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1.
Bull Cancer ; 108(3): 266-271, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33423777

RESUMO

INTRODUCTION: Taxanes are widely used in medical oncology. The aim of our study was to report and analyze the toxicity features of these drugs in Tunisian patients and to determine their impact on treatment response. METHODS: Our retrospective study concerned 90 patients treated by taxanes in a medical oncology unit, from January 2014 to January 2017. We collected their epidemiologic and anatomo-clinical data and we detailed toxicity features including types grades and impact on tumor response. RESULTS: Median age was 46 years. 80% of patients had breast cancer. Tumors were metastatic in 23.3% of cases. Nail toxicity was observed in 100% of patients. Grade I-II digestive toxicity was observed in 54.4% of cases. Hematological toxicity was noted in 42.2% of patients and it reached grade III-IV in five patients. Neurological toxicity occurred in 31% of patients and was grade III-IV in 6 cases. Alopecia was observed in 60% of patients. Fatigue was noted in 57.8% of patients. Myalgia was observed in 42.2% of patients. Toxicity did not affect the response to treatment. CONCLUSION: The taxanes' toxicity profile in Tunisian patients is characterized by more frequent digestive and nail toxicities and less frequent hematological toxicities, dose reduction and treatment delays than other populations.


Assuntos
Antineoplásicos/efeitos adversos , Taxoides/efeitos adversos , Adulto , Idoso , Alopecia/induzido quimicamente , Alopecia/epidemiologia , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cisplatino/administração & dosagem , Doenças do Sistema Digestório/induzido quimicamente , Doenças do Sistema Digestório/epidemiologia , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/induzido quimicamente , Doenças da Unha/epidemiologia , Doenças do Sistema Nervoso/induzido quimicamente , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Taxoides/administração & dosagem , Tunísia/epidemiologia
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.
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
4.
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
5.
Ann Allergy Asthma Immunol ; 125(3): 325-333.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32353405

RESUMO

BACKGROUND: Hypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them. OBJECTIVE: To evaluate the safety and efficacy of the Brigham and Women's Hospital's 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins. METHODS: We conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions. RESULTS: A total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive. CONCLUSION: This large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/imunologia , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Neoplasias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/imunologia , Cetuximab/efeitos adversos , Cetuximab/imunologia , Dessensibilização Imunológica/métodos , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Pacientes Ambulatoriais , Paclitaxel/efeitos adversos , Paclitaxel/imunologia , Portugal , Estudos Retrospectivos , Fatores de Risco , Testes Cutâneos/métodos , Taxoides/efeitos adversos , Taxoides/imunologia , Trastuzumab/efeitos adversos , Trastuzumab/imunologia , Adulto Jovem
7.
Zhonghua Zhong Liu Za Zhi ; 42(3): 170-179, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252195

RESUMO

Taxanes are cornerstones of cancer chemotherapy and can be used for the treatment of various tumors, including breast cancer. Taxane-associated peripheral neuropathy is a common adverse effect of taxanes, leading to discontinuation of drug therapy, affecting drug treatment outcomes, and severely affecting patients' quality of life. This consensus addresses and recommends the pathogenesis, clinical features, associated risk factors, diagnostic evaluation, prevention, and treatment of taxane-related peripheral neuropathy. It is hoped that this consensus will standardize the current management of taxane-related peripheral neuropathy in China and improve clinicians' understanding of taxane-related peripheral neuropathy, thereby improving patient outcomes and improving patient quality of life.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Síndromes Neurotóxicas/diagnóstico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Hidrocarbonetos Aromáticos com Pontes , China , Consenso , Humanos , Síndromes Neurotóxicas/etiologia , Guias de Prática Clínica como Assunto , Qualidade de Vida
8.
Medicine (Baltimore) ; 99(11): e19566, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176115

RESUMO

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients.Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy.A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22-44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P < .0001. Longer duration of chemotherapy (≥24 weeks) might also be associated with higher rate of amenorrhea (67.7%) compared to 43.4% in those who had shorter duration (<24 weeks), P = .031.The addition of taxanes to anthracycline-based chemotherapy increased the risk of amenorrhea. However, shorter duration of chemotherapy, even with taxanes, may lower such risk. Our study highlights the importance of fertility counseling to improve fertility preservation rates. Given the importance of taxanes, shorter regimens are associated with lower amenorrhea rates and should be preferred over longer ones.


