期乳腺癌有很好的疗效，且毒副反心患者可耐受。     

Metastatic breast cancer in pregnancy: first case of chemotherapy with docetaxel

The focus of this paper is a case study of a woman in the first trimester of pregnancy who presented with metastatic breast cancer. The bony spread of the metastases was rapid and it was necessary to treat the patient as soon as possible after the period of organogenesis (days 18–60 of human gestation). This stage is the phase of greatest sensitivity of teratogens and the malformations are observed most often. Yet, the choice of third-line chemotherapy was difficult because of anthracycline-resistant metastatic breast cancer. The world literature reported cytotoxic combinated regimens as the standard of care for the management of the metastases. The development of new antitumoral strategies with less toxicity and their encouraging results led us to the approval of docetaxel for the treatment of the patient even though it had never been tested in pregnancy. Docetaxel is a potent inhibitor of microtubule depolymerization and has a unique ability to alter certain classes of microtubules. The monochemotherapy was administered once every 3 weeks for a total of three cycles until 30 weeks of gestation. During the 32nd week of pregnancy the patient delivered a female infant whose birthweight and Apgar score were normal. The infant did not have any anomalies. The woman finished her treatment in puerperium and she received three cycles of docetaxel. The patient has been receiving vinorelbine (one cycle every 2 weeks) for 2 years; her last follow-up was good and showed that the progression of the metastases had stopped. The daughter's psychophysical development was normal.     

Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: A multicenter phase II trial

Purpose: The activity of the docetaxel–gemcitabine combination in women with disease progression after initial chemotherapy for metastatic breast cancer (MBC) was investigated in a multicenter phase II study.Patients and methods: Fifty-two patients with metastatic breast cancer who had disease relapse or progression after completion of an anthracycline-based front-line regimen were treated with gemcitabine 900 mg/m2 on day 1 and day 8 and docetaxel 100 mg/m2 on day 8. G-CSF 150 µcg/m2/d s.c. was given from day 9 to day 16 and the treatment was repeated every three weeks. The patients' median age was 57 years and the performance status (WHO) was 0 for 26, 1 for 20 and 2 for 6 patients. The treatment was second-line for 27 (52%) and third-line for 25 (48%) patients. All patients were evaluable for response and toxicity.Results: Complete response occurred in seven (14%) patients and partial response in 21 (40%) for an overall response rate of 54% (95% confidence interval (95% CI): 40%–67%). Fifteen (29%) patients had stable disease and nine (17%) progressive disease. Of 25 patients previously treated with taxanes, 11 (44%) responded (1 CR, 10 PR). Interestingly, in four patients with disease progression while receiving docetaxel or paclitaxel monotherapy, the docetaxel + gemcitabine combination achieved partial responses. Responses were observed at all metastatic sites (local disease 62%, lymph nodes 58%, skin 44%, lung 47% and liver 36%) with a median duration of response of 3.6 months (range 1–16) and a median time to disease progression of eight months (range 2–18.5). Grade 3 neutropenia developed in 10 (19%) and grade 4 in five (10%) patients. Neutropenia was associated with infection in four patients without toxic deaths. Grade 3 thrombocytopenia developed in nine (17%) patients and grade 4 in two (4%). Non-hematologic toxicity was usually mild.Conclusion: The docetaxel–gemcitabine combination is an active and well tolerated salvage treatment in patients with MBC. Previous treatment with taxanes does not preclude a good clinical response to this regimen.     

