Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.917
Filtrar
1.
Anticancer Res ; 40(12): 6915-6921, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288585

RESUMO

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Biomarcadores , Docetaxel/uso terapêutico , Esquema de Medicação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Qualidade de Vida , Retratamento , Taxoides/efeitos adversos , Resultado do Tratamento
2.
Lancet Oncol ; 21(11): 1455-1464, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152285

RESUMO

BACKGROUND: In early-stage HER2-positive breast cancer, escalation or de-escalation of systemic therapy is a controversial topic. As an aid to treatment decisions, we aimed to develop a prognostic assay that integrates multiple data types for predicting survival outcome in patients with newly diagnosed HER2-positive breast cancer. METHODS: We derived a combined prognostic model using retrospective clinical-pathological data on stromal tumour-infiltrating lymphocytes, PAM50 subtypes, and expression of 55 genes obtained from patients who participated in the Short-HER phase 3 trial. The trial enrolled patients with newly diagnosed, node-positive, HER2-positive breast cancer or, if node negative, with at least one risk factor (ie, tumour size >2 cm, histological grade 3, lymphovascular invasion, Ki67 >20%, age ≤35 years, or hormone receptor negativity), and randomly assigned them to adjuvant anthracycline plus taxane-based combinations with either 9 weeks or 1 year of trastuzumab. Trastuzumab was administered intravenously every 3 weeks (8 mg/kg loading dose at first cycle, and 6 mg/kg thereafter) for 18 doses or weekly (4 mg/kg loading dose in the first week, and 2 mg/kg thereafter) for 9 weeks, starting concomitantly with the first taxane dose. Median follow-up was 91·4 months (IQR 75·1-105·6). The primary objective of our study was to derive and evaluate a combined prognostic score associated with distant metastasis-free survival (the time between randomisation and distant recurrence or death before recurrence), an exploratory endpoint in Short-HER. Patient samples in the training dataset were split into a training set (n=290) and a testing set (n=145), balancing for event and treatment group. The training set was further stratified into 100 iterations of Monte-Carlo cross validation (MCCV). Cox proportional hazard models were fit to MCCV training samples using Elastic-Net. A maximum of 92 features were assessed. The final prognostic model was evaluated in an independent combined dataset of 267 patients with early-stage HER2-positive breast cancer treated with different neoadjuvant and adjuvant anti-HER2-based combinations and from four other studies (PAMELA, CHER-LOB, Hospital Clinic, and Padova) with disease-free survival outcome data. FINDINGS: From Short-HER, data from 435 (35%) of 1254 patients for tumour size (T1 vs rest), nodal status (N0 vs rest), number of tumour-infiltrating lymphocytes (continuous variable), subtype (HER2-enriched and basal-like vs rest), and 13 genes composed the final model (named HER2DX). HER2DX was significantly associated with distant metastasis-free survival as a continuous variable (p<0·0001). HER2DX median score for quartiles 1-2 was identified as the cutoff to identify low-risk patients; and the score that distinguished quartile 3 from quartile 4 was the cutoff to distinguish medium-risk and high-risk populations. The 5-year distant metastasis-free survival of the low-risk, medium-risk, and high-risk populations were 98·1% (95% CI 96·3-99·9), 88·9% (83·2-95·0), and 73·9% (66·0-82·7), respectively (low-risk vs high-risk hazard ratio [HR] 0·04, 95% CI 0·0-0·1, p<0·0001). In the evaluation cohort, HER2DX was significantly associated with disease-free survival as a continuous variable (HR 2·77, 95% CI 1·4-5·6, p=0·0040) and as group categories (low-risk vs high-risk HR 0·27, 0·1-0·7, p=0·005). 5-year disease-free survival in the HER2DX low-risk group was 93·5% (89·0-98·3%) and in the high-risk group was 81·1% (71·5-92·1). INTERPRETATION: The HER2DX combined prognostic score identifies patients with early-stage, HER2-positive breast cancer who might be candidates for escalated or de-escalated systemic treatment. Future clinical validation of HER2DX seems warranted to establish its use in different scenarios, especially in the neoadjuvant setting. FUNDING: Instituto Salud Carlos III, Save the Mama, Pas a Pas, Fundación Científica, Asociación Española Contra el Cáncer, Fundación SEOM, National Institutes of Health, Agenzia Italiana del Farmaco, International Agency for Research on Cancer, and the Veneto Institute of Oncology, and Italian Association for Cancer Research.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Trastuzumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/efeitos adversos , Resultado do Tratamento
3.
Int J Nanomedicine ; 15: 8151-8166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132699

