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BACKGROUND: Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. METHODS: For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18-70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0-1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. FINDINGS: From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4-26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7-25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523-0·915; pnon-inferiority<0·0001, psuperiority=0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16-9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76-7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [<1%]), vomiting (13 [11%] vs one [<1%]), musculoskeletal pain (none vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1-4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1-4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. INTERPRETATION: Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. FUNDING: Shanghai Natural Science Foundation.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia , GencitabinaRESUMO
The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.
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Neoplasias da Mama , Metástase Neoplásica , Recidiva Local de Neoplasia , Tumor Filoide , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Quinazolinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Povo Asiático , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina , Classe I de Fosfatidilinositol 3-Quinases , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Diarreia/induzido quimicamente , Progressão da Doença , Intervalo Livre de Doença , Exantema/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Síndrome Mão-Pé/etiologia , Humanos , Lapatinib , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Quinazolinas/efeitos adversos , Receptor ErbB-2/metabolismo , Indução de RemissãoRESUMO
BACKGROUND AND OBJECTIVE: The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome. METHODS: A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied. RESULTS: The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002). CONCLUSIONS: The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Quimioterapia Adjuvante , Irradiação Craniana/métodos , Feminino , Seguimentos , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Receptor ErbB-2/sangue , Receptores de Estrogênio/sangue , Receptores de Progesterona/sangue , Estudos Retrospectivos , Taxa de Sobrevida , Tamoxifeno/uso terapêuticoRESUMO
OBJECTIVE: This study was designed to evaluate the efficacy and toxicity of modified BFM-90 regimen originated from Germany authors in the treatment of Chinese childhood and adolescent lymphoblastic lymphoma. METHODS: Thirty-six untreated lymphoblastic lymphoma patients aged from 3 to 18 years were included, with 1 patient in stage II , 9 in stage III and 26 in stage IV. Of these 36 patients, 28 (77.7%) were diagnosed as T cell phenotype, 26 (72. 2%) were found to have mediastinal mass, 21 (58. 3%) had bone marrow involvement. All patients received chemotherapy of modified BFM-90 regimen consisting of induction remission, central nerve system prophylaxis, re-induction remission and maintenance therapy. Total treatment duration was two years. The difference from standard BFM-90 is that we omitted cranial radiotherapy but gave regular high dose methotrexate (MTX) iv infusion and intrathecal MTX therapy during maintenance therapy period. Kaplan-Meier method was used to evaluate survival rate. RESULTS: Of 36 patients, 32 (88%) achieved complete remission (CR) , 1 (2. 7%) partial remission (PR) with an overall response rate of 90.7%. One patient had disease progression ( DP). Two patients received autologous stem cell transplantation at CR1, and two patients received radiotherapy to mediastinum. Totally, 5 patients relapsed, while 2 of them were still alive after salvage chemotherapy. The other 3 died of tumor progression. Two patients died during induction remission, 1 of fungal septicemia, the other of cerebral hemorrhage; one PR and one DP patient died of disease, therefore, totally 7 patients died at last. Median follow-up time was 28 months. Overall three-year survival rate was 78. 3%. The major toxicity was myelosuppression. CONCLUSION: Modified BFM-90 protocol can improve the efficacy and survival of Chinese childhood and adolescent lymphoblastic lymphoma with tolerable toxicity. However, this modified protocol should only be used in experienced cancer center or hematological unit.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Povo Asiático , Asparaginase/uso terapêutico , Criança , Pré-Escolar , China , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Prednisona/uso terapêutico , Indução de Remissão , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
OBJECTIVE: T-cell non-Hodgkin lymphoma was heterogeneous and relatively high incident in our country. It's response and prognosis were poor. This study was to analyze clinical feature and survival of T-NHL. METHODS: Records of 103 cases with T-NHL, treated from Dec 1998 to Dec 2004 in Cancer Center of Sun Yat-sen University, were retrospectively analyzed. All the patients were classified according to WHO 2001 Classification Criteria. RESULTS: Median age of the whole group was 35 (ranged 2-78) years-old. Of the 103 cases, 68 were male, 35 were female; 25 (24.3%) received chemoradiotherapy, 70 (68.0%) received chemotherapy alone, 3 received radiotherapy and 5 received stem cell transplantation after complete remission. Median survival was 24.1 (ranged 0.8-84) months. 5-year survival rate was 24.3%. Kaplan-Meier analysis discovered that age > 60 years, advanced stage (stage II, IV), extranodal involvement, bulky disease, B symptom, performance status (PS) > or = 2, LDH elevated, hypoalbumin, median-high IPI (IPI > or = 2) were bad to prognosis, but Cox regression found that age > or = 60 years, performance status (PS) > or = 2S, hypoalbumin were the independent bad factors to prognosis. CONCLUSION: This study proved that age, albumin, PS were the independent factors to prognosis.