Assuntos
Amenorreia/induzido quimicamente , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Preservação da Fertilidade , Taxoides/efeitos adversos , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Aconselhamento , Feminino , Humanos , Jordânia , Estadiamento de Neoplasias , Estudos Retrospectivos , Adulto Jovem
9.
Muscle Nerve ; 61(5): 587-594, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32052458

RESUMO

BACKGROUND: Our study aim was to evaluate neuromuscular ultrasound (NMUS) for the assessment of taxane chemotherapy-induced peripheral neuropathy (CIPN), the dose-limiting toxicity of this agent. METHODS: This cross-sectional study of breast cancer patients with taxane CIPN measured nerve cross-sectional area (CSA) by NMUS and compared with healthy historical controls. Correlations were determined between CSA and symptom scale, nerve conduction studies, and intraepidermal nerve fiber density (IENFD). RESULTS: A total of 20 participants reported moderate CIPN symptoms at a median of 3.8 months following the last taxane dose. Sural nerve CSA was 1.2 mm2 smaller than healthy controls (P ≤ .01). Older age and time since taxane were associated with smaller sural nerve CSA. For each 1 mm2 decrease in sural nerve CSA, distal IENFD decreased by 2.1 nerve/mm (R2 0.30; P = .04). CONCLUSIONS: These data support a sensory predominant taxane neuropathy or neuronopathy and warrant future research on longitudinal NMUS assessment of CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Nervo Mediano/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Nervo Sural/diagnóstico por imagem , Taxoides/efeitos adversos , Nervo Tibial/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Albuminas/efeitos adversos , Tornozelo , Neoplasias da Mama/patologia , Estudos Transversais , Docetaxel/efeitos adversos , Eletrodiagnóstico , Epiderme/patologia , Feminino , Antebraço , Humanos , Perna (Membro) , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Condução Nervosa , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Projetos Piloto , Estudos Prospectivos , Nervo Sural/fisiopatologia , Nervo Tibial/fisiopatologia , Punho
10.
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
11.
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
12.
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
13.
Cancer Chemother Pharmacol ; 85(3): 547-553, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31893292

RESUMO

PURPOSE: Cabazitaxel, used in patients with metastatic castration-resistant prostate cancer (mCRPC), is associated with adverse events which may require dose reductions or discontinuation of treatment. We investigated the potential association of single-nucleotide polymorphisms (SNPs) in genes encoding drug transporters and drug-metabolizing enzymes with cabazitaxel toxicity, overall survival (OS) and pharmacokinetics (PK). METHODS: A total of 128 cabazitaxel-treated mCRPC patients, of whom prospectively collected data on toxicity and OS were available and 24 mCRPC patients with available cabazitaxel PK measurements, were genotyped using genomic DNA obtained from EDTA blood. The SLCO1B1 (388A > G; *1B; rs2306283 and 521 T > C; *5; rs4149056 and haplotype SLCO1B1*15), SLCO1B3 (334 T > G; rs4149117), CYP3A4 (*22; rs35599367), CYP3A5 (*3; rs776746), ABCB1 (3435C > T; rs1045642), and TUBB1 (57 + 87A > C; rs463312) SNPs were tested for their association with clinical and PK parameters by univariate/multivariate logistic regression, log-rank test, or Kruskal-Wallis test. RESULTS: The SLCO1B1*15 haplotype was significantly associated with a lower incidence of leukopenia and neutropenia (p = 0.020 and p = 0.028, respectively). Patients harboring a homozygous variant for SLCO1B1*1B experienced higher rate ≥ grade 3 (p = 0.042). None of the SNPs were associated with pharmacokinetics or OS. CONCLUSIONS: In this study, SLCO1B1 (SLCO1B1*15 and SLCO1B1*1B) was associated with cabazitaxel-induced adverse events in mCRPC patients. As the associations were opposite to previous studies in other drugs and contradicted an underlying pharmacokinetic rationale, these findings are likely to be false-positive and would ideally be validated with even larger (pharmacokinetic) cohorts.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Idoso , Intervalo Livre de Doença , Haplótipos/genética , Humanos , Leucopenia/induzido quimicamente , Leucopenia/genética , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/genética , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
14.
Support Care Cancer ; 28(9): 4459-4466, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31925531