RESUMO

Conventional taxanes are used as cornerstone of the chemotherapeutical treatment for a variety of malignancies. Nevertheless, a large proportion of patients do not benefit from their treatment while they do suffer from severe adverse events related to the solvent or to the active compound. Cremophor EL and polysorbate 80 free formulations, conjugates, oral formulations and different types of drug delivery systems are some examples of the several attempts to improve the treatment with taxanes. In this review article, we discuss recent clinical developments of nanomediated drug delivery systems of taxanes for the treatment of cancer. Targeting mechanisms of drug delivery systems and characteristics of the most commonly used taxane-containing drug delivery systems in the clinical setting will be discussed in this review.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/administração & dosagem , Taxoides/administração & dosagem , Animais , Antineoplásicos/uso terapêutico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Taxoides/farmacocinética , Taxoides/uso terapêutico
4.
Nat Commun ; 11(1): 5848, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203866

RESUMO

Evidence has recently emerged that many clinical cancer drug combinations may derive their efficacy from independent drug action (IDA), where patients only receive benefit from the single most effective drug in a drug combination. Here we present IDACombo, an IDA based method to predict the efficacy of drug combinations using monotherapy data from high-throughput cancer cell line screens. We show that IDACombo predictions closely agree with measured drug combination efficacies both in vitro (Pearson's correlation = 0.93 when comparing predicted efficacies to measured efficacies for >5000 combinations) and in a systematically selected set of clinical trials (accuracy > 84% for predicting statistically significant improvements in patient outcomes for 26 first line therapy trials). Finally, we demonstrate how IDACombo can be used to systematically prioritize combinations for development in specific cancer settings, providing a framework for quickly translating existing monotherapy cell line data into clinically meaningful predictions of drug combination efficacy.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos de Anilina/administração & dosagem , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Bases de Dados de Produtos Farmacêuticos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Reprodutibilidade dos Testes , Sulfonamidas/administração & dosagem , Taxoides/administração & dosagem , Fluxo de Trabalho
5.
Lancet Oncol ; 21(11): 1513-1525, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926841

RESUMO

BACKGROUND: In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study. METHODS: CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice-web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form [BPI-SF]) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and the EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling. FINDINGS: Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6-13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE-NE) with cabazitaxel and 8·5 months (4·9-NE) with abiraterone or enzalutamide (hazard ratio [HR] 0·55, 95% CI 0·32-0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0-NE) with cabazitaxel and 16·7 months (10·8-NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35-1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3-NE) with cabazitaxel and 8·9 months (6·3-NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44-1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060). INTERPRETATION: Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor. FUNDING: Sanofi.


Assuntos
Androstenos/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Androgênios/genética , Androstenos/efeitos adversos , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Taxoides/efeitos adversos , Resultado do Tratamento
6.
Anticancer Res ; 40(9): 5255-5261, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878814

RESUMO

BACKGROUND/AIM: Treatment of recurrent platinum-resistant ovarian cancer remains challenging due to the development of resistance to chemotherapy. Cabazitaxel is a new taxane that has demonstrated beneficial effect in prostate cancer patients resistant to docetaxel. Therefore, it could be anticipated to possibly also have an effect on chemotherapy resistant ovarian cancer. PATIENTS AND METHODS: Twenty-six patients with chemotherapy-resistant epithelial ovarian cancer, fallopian tube or peritoneal cancer were treated with cabazitaxel at a dose of 25 mg/m2 (on day 1 of each 3-week cycle), until progression or inacceptable toxicity, between September 2015 and April 2018. The fraction of patients without progression after three months of treatment was the primary endpoint. Prophylaxis with granulocyte colony-stimulating factor (G-CSF) was prescribed to all patients. RESULTS: The median number of cabazitaxel infusions was 4 (range=1-18). In general, cabazitaxel was well-tolerated. The fraction of patients alive and without progression after 3 months of treatment was 54% (14/26). The response rate was 46% (12/26) according to the Gynecological Cancer Intergroup (GCIG) criteria for CA125. Partial response (PR), evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST), was found in 4/26 patients (15%). By intention-to-treat analysis, the median progression-free survival (PFS) was 3.9 months (95% CI=1.9-4.4) using the combination of CA125 or RECIST (whichever came first), while the median overall survival (OS) was 8.4 months (95% CI=5.1-11.0). CONCLUSION: Cabazitaxel holds promise as a drug in recurrent platinum-resistant ovarian cancer. It demonstrated efficacy and in general, the toxicity was manageable.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Qualidade de Vida , Recidiva , Retratamento , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
7.
Int J Nanomedicine ; 15: 5333-5344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801692