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Linfoma não Hodgkin/terapia , Linfoma de Células T/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Terapia Combinada , Tratamento Farmacológico , Feminino , Humanos , Linfoma não Hodgkin/patologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia , Estudos Retrospectivos , Transplante de Células-Tronco , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. MATERIAL AND METHODS: A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. RESULTS: During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR- patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. CONCLUSIONS: These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.
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OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.
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Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Adulto , Idoso , Capecitabina , Neoplasias Colorretais/mortalidade , Desoxicitidina/efeitos adversos , Feminino , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Trastuzumab has been the standard treatment in first-line treatment of HER-2-positive advanced breast cancer (H2ABC). This study explored whether the delayed and repeated use of trastuzumab could influence overall survival (OS). A total of 128 patients with H2ABC who had received at least one line of trastuzumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of H2ABC to death. The median OS of initiating trastuzumab in first-line group (n = 56), in the second-line group (n = 32), and the third- or more-line group (n = 40) was 40.6 m, 39.5 m, and 38 m, respectively (P = 0.867). For patients who had received over one line of trastuzumab (n = 46), the median OS was 44 m, and for those receiving only one line (n = 67), it was 27.6 m (P = 0.059). The delayed use of trastuzumab has no negative effect on the OS of patients with H2ABC. There is a trend of improved OS over the repeated use of trastuzumab.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Adulto , Idoso , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Razão de Chances , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , TrastuzumabRESUMO
PURPOSE: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer. METHODS: Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3 months) or metachronous (diagnosed after 3 months of first cancer). SPSS was used for data analysis. RESULTS: 106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T > 5 cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P = 0.000 for both). CONCLUSIONS: Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2 years after the first cancer was significantly worse than synchronous bilateral cancer.
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Povo Asiático/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Adulto , Neoplasias da Mama/metabolismo , China , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós-Menopausa , Prognóstico , Receptor ErbB-2/metabolismo , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: To study the biological and clinicopathological characteristics of neuroendocrine tumors of the kidney (KNETs) for improving the diagnosis and treatment of this diseases. METHODS: The pathological and clinical features of 3 KNET cases treated in Sun Yat-sen University Cancer Center between 1999 and 2010 were summarized, and the the histogenesis, pathological and immunohistochemical characteristics, diagnosis and prognosis of KNETs were analyzed with review of all reported cases worldwide. RESULTS: All the 3 patients had waist masses but without clinical manifestations of carcinoid syndrome, and underwent resection of the tumors. The postoperative pathological diagnosis was carcinoid carcinoma in 2 patients and Wilms tumor with neuroendocrine differentiation in 1 patient. Immunohistochemical examination showed that the tumors were positively stained for cytokeratin and vimentin; positivity for neuron-specific enolase and synaptophysin was found in 2 cases, and chromogranin positivity in 1 case. After the operation, 1 patient received chemotherapy, 1 had biotherapy and radiotherapy, and 1 received no further treatment. During the follow-up from 6 months to 6 years, 1 patient died of tumor metastasis, 1 was lost to follow-up, and 1 showed no recurrence until now. CONCLUSIONS: KNETs has specific pathological characteristics. Abdominal masses, acute loin pain and hematuria are the most common symptoms. A definite diagnosis relies on pathology and immunohistochemistry. For early carcinoid carcinoma, surgical resection is curable, but in advanced cases, the prognosis is poor and comprehensive therapy is recommended.
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Neoplasias Renais , Tumores Neuroendócrinos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate general and clinicopathological characteristics of male breast cancer and analyzed the factors affecting the outcomes of the patients based on the data from a single institution. METHODS: Twenty-five male breast cancer patients treated at Sun Yet-sen University Cancer Center between January 1, 2000 and April 30, 2011 were included into the study. The patients were followed up for 1 to 90 months with a median follow-up of 51 months. The general and clinicopathological characteristics including family history, age, smoking, alcohol drinking, site of tumor, location of tumor, histological type, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), Ki-67, vascular endothelial growth factor (VEGF), P53 expression, neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, tumor size, lymph node status, distant metastasis and TNM stage were investigated by univariate analysis to evaluate the impact of these factors on patient survival. RESULTS: The 5-year survival rate was 66.5% in these patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage were significant predictors for the overall survival. Patients receiving adjuvant endocrine therapy tended to have a better overall survival, though this was not supported statistically (P=0.086). However, patients with neoadjuvant chemotherapy had a poorer overall survival than those without it (P=0.000). Patients in stages I and II had better overall survival than those in stages III and IV (P=0.000). CONCLUSION: The 5-year survival rate was 66.5% in these male breast cancer patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage are significant predictors of the overall patient survival.
