共查询到20条相似文献,搜索用时 0 毫秒
1.
Ryan Q Ibrahim A Cohen MH Johnson J Ko CW Sridhara R Justice R Pazdur R 《The oncologist》2008,13(10):1114-1119
On March 13, 2007, the U.S. Food and Drug Administration approved lapatinib (Tykerb tablets; GlaxoSmithKline, Philadelphia), an oral, small molecule, dual tyrosine kinase inhibitor of ErbB-2 and ErbB-1, for use in combination with capecitabine for the treatment of patients with human epidermal growth factor receptor (HER)-2-overexpressing metastatic breast cancer who had received prior therapy including an anthracycline, a taxane, and trastuzumab. One multicenter, open-label, randomized trial was submitted. Eligible patients had stage IIIb or IV breast cancer, ErbB-2 overexpression (immunohistochemistry 3+ or 2+ with fluorescence in situ hybridization confirmation), measurable disease, a 0 or 1 Eastern Cooperative Oncology Group performance status score, a cardiac ejection fraction within the institutional normal range, and adequate laboratory function. Patients received either lapatinib (1,250 mg once daily on days 1-21) plus capecitabine (1,000 mg/m(2) every 12 hours on days 1-14) every 21 days or capecitabine alone (1,250 mg/m(2) every 12 hours on days 1-14) every 21 days. The primary endpoint was time to progression (TTP) determined by a blinded independent review panel. After TTP results of a prespecified interim analysis were made available, study enrollment was discontinued (399 patients enrolled). The median TTP was 27.1 versus 18.6 weeks (hazard ratio, 0.57; p = .00013) favoring the lapatinib plus capecitabine arm. Response rates were 23.7% (lapatinib plus capecitabine) versus 13.9% (capecitabine alone). Survival data were not mature. Although the toxicities observed in the lapatinib and capecitabine combination arm were generally similar to those in the capecitabine alone arm, a higher incidence of diarrhea and rash was noted with the combination. Grade 3 or 4 adverse reactions that occurred with a frequency of >5% in patients on the combination arm were diarrhea (13%) and palmar-plantar erythrodysesthesia (12%). There was a 2% incidence of reversible decreased left ventricular function in the combination arm. 相似文献
2.
目的 探讨立体定向放射治疗(Stereotactic radiotherapy,SRT)联合拉帕替尼治疗HER2阳性乳腺癌脑转移的疗效及预后。方法 回顾性分析91例HER2阳性乳腺癌脑转移患者接受拉帕替尼靶向治疗的同时接受全脑放疗或SRT的情况,其中42例患者接受SRT的同时进行拉帕替尼联合卡培他滨治疗(SRT组),另外49例患者采用全脑放疗同时进行拉帕替尼联合卡培他滨治疗(全脑放疗组)。评价其疗效和毒性,定期随访,并行多因素Cox回归分析其预后相关因素。结果 放疗结束后1月SRT组脑部病灶客观缓解率为92.86%(39/42),全脑放疗组客观缓解率为77.55%(38/49),SRT组优于全脑放疗组(χ2=4.070,P=0.044)。SRT组和全脑组12个月受照射肿瘤病灶无进展生存率分别为95.20%及83.10%, SRT组优于全脑放疗组(χ2=10.851,P=0.001)。 SRT组无颅内转移生存率与全脑放疗组无统计学差异(P>0.05)。SRT组和全脑放疗组1年生存率分别为85.70%和69.40%,2年生存率分别为66.70%和55.10%,两组中位生存期分别为31.56个月和25.00个月,SRT组优于全脑放疗组(P=0.002)。多因素Cox回归分析结果表明无颅外转移(HR=0.527,95% CI:0.290~0.957,P=0.035),颅内病灶≤3个(HR=2.457,95% CI:1.223~4.933,P=0.012),放疗方式SRT(HR=1.746,95% CI:1.055~2.888,P=0.030)是HER2阳性乳腺癌脑转移放疗预后的独立保护因素。结论 SRT联合拉帕替尼在局部控制率以及生存率上优于全脑放疗联合拉帕替尼。颅内病灶个数少、无颅外转移灶和放疗方式是HER2阳性乳腺癌脑转移治疗的良好预后因素。 相似文献
3.