RESUMO

Purpose: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment. Methods: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo. Results: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile. Conclusion: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Soroalbumina Bovina/administração & dosagem , Taxoides/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Cromatografia Líquida , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Docetaxel , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias da Próstata/diagnóstico por imagem , Ratos Sprague-Dawley , Soroalbumina Bovina/farmacocinética , Espectrometria de Massas em Tandem , Taxoides/farmacocinética , Distribuição Tecidual
8.
Sci Rep ; 10(1): 13241, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764734

RESUMO

The aims of this study were to investigate the impact of the relative dose intensity (RDI) of chemotherapy on disease-free survival (DFS) and overall survival (OS), to identify the optimal RDI cut-off points with the docetaxel, epirubicin and cyclophosphamide (TEC) regimen for stage I-III breast cancer patients and to explore the adverse events in these patients. To achieve this, we performed a retrospective analysis of breast cancer patients treated at the First Affiliated Hospital of Chongqing Medical University in 2011. The results showed that among 293 patients with the TEC regimen, 85% and 80% were the cut-off points at which a high RDI was associated with better overall survival (HR = 2.04; 95% CI 1.13, 3.70; p = 0.02) and disease-free survival (HR = 1.97; 95% CI 1.14-3.42; p = 0.02), respectively. Among 169 HR(+) patients, 80% was the cut-off point for DFS (HR = 2.33; 95% CI 1.07-5.08; p = 0.03), and 85% was the cut-off point for OS (HR = 3.00; 95% CI 1.24-7.26; p = 0.02). Among 105 HR(-) patients, 80% was the cut-off point for OS (HR = 2.86; 95% CI 1.05-7.80; p = 0.04). Of 293 patients, neutropenia, nausea, and vomiting were found to be correlated with the level of RDI. In conclusion, a higher RDI of chemotherapy is associated with better survival but with a higher probability of causing adverse events. To optimize survival benefits, the RDI should be maintained ≥ 85% for HR(+) patients and ≥ 80% for HR(-) patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Resultado do Tratamento
9.
Value Health ; 23(6): 768-774, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32540235

RESUMO

OBJECTIVE: We investigated the quantification of the response shift-adjusted treatment effect on quality-of-life (QOL) data in a randomized controlled trial of taxane versus S-1 for patients with metastatic breast cancer (SELECT-BC). METHODS: This study was a secondary data analysis of a previously published trial. The response shift-adjusted treatment effect on health-related QOL (HRQOL) data measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was estimated using structural equation modeling techniques in addition to quantifying the "true" treatment effect. Measurement invariances in the values of the common factor loadings, intercepts, and residual variances between before treatment and at the 3-, 6-, and 12-month visits were considered the response shift effects. RESULTS: In the taxane group, we observed positive recalibration effects for role functioning and positive reprioritization and negative recalibration effects for emotional functioning. The observed change of -4.56 for role functioning comprised +2.26 response shifts and -6.82 "true" change. The observed change of +9.41 for emotional functioning comprised +12.43 response shifts and -1.17 "true" change. In the S-1 group, we observed positive reprioritization and negative recalibration effects for emotional functioning and positive reprioritization effects for social functioning. The observed change of +10.54 for emotional functioning comprised +10.07 response shifts and +0.47 "true" change. The observed change of +2.43 for social functioning comprised +3.50 response shifts and -1.07 "true" change. CONCLUSION: Detailed analysis of the response shift effects will improve the evaluation reliability of observed HRQOL data during clinical trials.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ácido Oxônico/administração & dosagem , Qualidade de Vida , Taxoides/administração & dosagem , Tegafur/administração & dosagem , Adulto , Idoso , Combinação de Medicamentos , Feminino , Humanos , Análise de Classes Latentes , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Expert Opin Pharmacother ; 21(12): 1431-1448, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32469248