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Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/tratamento farmacológico , Seguimentos , Humanos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND & OBJECTIVE: HER2 is overexpressed in approximately 20.0% to 30.0% of breast cancer patients. This alteration is associated with poor prognosis, and may affect response to hormonal therapy and chemotherapy. Chemotherapy combined with trastuzumab can significantly improve the treatment efficacy and survival of Her-2/neu overexpressing breast cancer patients. Docetaxel is an effective drug used for metastatic breast cancer recently. This study was to evaluate the efficacy and toxicity of trastuzumab combined with docetaxel in the treatment for metastatic breast cancer patients with overexpressed Her-2/neu. METHODS: Twenty-two metastatic breast cancer patients with overexpressed HER2/neu were entered into the study. Trastuzumab and docetaxel (75 mg/m(2)) were administrated on day 1 and repeated every 21 days. The initial dose of trastuzumab was 8 mg/kg and subsequent doses were 6 mg/kg. RESULTS: Overall 96 cycles were administrated to the 22 patients (medium three cycles per patient, range 2-6 cycles). All cases were evaluable. The overall response rate was 63.6% (14/22). Two patients achieved complete response (CR), 12 patients achieved partial response (PR), four patients achieved stable disease (SD), and four patients had progressive disease (PD). The median time to progression was 5.4 months. One year overall survival was 59.0%. The major toxicity was myelosuppression. A few patients had fever at first infusion of trastuzumab and minor heart failure. CONCLUSION: Trastuzumab combined with docetaxel is an effective and well-tolerated therapy for Her-2/neu overexpressing metastatic breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Docetaxel , Exantema/induzido quimicamente , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Indução de Remissão , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trombocitopenia/induzido quimicamente , TrastuzumabRESUMO
OBJECTIVE: To evaluate the efficacy and toxicity in patients with HER2 overexpressing metastatic breast cancer. METHODS: Twenty-one patients with HER2 overexpressing metastatic breast cancer entered into the study. Trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days. RESULTS: Overall 56 cycles were given to the 21 patients enrolled into the study (mean 2, range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one patient achieved complete response (CR), six patients achieved partial response (PR), four patients achieved stable disease (SD), ten patients achieved progressive disease (PD)]. The median time to progression was 3.5 months. One year overall survival was 33%. The major toxicity was myelosuppression and peripheral neuritis. A few patients were observed with fever and lower grade cardiac failure. CONCLUSION: The combination of trastuzumab and vinorelbine is an effective and well tolerated therapy in patients with pretreated metastatic breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Trastuzumab , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina , Vômito/induzido quimicamenteRESUMO
BACKGROUND & OBJECTIVE: It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. METHODS: Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. RESULTS: Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. CONCLUSIONS: The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Quimioterapia Adjuvante , Feminino , Febre/induzido quimicamente , Testes de Função Cardíaca , Humanos , Mastectomia , Pessoa de Meia-Idade , Período Pós-Operatório , Receptor ErbB-2/sangue , Estudos Retrospectivos , Estremecimento , Volume Sistólico , TrastuzumabRESUMO
BACKGROUND & OBJECTIVE: Burkitt's lymphoma is a kind of highly aggressive B-cell lymphoma. Its clinical characteristics are different between the endemic areas in Africa and the sporadic areas in America and Europe. There is no large-scale report concerning Burkitt's lymphoma in China yet. This study was to summarize the characteristics of Burkitt's lymphoma in China. METHODS: Clinical data of 69 Burkitt's lymphoma patients, treated from May 1985 to May 2007 in Cancer Center of Sun Yat-sen University, were analyzed. RESULTS: Of the 69 patients, 44 were men and 25 were women, with a median age of 7 (range, 2-72); 5 were at stage I, 9 at stage II, 21 at stage III, and 34 at stage IV, advanced stage (stages III and IV) accounted for 55 (79.7%) patients. Abdomen (63.8%), cervical lymph nodes (68.1%) and faciomaxillary-oropharynx (34.8%) were the most common involved sites. Bone marrow (21.9%) and central nervous system (17.4%) could also be involved. B symptoms were found in 34 patients. Serum lactate dehydrogenase (LDH) level was elevated in 42 of 58 patients, while serum uric acid level was elevated in 13 of 56 patients. Hepatitis B virus (HBV) infection was found in 6 of 57 patients, Epstain-Barr virus (EBV) infection in 7 of 13 patients, human immunodeficiency virus (HIV) infection in 0 of 51 patients. Short-term and high intensive chemotherapy with central nervous system prophylaxis could improve the prognosis. CONCLUSION: The clinical characteristics of these 69 Burkitt's lymphoma patients are much similar to those from sporadic areas, but the median age is lower, and the most common involved sites are cervical lymph nodes, abdomen and faciomaxillary-oropharynx.