目的 观察全脑放疗联合卡培他滨同步化疗治疗乳腺癌患者术后脑转移的疗效及不良反应。方法 50例乳腺癌术后脑转移患者信封法随机分为治疗组(全脑放疗联合卡培他滨同步化疗)和对照组(单纯全脑放疗)各25例。治疗组全脑照射为2 Gy/次,5次/周,总剂量40 Gy,放疗开始第1天给予卡培他滨850 mg/m2口服,2次/d,至放疗结束;对照组全脑照射同治疗组。放疗结束后3个月评价疗效。结果 治疗组和对照组1年生存率分别为60.0 %(15/25)、44.0 %(11/25)(χ2=1.28,P>0.05),2年生存率分别为28.0 %(7/25)、16.0 %(4/25)(χ2=1.05,P>0.05)。治疗过程中的不良反应可以接受。结论 全脑放疗联合卡培他滨同步化疗治疗乳腺癌患者术后脑转移是一种安全、有效的治疗方法,不良反应小。 相似文献
4.
Cyrus Chargari Youlia M. Kirova Véronique Diéras Pablo Castro Pena Francois Campana Paul H. Cottu JeanYves Pierga Alain Fourquet Institut Curie Breast Cancer Study Group 《Journal of neuro-oncology》2009,93(3):385-384
Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively
assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from
breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with
concurrent capecitabine. Median age was 44 years (range: 38–53). The median dose of capecitabine was 1,000 mg/m2 twice daily for 14 days (day1–14). Treatment cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per
fraction, 5 days per week). Median survival after starting WBRT plus capecitabine was 6.5 months (range 1–34 months). One
patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until
most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early
death. Most commonly reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1. Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1 mucositis (n = 1). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain
metastases from breast cancer and need to be further validated in the setting of a clinical trial.
An erratum to this article can be found at 相似文献
5.
Shigekawa T Takeuchi H Misumi M Matsuura K Sano H Fujiuchi N Okubo K Osaki A Aogi K Saeki T 《Breast cancer (Tokyo, Japan)》2009,16(1):88-92
We report a case of metastatic breast cancer with leptomeninges and multiple bone metastases that showed an excellent response
to the combination of trastuzumab and capecitabine; therapeutic effect was evaluated by MRI at follow-up. A 44-year-old woman
underwent modified radical mastectomy in February 1997. In April 2003, a tumor at the right basis cerebri and multiple bone
metastases were noted, and in October 2003, she underwent enucleation of the tumor. Histopathologically, the tumor was consistent
with a basal skull metastasis from breast cancer. In March 2004, the patient began to experience pain, weakness, and paresthesia
of both legs. She was diagnosed, with leptomeningeal metastasis (LM) from breast cancer using MRI. In December 2005, the combination
of trastuzumab and capecitabine administered as sixth-line treatment was very effective for LM. Although it is generally very
difficult to diagnose LM and assess the therapeutic effect with MRI, in this case, it was possible. To our knowledge, there
has been no report in the literature describing the combination of trastuzumab and capecitabine for LM from breast cancer.
Although the mechanism underlying the efficacy of this combination is still unknown, the treatment would be worth trying because
of its few side effects in extensively treated patients with LM from breast cancer. To confirm the antitumor efficacy of trastuzumab
and capecitabine, however, further investigations are required. 相似文献
6.
Hayakawa K Yamakawa M Mitsuhashi N Hasegawa M Kawashima M Sakurai H Murata O Nasu S Kurosaki H Niibe H 《Breast cancer (Tokyo, Japan)》1998,5(2):149-154
We have reviewed the medical records of 28 breast cancer patients with brain metastases who were treated with radiotherapy
at our clinic from 1980 through 1994 (4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered
as whole brain irradiation using lateral opposed 10 MV X-rays. Ten patients received an additional boost to a reduced field.
One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumors ranged from 32 Gy to
60 Gy (mean, 49 Gy) in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only
two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients (92%) with complete
response (CR) in 1 2 patients (46%) and partial response (PR) in 1 2 patients (46%). The survival rates from the initial treatment
were 39% at 5 years and 16% at 10 years (median survival time, 50 months), and those after treatment of brain metastases were
29% at one year and 18% at 2 years (median survival time, 6 months). Performance status tended to be associated with survival
(p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival (p=0.056). Two patients
suffered severe chronic complications. One patient developed severe dementia after whole brain irradiation with a total dose
of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy
with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain
metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except
for hepatic involvement. Radiation-related complications should therefore be avoided in these patients. 相似文献
7.
Gonzalo Jr Recondo Enrique Dìaz Canton Màximo de la Vega Martin Greco Gonzalo Sr Recondo Matias E Valsecchi 《World journal of clinical oncology》2014,5(3):440-454
During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available. 相似文献
8.