RESUMO

INTRODUCTION: Metastatic castration-resistant prostate cancer (CRPC) is a potentially symptomatic disease with an eventual lethal outcome. Novel pharmaceutical agents are continuously studied with encouraging results in CRPC. AREAS COVERED: In this perspective, the authors present established and promising pharmacotherapeutic strategies for the management of CRPC; both with and without metastases. Apart from the different treatment strategies, the authors present the relevant sequence of treatment through disease progression. EXPERT OPINION: Usually, docetaxel should be considered the first line treatment in mCRPC. Abiraterone acetate (AA) plus prednisone or enzalutamide (ENZ) could be alternative treatments in chemotherapy naïve patients. Sipuleucel-T has been approved for the treatment of asymptomatic or minimally symptomatic mCRPC. Ra-223 has been approved for patients with mCRPC with symptomatic bone metastases (not visceral metastases). Cabazitaxel has been approved as the second line treatment to docetaxel in mCRPC. No differences in the overall survival has been observed between sequences starting with docetaxel versus AA/ENZ. Between AA-to-ENZ and ENZ-to-AA sequence, the AA-to-ENZ sequence appeared to be more favorable than the ENZ-to-AA regarding progression-free survival but not overall survival. Carbazitaxel seemed to retain its activity regardless of the treatment sequence. Of note, ENZ and apalutamide have been approved in non-metastatic CRPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/uso terapêutico , Androstenos/administração & dosagem , Androstenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Humanos , Masculino , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/mortalidade , Rádio (Elemento)/administração & dosagem , Rádio (Elemento)/uso terapêutico , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Extratos de Tecidos/administração & dosagem , Extratos de Tecidos/uso terapêutico
11.
Mol Cancer Res ; 18(9): 1379-1391, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32471883

RESUMO

Ovarian cancer is an aggressive disease that affects about 300,000 patients worldwide, with a yearly death count of about 185,000. Following surgery, treatment involves adjuvant or neoadjuvant administration of taxane with platinum compounds cisplatin or carboplatin, which alkylate DNA through the same chemical intermediates. However, although platinum-based therapy can cure patients in a number of cases, a majority of them discontinues treatment owing to side effects and to the emergence of resistance. In this study, we focused on resistance to cisplatin and investigated whether metabolic changes could be involved. As models, we used matched pairs of cisplatin-sensitive (SKOV-3 and COV-362) and cisplatin-resistant (SKOV-3-R and COV-362-R) human ovarian carcinoma cells that were selected in vitro following exposure to increasing doses of the chemotherapy. Metabolic comparison revealed that resistant cells undergo a shift toward a more oxidative metabolism. The shift goes along with a reorganization of the mitochondrial network, with a generally increased mitochondrial compartment. More functional mitochondria in cisplatin-resistant compared with cisplatin-sensitive cells were associated to enzymatic changes affecting either the electron transport chain (SKOV-3/SKOV-3-R model) or mitochondrial coupling (COV-362/COV-362-R model). Our findings further indicate that the preservation of functional mitochondria in these cells could be due to an increased mitochondrial turnover rate, suggesting mitophagy inhibition as a potential strategy to tackle cisplatin-resistant human ovarian cancer progression. IMPLICATIONS: Besides classical mechanisms related to drug efflux and target modification, we report that preserving functional mitochondria is a strategy used by human ovarian cancer cells to resist to cisplatin chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Cisplatino/farmacologia , Metabolismo Energético , Neoplasias Ovarianas/tratamento farmacológico , Transdução de Sinais , Animais , Autofagia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma/virologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos Nus , Mitocôndrias/metabolismo , Mitofagia , Neoplasias Ovarianas/virologia , Oxirredução , Taxoides/administração & dosagem
12.
J Surg Oncol ; 122(2): 164-169, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32291774

RESUMO

BACKGROUND AND OBJECTIVES: Marking positive lymph nodes (LNs) before neoadjuvant chemotherapy (NAC) may improve the accuracy of sentinel lymph node biopsy (SLNB). The aim of this study was to determine the feasibility of marking LNs with 4% carbon microparticle suspension (CMS) before NAC and to evaluate if this technique would improve the SLNB identification rate. METHODS: A prospective study of patients with cT1-T4, cN1-N2 breast cancer who underwent US-guided fine-needle aspiration biopsy (FNAB) of suspected LNs and concomitant marking with 4% CMS was performed. After NAC, LNs marked with 4% CMS and those marked with Patent Blue V dye (PBV) were identified and resected. RESULTS: Of the 123 patients included, 74 (60.1%) had positive LNs at FNAB. During axillary surgery, 4% CMS was identified in 121 of 123 patients (98.3%) and blue sentinel LNs in 91% (112 of 123 patients) (P = .0103). Comparing isolated results of PBV and 4%CMS + PBV, the association was better in identifying positive LNs (72.2% vs 97.7%) (P = .02). CONCLUSION: The association of 4% CMS and PBV is feasible and significantly increased the identification rate of positive LNs. 4% CMS may play an important role as a complementary technique in patients submitted to NAC.