RESUMO

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side-effect of neurotoxic cancer treatment impacting on long-term quality of life. Symptoms include numbness, tingling, and pain, affecting the distal extremities. However, patients often report symptoms discrepant from the expected symmetrical distribution and the degree of concurrence with objective assessment remains ill-defined. This study aimed to investigate severity and symmetry of neuropathy symptoms to enable comparison of objective measures and patient report. METHODS: Forty-five taxane-treated patients (F = 43, 66 ± 1.5 years, 19 months post-treatment) completed bilateral neuropathy assessments via clinical examination, sensory nerve conduction studies (NCS), and patient questionnaires. The laterality index (LI) was calculated as a ratio of smaller to larger side-to-side differences. RESULTS: Neuropathy was reported by 89% of the cohort. On clinical examination, 83% had ≥ 2 abnormalities, with 38-35% having upper or lower limb sensory amplitudes below normative range. Thirty-five percent indicated side-to-side symptom asymmetry; however, there was no significant asymmetry evident on clinical examination (LI Asym = .60 ± .10, Sym = .76 ± .05, NS) and no difference in side-to-side NCS (median LI:Asym = .69 ± .06, Sym = .81 ± .04, NS; Sural LI:Asym = .80 ± .04, Sym = .81 ± .04, NS). Accordingly, there was no statistical association between patient-reported and objective assessment of side-to-side asymmetry, suggesting discordance between patient experience and objective assessment. Similarly, discrepancies in symptom severity between hands and feet were reported by 32% of the cohort. However, patients reporting differences in symptom severity between the hands and feet were just as likely to present with comparable assessments as to demonstrate objective discrepancies. CONCLUSIONS: Discrepancies may exist between the patient experience of CIPN and objective assessments. Understanding these discrepancies may help to elucidate underlying mechanisms and better inform treatment strategies.


Assuntos
Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxoides/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Oncol Pharm Pract ; 26(6): 1421-1428, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31937190

RESUMO

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is a common and bothersome toxicity. This study aimed to determine the incidence and severity of TIPN in patients with breast cancer and to investigate the relationship between TIPN and quality of life. METHODS: A total of 82 breast cancer patients with TIPN symptoms were included in this study. The criteria of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) were used to evaluate grading of sensory neuropathy and quality of life, respectively. Analysis of the data was done by IBM SPSS statistics version 23. RESULTS: A total of 346 patients received taxane-based chemotherapy and 82 patients (23.7%) experience TIPN. The mean (SD) global health status/quality of life, physical functioning, role functioning, and pain subscales were 60.63 (5.26), 80.64 (9.05), 81.77 (10.41), and 43.88 (11.27), respectively. There were significant negative correlations between global health status/quality of life, physical functioning, and role functioning subscales with the grade of neuropathy (r = -0.33, -0.80, and -0.61, respectively) and positive correlation between pain subscale and the grade of neuropathy (r = 0.70). CONCLUSION: This study shows a clear association between TIPN and worsened quality of life. These findings emphasize on detecting and management of TIPN in an effort to improve the quality of life of breast cancer patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxoides/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Taxoides/administração & dosagem
16.
Gynecol Oncol ; 156(3): 530-534, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31937450

RESUMO

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Adulto Jovem
17.
Gynecol Oncol ; 156(3): 695-700, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31928805

RESUMO

OBJECTIVES: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. Our goal was to evaluate if sarcopenia was associated with worse survival outcomes and chemotoxicity in EOC patients undergoing primary platinum and taxane-based chemotherapy. METHODS: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic - version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and unpaired t-tests were used to compare the means by groups. RESULTS: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). No difference in frequency of dose reduction, dose delay, hospital admissions, changes in regimen, blood transfusion, or toxicity was noted. There was no difference in distribution of toxicity grade. CONCLUSION: Sarcopenia was not associated with worse survival outcomes or chemotoxcity in EOC patients receiving first-line platinum and taxane-based chemotherapy in this cohort. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival, performance status, and quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Sarcopenia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Prognóstico , Intervalo Livre de Progressão , Sarcopenia/etiologia , Sarcopenia/fisiopatologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Estados Unidos/epidemiologia
18.
Sci Rep ; 10(1): 530, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953463

RESUMO

The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69-3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07-3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62-0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54-0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Segurança , Solventes/química , Taxoides/química , Taxoides/farmacologia , Paclitaxel Ligado a Albumina/efeitos adversos , Paclitaxel Ligado a Albumina/uso terapêutico , Humanos , Metástase Neoplásica , Taxoides/efeitos adversos , Taxoides/uso terapêutico
19.
J Cancer Res Clin Oncol ; 146(2): 449-455, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838576

RESUMO

PURPOSE: Outcomes of multiply relapsed, refractory germ-cell tumour (GCT) patients remain poor with an overall survival (OS) of a few months only. Thus, new therapeutic advances are urgently needed. Cabazitaxel has shown preclinical activity in platinum-resistant GCT models. Here, we report the first clinical case series of cabazitaxel treatment for platinum-refractory GCT. METHODS: Data of multiply relapsed GCT patients receiving single-agent cabazitaxel were retrospectively analysed. Endpoints included 12-week progression-free survival (PFS) rate, disease control rate, tumour marker responses, median PFS and OS, and toxicity. RESULTS: Cabazitaxel showed limited activity in 13 heavily pre-treated GCT patients. After a median follow-up of 23 weeks (IQR 29), 69% of patients were deceased. A median of 2 cycles of cabazitaxel (range 1-7) were applied. The 12-week PFS rate was 31%. Median PFS and OS were 7 and 23 weeks, respectively. Two patients achieved objective responses (15%), three patients (23%) achieved a tumour marker decline ≥ 50%, and the disease control rate was 39%. Cabazitaxel was well tolerated. CTCAE° III-IV haemato-toxicity was most common (54%), and dose reductions were scarce (15%). CONCLUSION: In this case series, cabazitaxel showed limited activity in heavily pre-treated GCT patients. Two-phase II studies are underway (NCT02115165, NCT02478502) prospectively assessing cabazitaxel in multiply relapsed GCTs.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Neoplasias Testiculares/patologia
20.
Breast ; 49: 187-193, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865282

RESUMO

BACKGROUND: Randomized controlled trials (RCT) of scalp cooling (SC) to prevent chemotherapy induced alopecia (CIA) did not evaluate its effect on hair regrowth (HR) and was conducted in a predominantly taxane (T) treated population. We conducted an RCT of SC in a setting of anthracycline (A) and taxane chemotherapy (CT) and assessed its effect on CIA and HR. METHODS: Non-metastatic breast cancer women undergoing (neo) adjuvant CT were randomized to receive SC using the Paxman scalp cooling system during every cycle of CT, or no SC. The primary end point (PEP) was successful hair preservation (HP) assessed clinically and by review of photographs after CT. HR was assessed at 6 and 12 weeks. RESULTS: 51 patients were randomized to SC (34) or control arm (17) in a 2:1 ratio. Twenty-five (49%) patients received A followed by T and the two arms were balanced with respect to this factor. HP rate was significantly higher in SC arm compared to control arm (56.3% vs 0%, P = 0.000004). HR was higher in SC arm compared to control at 6 weeks (89% vs 12%; P < 0.001) and 12 weeks (100% vs 59%, P = 0.0003). Loss of hair at PEP evaluation, which was a quality of life measure, was significantly lower in SC versus control arm (45% vs 82%, P = 0.016). There were no grade 3-4 cold related adverse effects. CONCLUSIONS: Women with breast cancer receiving A or T chemotherapy receiving SC were significantly more likely to have less than 50% hair loss after CT, superior hair regrowth and improvement in patient reported outcomes, with acceptable tolerance. It merits wider usage.


Assuntos
Alopecia/prevenção & controle , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Crioterapia/métodos , Taxoides/efeitos adversos , Adulto , Alopecia/induzido quimicamente , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Couro Cabeludo , Resultado do Tratamento , Adulto Jovem
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