Janaina Brollo Giuseppe Curigliano Davide Disalvatore Bianca Fontana Marrone Carmen Criscitiello Vincenzo Bagnardi Maximiliano Cassilha Kneubil Luca Fumagalli Marzia Locatelli Silvia Manunta Aron Goldhirsch 《Cancer treatment reviews》2013
Trastuzumab, in combination with chemotherapy, is the gold standard in the adjuvant treatment of patients with HER2 positive breast cancer. Limited data are available on the role of adjuvant trastuzumab in the elderly population. We performed a systematic review of prospective randomized trials with available data on the use of adjuvant trastuzumab in patients older than 60 years, focusing on both the efficacy and the cardiac safety. Data extrapolated from two prospective trials were included for efficacy and cardiac safety. A significant 47% relative risk reduction was observed in elderly patients receiving trastuzumab compared to chemotherapy alone (pooled Hazard Ratio: 0.53; 95% CI, 0.36–0.77). The pooled proportion of cardiac events in elderly patients treated with trastuzumab was 5% (95% CI, 4–7%). The use of trastuzumab should be considered as a standard of care in the adjuvant therapy of elderly patients with HER-2 positive breast cancer. Acute and chronic medical conditions, nutritional status and level of daily activities should be considered. Uncertainty about cardiac safety in the elderly is a major concern. 相似文献
9.
Morohashi S Odagiri H Morohashi H Kimura Y Sasaki M 《Breast cancer (Tokyo, Japan)》2007,14(3):297-301
A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF beta, v0, ly1, pT2, pN1, M0, Stage II B ER (+/-), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered. Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future. 相似文献
10.
BackgroundPhosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin pathway is frequently activated in HER2-positive breast cancer and may play a major role in resistance to trastuzumab. Buparlisib is a pan-class-I PI3K inhibitor with potent and selective activity against wild-type and mutant PI3K p110 isoforms.Patients and methodsPIKHER2 phase IB study aimed primarily to determine a maximum tolerated dose (MTD) and propose a recommended phase II dose (RP2D) for buparlisib in combination with lapatinib in HER2-positive, trastuzumab-resistant, advanced breast cancer. Oral buparlisib (40, 60 or 80 mg) and lapatinib (750, 1000 or 1250 mg) were administered daily. A modified continuous reassessment method using an adaptive Bayesian model guided the dose escalation of both agents. Secondary end-points included antitumour activity and pharmacokinetic (PK) assessments.ResultsA total of 24 patients were treated across five dose levels. Dose-limiting toxicities included transaminases elevation, vomiting, stomatitis, hyperglycemia and diarrhoea. MTD was declared at buparlisib 80 mg/d + lapatinib 1250 mg/d, but toxicities and early treatment discontinuation rate beyond cycle 1 led to select buparlisib 80 mg + lapatinib 1000 mg/d as the RP2D. Main drug-related adverse events included diarrhoea, nausea, skin rash, asthenia, depression, anxiety and transaminases increase. There was no significant evidence for drug–drug PK interaction. Disease control rate was 79% [95% confidence interval [CI] 57–92%], one patient obtained a complete remission, and six additional patients experienced stable disease for ≥ 24 weeks (clinical benefit rate of 29% [95% CI 12–51%]).ConclusionCombining buparlisib and lapatinib in HER2-positive trastuzumab-resistant advanced breast cancer was feasible. Preliminary evidence of antitumour activity was observed in this heavily pre-treated population.Trial registration IDNCT01589861. 相似文献
11.
12.
目的 评价卡培他滨(希罗达)联合长春瑞滨治疗晚期乳腺癌的疗效及毒副反应。方法 24例晚期乳腺癌患者均给予长春瑞滨25 mg/m2,第1,8天;希罗达口服,1 500 mg/m2,2次/d,餐后服用,连续服用14 d。治疗周期为21 d,至少治疗2个周期。结果 本组完全缓解(CR)1例,部分缓解(PR)13例,稳定(SD)7例,进展(PD)3例,总有效率(CR+PR)58.3 %,中位疾病进展时间(TTP)6.5个月。不同转移部位或器官的有效率分别为:肺脏80.0 %(8/10);淋巴结70.0 %(7/10);肝脏54.5 %(6/11);胸壁42.9 %(3/7);骨骼20.0 %(1/5)。Ⅰ和Ⅱ级不良反应为皮肤色素沉着16例,手足综合征15例,恶心呕吐9例,脱发8例,白细胞下降15例。Ⅲ和Ⅳ级不良反应为白细胞下降4例,血红蛋白下降3例。结论 希罗达联合长春瑞滨治疗晚期乳腺癌疗效肯定,患者治疗耐受性良好。 相似文献
13.
Ogura M Mitsumori M Okumura S Yamauchi C Kawamura S Oya N Nagata Y Hiraoka M 《Breast cancer (Tokyo, Japan)》2003,10(4):349-355
BACKGROUND: Breast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases. METHODS: The medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively. RESULTS: The median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control. CONCLUSIONS: Radiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further. 相似文献
14.