Assuntos
Neoplasias da Mama/patologia , Carbono/administração & dosagem , Linfonodo Sentinela/patologia , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Tamanho da Partícula , Estudos Prospectivos , Linfonodo Sentinela/diagnóstico por imagem , Taxoides/administração & dosagem
13.
Breast Cancer Res Treat ; 181(1): 87-96, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32232698

RESUMO

PURPOSE: To prospectively compare HRQoL effects of two modern adjuvant chemotherapy breast cancer treatment regimens at six time-points up to 16 months after random assignment. METHODS: The open-label, randomized, Phase 3 "Panther trial" was conducted between February 2007 and September 2011. 760 women, aged 65 years and younger, after surgery for non-metastatic node-positive or high-risk node-negative breast cancer were randomized 1:1 to the experimental group (four cycles of tailored and dose-dense adjuvant epirubicin and cyclophosphamide/2 weeks followed by four cycles of tailored dose-dense docetaxel/2 weeks) or standard group (three cycles of fluorouracil and epirubicin-cyclophosphamide/3 weeks followed by three cycles of docetaxel/3 weeks). HRQoL was assessed at all Swedish centres using EORTC QLQ-C30 and EORTC QLQ-BR23 at six points during 16 months before randomization. RESULTS: Response rates to questionnaires were highest at baseline 728/780 (93%) and lowest 16 months after randomization, 557/750 (74%). HRQoL declined during treatment in both groups. At the end of treatment, the experimental group reported statistically significantly lower HRQoL (P < 0.001) than the standard group on global health status, physical functioning, role functioning, social functioning, fatigue, sexual functioning, and systemic therapy effects. No differences were found for emotional functioning, body image, and arm and breast symptoms. There were no statistically significant differences between the groups at the first follow-up and at subsequent assessments. HRQoL levels at the 16-month follow-up were similar to baseline values. CONCLUSIONS: Negative HRQoL impact of the dose-dense and tailored strategy appears to be prominent during treatment, but HRQoL recover once treatment ends. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Qualidade de Vida , Adolescente , Adulto , Idoso , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Suécia , Taxoides/administração & dosagem , Fatores de Tempo , Adulto Jovem
14.
J Urol ; 204(2): 247-253, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32118506

RESUMO

PURPOSE: For patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer, multi-agent intravesical trials have been limited. In this study we investigate the safety of intravesical cabazitaxel, gemcitabine and cisplatin in the salvage setting. MATERIALS AND METHODS: This was a dose escalation, drug escalation trial for patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer who declined or were ineligible for radical cystectomy. All patients underwent a 6-week induction regimen of sequentially administered cabazitaxel, gemcitabine and cisplatin. Complete response was defined as no cancer on post-induction transurethral bladder tumor resection and negative urine cytology, while partial response allowed for positive cytology. Responders continued with maintenance cabazitaxel and gemcitabine monthly for the first year and bimonthly for the second year. RESULTS: A total of 18 patients were enrolled. Mean age was 71 years, median followup was 27.8 months (range 16.3 to 46.9) and mean number of previous rounds of intravesical therapies before trial enrollment was 3.7. Nine patients (50%) had received intravesical chemotherapy after bacillus Calmette-Guérin and 7 (39%) were previously treated in a phase I clinical trial setting. At enrollment 6 (33%) subjects had T1 disease and 13 (72%) had carcinoma in situ. There were no dose limiting toxicities. Initial partial and complete response rates were 94% and 89%, respectively. At 1 year recurrence-free survival was 0.83 (range 0.57 to 0.94) and at 2 years estimated recurrence-free survival was 0.64 (0.32 to 0.84). CONCLUSIONS: In this high risk and highly pretreated cohort of bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer cases combination intravesical cabazitaxel, gemcitabine and cisplatin was a well tolerated and potentially effective regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Taxoides/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/administração & dosagem , Carcinoma de Células de Transição/patologia , Desoxicitidina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia
15.
Int J Radiat Oncol Biol Phys ; 106(5): 939-947, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32029346