希罗达联合艾素治疗晚期乳腺癌的临床观察

目的:研究希罗达联合艾素方案治疗晚期乳腺癌的近期疗效及毒副反应。方法:51例晚期乳腺癌患者,均经病理组织学证实。治疗方案希罗达1250mg/m2日两次口服d1～14,艾素35mg/m2静脉滴注d1,8,21天1周期,至少2周期评价疗效。结果:51例中完全缓解(CR)3例,部分缓解(PR)22例,无变化(NC)16例,进展(PD)10例,总有效率(RR)49.01%,1年生存率78.26%。毒副反应主要为骨髓抑制,消化道反应,可耐受。结论:希罗达联合艾素治疗晚期乳腺癌疗效肯定,毒副反应小,是治疗晚期乳腺癌较好方案,值得临床推广。     

晚期乳腺癌联合化疗的临床观察

目的 观察紫杉醇联合表阿霉素（TE方案）及诺维本联合表阿霉素（NE方案）治疗晚期乳腺癌的临床疗效和不良反应。方法 对120例晚期乳腺癌患者随机分为TE组58例和NE组62例，分别进行治疗观察。结果 TE组总有效率（65.5 %）和复治有效率（61.8 %）高于NE组（38.7 %和27.8 %），中位疾病进展时间长于NE组（P＜0.05）；两组初治有效率和中位生存期无显著差异（P＞0.05）；不良反应以骨髓抑制、胃肠反应和脱发为主，两组无显著差异性；NE组静脉炎、TE组关节肌肉酸痛的发生率相对高，但均可耐受。结论 紫杉醇联合表阿霉素和诺维本联合表阿霉素对晚期乳腺癌均有较好疗效，但TE组对复治患者疗效更好，可作为复治的晚期乳腺癌患者首选化疗方案。     

Phase I-II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

Given the established individual activity of docetaxel and ifosfamide in anthracycline pretreated advanced breast cancer, the present phase I-II study aimed to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and activity of the docetaxel-ifosfamide combination in this setting. Cohorts of three to six patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel 70-100 mg x m(-2) over 1 h on day 1 followed by ifosfamide 5-6 g x m(-2) divided over days 1 and 2 (2.5-3.0 g x m(-2) day(-1) over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. In total, 56 patients with a median age of 54.5 (range, 32-72) years and performance status (WHO) of 1 (range, 0-2) were treated at five DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 35 were treated at DL4 (total of 41 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 53 for response. Dose-limiting toxicity (with the addition of G-CSF after DL2) was reached at DL5 with two out of three initial patients developing febrile neutropenia (FN). Clinical response rates, on an intention-to-treat basis, in phase II were: 53.6% (95% CI, 38.3-68.9%); three complete remissions, 19 partial remissions, seven stable disease, and 12 progressive disease. The median response duration was 7 months (3-24 months), median time to progression 6.5 month (0.1-26 month), and median overall survival 13 months (0.1-33 months). Grade 3/4 toxicities included time to progression neutropenia in 78% of patients-with 63% developing grade 4 neutropenia (相似文献   

Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: This study was conducted to assess the antitumour activity of docetaxel in combination with doxorubicin for neoadjuvant therapy of patients with breast cancer. PATIENTS AND METHODS: Forty-eight women were treated with intravenous doxorubicin 50 mg/m(2) over 15 min followed by a 1-h infusion of docetaxel 75 mg/m(2) every 3 weeks for six cycles. Dexamethasone or prednisolone premedication was allowed. Granulocyte colony-stimulating factor was not allowed as primary prophylaxis. The primary end point was the pathologically documented complete response rate (pathological response). RESULTS: The mean relative dose intensity calculated for four or more cycles was 0.99 for doxorubicin and 0.99 for docetaxel. Overall, the pathological response rate was 13%. There were 11 complete and 29 partial clinical responses for an overall response rate of 85% [95% confidence interval (CI) 75% to 95%] in the evaluable population (n = 47). Disease-free and overall survival rates were 85% (95% CI 71% to 94%) and 96% (95% CI 85% to 99%), respectively, after a median follow-up of 36.6 months. Grade 3/4 neutropenia was observed in 65% of patients and 17% reported grade 4 febrile neutropenia. CONCLUSIONS: Docetaxel and doxorubicin is an effective and well-tolerated combination in the neoadjuvant therapy of breast cancer. Future controlled trials are warranted to investigate the best schedules and to correlate response with biological factors.