Assuntos
Linfoma de Burkitt/tratamento farmacológico , Adolescente , Adulto , Idoso , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Criança , Pré-Escolar , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E(2)17betaG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/patologia , Quinazolinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Quinazolinas/administração & dosagem , Quinazolinas/farmacocinética , Transfecção , Carga Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND & OBJECTIVE: Chemotherapy is one of major treatments of metastatic breast cancer. Anthracyclines and taxanes are usually considered as the most active agents in breast cancer and are often used as adjuvant or first-line therapy. Gemcitabine and vinorelbine are active agents in breast cancer. This study was to evaluate the efficacy of gemcitabine combined vinorelbine on the patients with metastatic breast cancer, who had previously received treatment of anthracyclines and/or taxanes. METHODS: Thirty-four patients with metastatic breast cancer, who had been previously treated with anthracyclines alone or with taxanes, were enrolled. The patients received 30-minute intravenous injection of gemcitabine (1 000 mg/m(2)) and intravenous bolus injection of vinorelbine(25 mg/m(2)) on Days 1 and 8; the regimen was repeated every 21 days. RESULTS: A total of 109 cycles were given to the 34 patients (median, 3 cycles; range, 1-6 cycles). The treatment responses were evaluable in all patients. Of the 34 patients, 9 achieved partial remission (PR), 19 had stable disease (SD), 6 had progressive disease (PD)û the response rate was 26.47%. The median time to progression was 5.4 months. The median overall survival was 17.8 months. The 1-year overall survival rate was 68% [95% confidence interval (CI): 50%-86%], the 2-year overall survival rate was 46% (95% CI: 26%-66%). The major adverse events were grade I-II myelosuppression, peripheral neurologic toxicities, nausea and vomiting. Some patients had rash and hepatic dysfunction. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and well tolerated regimen for the patients with metastatic breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Neutropenia/induzido quimicamente , Indução de Remissão , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Vômito/induzido quimicamente , GencitabinaRESUMO
BACKGROUND & OBJECTIVE: The prognosis of breast cancer patients with liver metastasis is poor. How to improve treatment efficacy and prolong survival of these patients is a challenge in clinic. This study was to explore the efficacy of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast cancer patients with liver metastasis, and analyze prognostic factors. METHODS: Clinical data of 98 breast cancer patients with liver metastasis, treated from 1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. The prognostic factors correlated to clinical features and treatment approaches were determined using Cox multivariate model. RESULTS: The total response rate was 45.9% for all patients, 48.6% for the 74 patients received systemic chemotherapy, 23.1% for the 13 patients received TACE, and 54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%, 19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months), and the progression-free survival was 6 months (0-50 months). CONCLUSION: The combination of systemic chemotherapy and TACE may prolong the survival of breast cancer patients with liver metastasis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma (NHL) and often involves bone marrow and central nerve system. The efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents, and observe the survival status. METHODS: From Oct. 1999 to Nov. 2006, 31 untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20 (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1 (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%) at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage, lactate dehydrogenase (LDH) level and treatment response, these patients were divided into low, moderate and high risk groups. They received modified B-NHL-BFM-90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD-cytarabine and intrathecal injection. RESULTS: One patient died of tumor lysis syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30 patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial remission (PR), 2 (6.7%) had progressive disease (PD)û 1 had tumor relapse. Grade 3-4 myelosuppression occurred in most patients and were recovered by active support care and did not affect next course of chemotherapy. At a median follow-up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and 70.0% for high risk group. CONCLUSIONS: Modified B-NHL-BFM-90 protocol can improve the responses and survival of Burkitt's lymphoma in Chinese children and adolescents, with tolerable toxicity. It should be used in the experienced cancer center and hematological unit.