Angiogenesis is a key component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for the treatment of cancer. 相似文献
15.
Yonemori K Tsuta K Shimizu C Hatanaka Y Hashizume K Ono M Nakanishi Y Hasegawa T Miyakita Y Narita Y Shibui S Fujiwara Y 《Journal of neuro-oncology》2008,90(2):223-228
The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively
performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor
receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical
staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical
profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical
profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%,
N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical
staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing
treatment strategies, including new molecular-targeted drugs, for brain metastases. 相似文献
16.
BACKGROUND
Brain metastases (BM) are the most common intracranial tumors in adults. To the authors' knowledge, established prognostic factors for survival after the diagnosis of BM in breast cancer patients do not take into account HER–2 status, which may have increasing relevance in the trastuzumab therapy era.METHODS
The authors identified 83 patients with breast cancer and new parenchymal BM diagnosed between January 1, 2001 and December 31, 2005 who were treated at Massachusetts General Hospital. Survival was estimated using the Kaplan‐Meier method and curves were compared using the log‐rank test. A Cox proportional hazards model was used to determine independent predictors of survival.RESULTS
The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER‐2‐positive patients were found to have prolonged survival after BM compared with HER‐2‐negative patients (17.1 months vs 5.2 months). Patients with triple negative disease had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included ≤3 BM, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER‐2 status, number of BM, and local disease status remained independent predictors of survival.CONCLUSIONS
HER‐2 status is a strong predictor of survival after the diagnosis of BM. The survival of breast cancer patients with BM appears to be improving, but a better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk‐benefit ratio of various treatment modalities. Cancer 2008. © 2008 American Cancer Society. 相似文献17.
目的:比较吡咯替尼或来那替尼联合卡培他滨(Pyrotinib/Neratinib+Capecitabine,P/N+C)与拉帕替尼联合卡培他滨(Lapatinib+Capecitabine,L+C)治疗HER-2阳性晚期乳腺癌的疗效性及安全性。方法:检索PubMed、Web of Science、Embase和Cochrane图书馆数据库,选自2005年01月01日截至2021年02月20日的潜在临床研究,合格的研究是前瞻性和注册的临床试验。对无病进展期(progression-free survival,PFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR)具有95%置信区间(confidence interval,CI)的合并优势比和治疗相关不良事件的合并风险比进行Meta分析。结果:本次Meta分析包括3项随机对照试验,共有1 015例患者被纳入本研究。在P/N+C组,6个月PFS[OR=1.87,95%CI(1.44,2.43),P<0.000 01]、12个月PFS[OR=3.87,95%CI(1.95,7.70),P=0.000 1]及ORR[OR=1.70,95%CI(1.10,2.64),P=0.02]较L+C组延长;在常见的治疗相关的不良事件中,除P/N+C组的腹泻发生率较L+C组高[RR=3.10,95%CI(1.80,5.35),P<0.000 1]以外,其余治疗相关不良事件均无显著差异。结论:本Meta分析表明,使用吡咯替尼或来那替尼联合卡培他滨治疗HER-2阳性晚期乳腺癌的疗效更好,并且是一种安全的治疗选择。 相似文献
18.
目的观察培美曲塞联合卡培他滨治疗晚期乳腺癌的临床疗效和不良反应。方法培美曲塞500mg/m2,第1天;卡培他滨2500mg/(m2·d),分2次口服,第1~14天,21d为1个周期。所有病例均接受至少2个周期的化疗。结果 27例患者入组均可评价疗效,CR率3.7%(1/27),PR率22.2%(6/27),SD率37.0%(10/27),PD率37.0%(10/27),有效率25.9%(7/27),临床获益率55.6%(15/27)。中位随访期10个月,中位TTP7个月,中位OS9.5个月,1年生存率为66.7%。主要不良反应为骨髓毒性及手足综合征,Ⅲ度及Ⅳ度白细胞减少为18.5%(5/27)。手足综合征发生率77.7%(21/27),其中,Ⅲ度及Ⅳ度手足综合征发生率为7.4%(2/27)。结论培美曲塞联合卡培他滨方案治疗蒽环类和紫杉类耐药转移性乳腺癌有较好的疗效,患者耐受性好,值得临床进一步研究。 相似文献
19.
20.
Duchnowska R Biernat W Szostakiewicz B Sperinde J Piette F Haddad M Paquet A Lie Y Czartoryska-Arłukowicz B Wysocki P Jankowski T Radecka B Foszczynska-Kłoda M Litwiniuk M Debska S Weidler J Huang W Buyse M Bates M Jassem J 《The oncologist》2012,17(1):26-35