RESUMO

PURPOSE: Cabazitaxel has been demonstrated to improve the overall survival for men with metastatic castrate-resistant prostate cancer. The purpose of this study was to determine the maximum tolerated dose for concurrent cabazitaxel with androgen deprivation and intensity modulated radiation therapy in men with high-risk prostate cancer. METHODS AND MATERIALS: Twenty men were enrolled in this institutuional review board-approved phase I clinical trial using a 3 + 3 design. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. RESULTS: With a median follow-up time of 56 months, the maximum tolerated dose of concurrent cabazitaxel was 6 mg/m2. The 5-year biochemical disease-free survival was 73%, despite 75% of patients having very high risk prostate cancer per the National Comprehensive Cancer Network guidelines. Four patients were unable to complete chemotherapy owing to dose-limiting toxicities (eg, rectal bleeding, diarrhea, and elevated transaminase). There was no significant minimally important difference in Expanded Prostate Index Composite patient-reported outcomes for either the urinary or bowel domains; however, there was a significant decrease in the sexual domain. CONCLUSIONS: This is the first clinical trial of prostate cancer to report on the combination of cabazitaxel and radiation therapy. The maximum tolerated dose of concurrent cabazitaxel with radiation and androgen deprivation therapy was determined to be 6 mg/m2. Despite the aggressive nature of the disease, robust biochemical control was observed.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioterapia de Intensidade Modulada , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Terapia Combinada , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade da Assistência à Saúde , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
16.
Cancer Res ; 80(8): 1693-1706, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32054769

RESUMO

A significant therapeutic challenge for patients with cancer is resistance to chemotherapies such as taxanes. Overexpression of LIN9, a transcriptional regulator of cell-cycle progression, occurs in 65% of patients with triple-negative breast cancer (TNBC), a disease commonly treated with these drugs. Here, we report that LIN9 is further elevated with acquisition of taxane resistance. Inhibiting LIN9 genetically or by suppressing its expression with a global BET inhibitor restored taxane sensitivity by inducing mitotic progression errors and apoptosis. While sustained LIN9 is necessary to maintain taxane resistance, there are no inhibitors that directly repress its function. Hence, we sought to discover a druggable downstream transcriptional target of LIN9. Using a computational approach, we identified NIMA-related kinase 2 (NEK2), a regulator of centrosome separation that is also elevated in taxane-resistant cells. High expression of NEK2 was predictive of low survival rates in patients who had residual disease following treatment with taxanes plus an anthracycline, suggesting a role for this kinase in modulating taxane sensitivity. Like LIN9, genetic or pharmacologic blockade of NEK2 activity in the presence of paclitaxel synergistically induced mitotic abnormalities in nearly 100% of cells and completely restored sensitivity to paclitaxel, in vitro. In addition, suppressing NEK2 activity with two distinct small molecules potentiated taxane response in multiple in vivo models of TNBC, including a patient-derived xenograft, without inducing toxicity. These data demonstrate that the LIN9/NEK2 pathway is a therapeutically targetable mediator of taxane resistance that can be leveraged to improve response to this core chemotherapy. SIGNIFICANCE: Resistance to chemotherapy is a major hurdle for treating patients with cancer. Combining NEK2 inhibitors with taxanes may be a viable approach for improving patient outcomes by enhancing mitotic defects induced by taxanes alone.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mitose/efeitos dos fármacos , Quinases Relacionadas a NIMA/antagonistas & inibidores , Proteínas Nucleares/antagonistas & inibidores , Paclitaxel/farmacologia , Taxoides/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteínas Supressoras de Tumor/antagonistas & inibidores , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Senescência Celular , Centrossomo/enzimologia , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Xenoenxertos , Humanos , Mitose/genética , Quinases Relacionadas a NIMA/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Paclitaxel/administração & dosagem , Taxa de Sobrevida , Taxoides/administração & dosagem , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Ensaio Tumoral de Célula-Tronco , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima
17.
BMC Cancer ; 20(1): 89, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013967

RESUMO

BACKGROUND: We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. METHODS: The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , DNA Viral/genética , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
Oncol Rep ; 43(3): 965-974, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020211

RESUMO

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20­30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Paclitaxel/administração & dosagem , Idoso , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Camundongos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , RNA Mensageiro/genética , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Breast Cancer Res Treat ; 180(3): 597-609, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32100144

RESUMO

PURPOSE: In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC). METHODS: Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints. RESULTS: The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators. CONCLUSIONS: The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Feminino , Humanos , Terapia de Alvo Molecular , Metanálise em Rede , Taxoides/administração & dosagem , Trastuzumab/administração & dosagem , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA