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1.
Bull Cancer ; 2020 Mar 31.
Artigo em Francês | MEDLINE | ID: mdl-32245605

RESUMO

INTRODUCTION: Medical oncology bad news consultation is a particularly stressful situation for both the patient and the physician. High-fidelity simulation is a learning option that has never been evaluated in France in this field. MATERIALS AND METHODS: This is a feedback from simulated announcement consultations carried out from January 2018 to May 2019. Residents from the medical oncology and radiotherapy departments performed high-fidelity simulations at the announcement consultation with an announcement nurse, a psychologist, a certified coach and an oncologist. A competency assessment was completed in pre-test, immediate post-test and after 5 months. RESULTS: Fourteen of the 16 eligible interns participated. The pre-test competency assessment showed that interns over 5 semesters reported being more comfortable at the consultation (P=0.04) and thought they were clearly explaining the disease (P=0.03). However, all residents, regardless of the semester, felt stressed before a consultation. The evolution of parameters skills after the simulation was positive for all criteria, particularly for adaptation to patient reactions, use of appropriate vocabulary and reduction of stress (P<0.05). This evolution was independent of the gender, curriculum, semester, or previous completion of a medical oncology internship. More than 80% of the students were ready to repeat this type of training. CONCLUSION: This training demonstrates the value of simulation training for medical oncology advertising consultation.

2.
J Geriatr Oncol ; 10(1): 159-163, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30037767

RESUMO

INTRODUCTION: Management of glioblastoma, with a very poor prognosis, remains a challenge in older patients because of coexisting comorbidities and the increased risk of toxic treatment effects. The use of screening tools to identify vulnerable patients is essential. This study was performed to establish whether the G8 scale can be used for screening older patients with glioblastoma. METHODS: We retrospectively reviewed the files of patients assessed by the G8 scale and diagnosed with glioblastoma at a single center from January 2010 to July 2017. Patients aged 65 years or older were classified into three groups (more efficiently than two groups) according to their G8 score to identify those with a poor prognosis: high score group, G8 score 14.5-17; intermediate score group, G8 score 10.5-14; and low score group, G8 score < 10.5. RESULTS: Of 89 patients, 19% were classified into the high score group, 43% into the intermediate score group, and 38% into the low score group. Median overall survival was four months in the low score group, 15 months in the intermediate score group, and 42 months in the high score group (p < .0001). On multivariate analysis, G8 score was a significant independent predictor of overall survival (hazard ratio: 55.46; 99.5% confidence interval: 13.42-229.13; p < .0001). CONCLUSIONS: Here, we highlighted the possibility of using the G8 score, with possibly three cut-offs, in the management of older patients with glioblastoma and determined the prognostic role of this quick and easy screening tool.

3.
Clin Breast Cancer ; 18(6): e1311-e1321, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30098917

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. MATERIALS AND METHODS: We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. RESULTS: The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (-0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. CONCLUSION: ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/sangue , Neoplasias da Mama/sangue , Terapia Neoadjuvante/mortalidade , Fator A de Crescimento do Endotélio Vascular/sangue , Ácido Zoledrônico/uso terapêutico , Adulto , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/sangue , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
4.
Support Care Cancer ; 26(3): 861-868, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28948392

RESUMO

PURPOSE: We investigated the impact of body composition on outcomes of patients with early breast cancer. Skeletal muscle mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and muscle fat infiltration or inter-muscular adipose tissue areas (IMAT), obtained by computed tomography (CT), were assessed. METHODS: A total of 119 female patients who had breast cancer were included in this retrospective study. The total skeletal muscle and fat tissue areas were evaluated in two adjacent axial slices obtained at the third lumbar vertebra by CT used for disease staging. The women were assigned to either a sarcopenia or non-sarcopenia group based on their skeletal muscle index (cut-off 41.0 cm2/m2). They also were classified into high and low VAT/SAT ratio groups and assigned to either the high or low IMAT index group. The association of the body composition parameters and prognosis was statistically analyzed. RESULTS: Among the 119 evaluable patients, 58 were sarcopenic (48.8%), 55 (46.2%) had a high VAT/SAT ratio, and 62 (52.1%) had a high IMAT index. Median follow-up was 52.4 months. Multivariate analysis revealed sarcopenia and IMAT index as independent prognostic factors for disease-free survival (p = 0.02 and p = 0.04, respectively) and overall survival (p = 0.05 and p = 0.02, respectively). BMI was not significantly associated with disease-free survival, but a trend was observed (p = 0.09). CONCLUSIONS: Sarcopenia and IMAT index are independent prognostic factors in early breast cancer; therefore, assessing body composition could be a simple and useful approach to integrate into patient management.


Assuntos
Composição Corporal/fisiologia , Neoplasias da Mama/complicações , Sarcopenia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
5.
Clin Breast Cancer ; 18(1): e41-e47, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28666812

RESUMO

PURPOSE: Single-agent oral chemotherapy is widely used in patients with bone metastases without visceral involvement, especially in hormone receptor-positive metastatic breast cancer (mBC). However, this option has been poorly evaluated in clinical trials. METHODS: Eligible patients had mBC with predominantly bone but not visceral metastases, were receiving bisphosphonate therapy, and had previously received endocrine therapy (any setting) but not chemotherapy for mBC. Patients received oral vinorelbine 60 mg/m2 on days 1, 8, 15, and 22 every 4 weeks (escalating to 80 mg/m2 from cycle 2 in the absence of grade 3/4 toxicity) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included clinical benefit rate (complete/partial response or ≥24 weeks' stable disease), overall survival, and safety. RESULTS: Seventy patients were treated for a median of 6 cycles (range 1-18). Most (73%) continued treatment until disease progression. After 43 months' median follow-up, median PFS was 8.2 months (95% confidence interval [CI], 5.5-9.8). The clinical benefit rate was 56% (95% CI, 43%-68%). Median overall survival was 35.2 months (95% CI, 26.8-47.1). The most common grade 3/4 adverse event was neutropenia (38% of patients); febrile neutropenia was absent. The most common grade 1/2 adverse events were bone pain, fatigue, and gastrointestinal toxicities. Alopecia was infrequent. CONCLUSIONS: In patients with hormone receptor-positive mBC, bone disease, and prior endocrine therapy, first-line oral vinorelbine chemotherapy demonstrated long PFS and good tolerability. In this setting, it could be considered as an active oral alternative to intravenous chemotherapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Vinorelbina/uso terapêutico , Administração Oral , Adulto , Idoso , Neoplasias Ósseas/secundário , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Progressão da Doença , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
6.
Eur Urol ; 73(5): 696-703, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29074061

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC. OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance. RESULTS AND LIMITATIONS: Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups. CONCLUSIONS: Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients. PATIENT SUMMARY: Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Idoso , Idoso de 80 Anos ou mais , Bélgica , Intervalos de Confiança , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , França , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
7.
BMC Cancer ; 17(1): 901, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282011

RESUMO

BACKGROUND: Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC. METHODS: Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6-9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and "environmental" risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with "environmental" risk factors. RESULTS: No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29-8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10-3.39], p = 0.0257) in the "never alcohol consumption subgroup" (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70-10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48-4.23], p = 0.0006 and OR = 2.99[1.63-5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63-6.96], p = 0.0010). CONCLUSIONS: Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup. TRIAL REGISTRATION: Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008-0144.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Fatores de Risco
8.
BMC Cancer ; 17(1): 662, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28954632

RESUMO

BACKGROUND: The objective of this study was to compare the efficacy of biomarkers in assessing the risk of breast cancer recurrence in patients with node-negative or micrometastatic grade II breast cancer. Specifically, we compared risk assessments based on the St. Gallen clinicopathological criteria, Ki67 expression and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) expression. METHODS: This retrospective study included 347 patients with breast cancer followed at Limoges University Hospital. The optimal cut-off for high Ki67 expression (Ki67hi) was established as 20%. The threshold for uPA and PAI-1 positivity was 3 ng/mg and 14 ng/mg, respectively. RESULTS: Ki67 expression was lower in uPA/PAI-1-negative than in uPA/PAI-1-positive tumours (227 tumours; P = 0.04). The addition of Ki67 status to the St. Gallen criteria resulted in a 28% increase in the rate of identification of high-risk tumours with a potential indication for chemotherapy (P < 0.001). When considering uPA/PAI-1 levels together with the St Gallen criteria (including Ki67 expression), the number of cases identified as having a high recurrence risk with a potential indication for adjuvant chemotherapy increased by 20% (P < 0.001). Adjuvant chemotherapy was 9% less likely to be recommended by a multidisciplinary board when using the current criteria compared with using a combination of the St. Gallen criteria and Ki67 and uPA/PAI-1 status (P = 0.03). CONCLUSIONS: Taken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Fatores de Risco
9.
Pharmacol Res ; 121: 138-144, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28473246

RESUMO

INTRODUCTION: Therapeutic drug monitoring (TDM) of everolimus is not performed in oncology and no trough level (C0) target has been yet defined. The aim of this study was to determine everolimus C0 target for toxicity and efficacy. MATERIALS AND METHODS: Clinical, biological and radiologic data from 54 patients were collected. Toxicity event was defined by termination, temporary interruption and/or dose reduction of everolimus while efficacy was defined as progression-free survival. C0 values were dichotomized by ROC curve analysis and the association between exposure and outcome was determined using Cox models for repeated events (toxicity) or Cox model censured at the first event (progression free survival). RESULTS: Among the 42 patients (77.8%) with breast cancer, 10 (18.5%) kidney cancer and 2 (3.7%) neuroendocrine cancer, adverse events were reported in 75.9% of the patients (everolimus termination in 25.9% patients). C0 everolimus higher than 26.3ng/mL (Sen=0.38,Spe=0.88) were associated with a 4-fold increased risk of toxicity (HR=4.12, IC95%=[1.48-11.5], p=0.0067) whereas C0 lower than 11.9ng/mL were associated with a 3-fold increased risk of progression (HR=3.2, IC95%=[1.33-7.81],p=0.001). DISCUSSION: Further studies are required to evaluate the everolimus C0 threshold proposed for toxicity (26.3ng/mL) and for progression (11.9ng/mL) especially with a large number of patients and more homogeneous types of cancer. However, these results are in favour of TDM for everolimus in oncology.


Assuntos
Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Monitoramento de Medicamentos , Everolimo/sangue , Everolimo/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Everolimo/efeitos adversos , Everolimo/farmacologia , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia
10.
Clin Breast Cancer ; 17(2): 91-99.e1, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27756583

RESUMO

BACKGROUND: The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). PATIENTS AND METHODS: In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). RESULTS: The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. CONCLUSION: All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Receptor ErbB-2/metabolismo , Vimblastina/análogos & derivados , Administração Intravenosa , Administração Oral , Adulto , Idoso , Alopecia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Fadiga/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Qualidade de Vida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina
11.
J Geriatr Oncol ; 7(3): 187-94, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27085302

RESUMO

OBJECTIVES: Effectiveness of bevacizumab for metastatic colorectal cancer in elderly patients has been investigated in observational studies, mainly associated with oxaliplatin-based regimens. Here, using the ETNA cohort in which the majority of patients received bevacizumab+FOLFIRI, the effectiveness of this combination in elderly patients is explored. MATERIALS AND METHODS: Patients initiating first-line therapy with bevacizumab between January 2006 and December 2007 were identified in 28 French centres and followed for 24months. Vital status was collected over 36months. In the present analysis those who received FOLFIRI were retained (85% of those included), and patients were stratified by age (<70/≥70years). The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS), and Cox models were used to assess the independent effect of age on survival outcomes. RESULTS: Among the 351 patients who received bevacizumab+FOLFIRI, 33.9% were aged ≥70years, 66.1% <70years. Respectively 15.1% and 9.5% of patients had ECOG-PS ≥2; 49.6% and 40.1% used 'stop-and-go' treatment scheduling; and 56.3% and 44.4% experienced grade 3/4 adverse events. Overall response rate was 58.8% and 62.5%. Median [95% confidence interval, CI] OS was respectively 24.1 [20.4; 26.2] and 28.5 [25.0; 31.0] months; age≥70years and ECOG-PS≥2 were significantly associated with death. Median PFS [95% CI] was respectively 10.9 [9.4; 12.6] and 9.8 [9.2; 11.2] months; hepatic metastases was associated with progression, and age ≥70years was associated with progression after 14months of follow-up but not before. CONCLUSIONS: The present study adds to the literature on the safe and beneficial effect of bevacizumab in the elderly receiving FOLFIRI regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/uso terapêutico , Estudos de Coortes , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Taxa de Sobrevida
12.
J Transl Med ; 14: 10, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26791256

RESUMO

BACKGROUND: Colorectal cancer (CRC) remains a major public concern. While conventional chemotherapeutic regimens have proved useful against advanced/metastatic diseases, progresses are to be made to effectively cure the large portion of patients not benefiting from these treatments. One direction to improve response rates is to develop chemosensitivity and resistance assays (CSRAs) efficiently assisting clinicians in treatment selection process, an already long preoccupation of oncologists and researchers. Several methods have been described to this day, none achieving yet sufficient reliability for recommended use in the clinical routine. METHODS: We led a pilot study on 19 metastatic CRC patients evaluating capacity of the Oncogramme, a standardized process using tumor ex vivo models, to provide chemosensitivity profiles and predict clinical outcome of patients receiving standard CRC chemotherapeutics. Oncogramme responses were categorized according to the method of percentiles to assess sensitivity, specificity and concordance. RESULTS: We report from a primary analysis a success rate of 97.4 %, a very good sensitivity (84.6 %), a below-average specificity (33.3 %), along with a global agreement of 63.6 % and a concordance between Oncogramme results and patients' responses (Kappa coefficient) of 0.193. A supplementary analysis, focusing on CRC patients with no treatment switch over a longer time course, demonstrated improvement in specificity and concordance. CONCLUSIONS: Results establish feasibility and usefulness of the Oncogramme, prelude to a larger-scale trial. Advantages and drawbacks of the procedure are discussed, as well as the place of CSRAs within the future arsenal of methods available to clinicians to individualize treatments and improve patient prognosis. TRIAL REGISTRATION: ClinicalTrials.gov database, registration number: NCT02305368.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Projetos Piloto , Resultado do Tratamento
13.
Eur J Phys Rehabil Med ; 52(2): 223-32, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25986222

RESUMO

BACKGROUND: Breast cancer chemotherapy is associated with a decline in measured cardiorespiratory fitness and increased fatigue. Physical activity has emerged as a feasible intervention to limit these side effects. Quantitative evaluation is necessary to propose a better-adapted physical activity and to evaluate efficacy. AIM: We undertook a prospective study to assess the effects of a home-based adapted physical activity (APA) program on aerobic capacity, strength, and fatigue in women treated with adjuvant or neoadjuvant chemotherapy for breast cancer versus usual care. DESIGN: This was an open two-arm, randomized controlled trial. SETTING: Study included outpatient groups in the Department of Physiology and Medical Oncology of a hospital in France. POPULATION: Forty-four patients treated with adjuvant or neoadjuvant chemotherapy for breast cancer. METHODS: Patients were randomly assigned to a control group or an APA group. Intervention consisted of a 3-week, home-based, supervised, combined APA program (endurance and resistance training) during 27 weeks. The primary endpoint was cardiopulmonary function assessed by maximal peak oxygen consumption (VO2peak). Secondary endpoints included a 6-minute Walking Test (6MWT), and assessment of muscular strength, fatigue, quality of life, physical activity level, and anxiety/depression. RESULTS: At 27 weeks, VO2peak increased by 1.83±0.68 ml.min-1.kg-1 in the APA group (P=0.009) and decreased by 1.31±0.65 mL.min-1.kg-1 in the control group (P=0.046). The difference between the two groups was not significant (2.26±1.53 mL.min-1.kg-1, P=0.140) in intention-to-treat analysis, but it was significant in per protocol analysis (3.49±1.64 mL.min-1.kg-1, P=0.049). At 27 and 54 weeks, no significant differences were observed between the two groups for the cardiopulmonary exercise test, 6MWT, quadriceps strength, or quality of life. CONCLUSIONS: In breast cancer patients, a home-based supervised program during chemotherapy and radiotherapy treatment may be safe, feasible and increase VO2peak. In this study, heavy evaluation tests explain patient's non-adherence and do not permit to obtain statistically significant results between APA and control groups. CLINICAL REHABILITATION IMPACT: Aerobic home-based adapted physical activity is beneficial on aerobic capacity.


Assuntos
Neoplasias da Mama/reabilitação , Terapia por Exercício , Tolerância ao Exercício/fisiologia , Fadiga/prevenção & controle , Serviços de Assistência Domiciliar , Consumo de Oxigênio/fisiologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Terapia Neoadjuvante , Cooperação do Paciente , Estudos Prospectivos , Qualidade de Vida
14.
Target Oncol ; 11(1): 83-92, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26298481

RESUMO

PURPOSE: Resection of metastases after chemotherapy improves survival outcomes of patients with initially inoperable metastatic colorectal cancer (mCRC), yet little data is available for those treated in the first-line setting with bevacizumab plus irinotecan. To provide data on this, the present study described the subgroup of the ETNA cohort who underwent metastases surgery. METHODS: The population of operated patients was described according to metastatic site (exclusively hepatic, non-exclusively hepatic, and non-hepatic). Factors associated with overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox analysis. RESULTS: A total of 76 patients (21.1 % of the ETNA cohort) underwent metastases resection: 50 % male, median age 61.9 years, 85.5 % ECOG ≤ 1, and median duration of bevacizumab use 7.2 months. No surgery-related deaths were observed and 30.6 % of patients had at least one post-operative complication, mainly infections (11.8 % of resections), bleeding complications (3.5 %), or delayed wound healing (2.4 %). Complete remission was higher for those with exclusively hepatic metastases (22/32, 68.8 %) than those with non-exclusively hepatic metastases (12/24, 50.0 %), or non-hepatic metastases (12/20, 60.0 %). Among operated patients, 52.6 % had died after 5 years of follow-up. In multivariable analysis at 2 years of follow-up, death (HR 0.09 [95 % CI 0.02-0.35]) and progression (HR 0.35 [95 % CI 0.23-0.56]) were less likely for patients with complete remission (CR) after surgery R0-R1 or radiofrequency ablation (RFA) [CR RFA] compared with those who were not resected or with R2 resection. CONCLUSION: In real-life practice, bevacizumab with irinotecan in first-line therapy for mCRC allows secondary resection of metastases and survival is more favourable in those with complete remission (R0-R1/CR RFA).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Metastasectomia , Idoso , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Estudos de Coortes , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
15.
Lancet Oncol ; 16(15): 1493-1505, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26474518

RESUMO

BACKGROUND: The combination of an anti-VEGF or an anti-EGFR-targeted monoclonal antibody with chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. However, combining both anti-VEGF and anti-EGFR antibodies with chemotherapy in first-line treatment resulted in adverse outcomes. We assessed whether the combination of erlotinib, an EGFR tyrosine kinase inhibitor, with bevacizumab could increase the efficacy of maintenance therapy in patients with unresectable metastatic colorectal cancer. METHODS: This randomised, open-label, phase 3 study was undertaken in 49 centres in France, Austria, and Canada. Eligible patients were aged 18-80 years with histologically confirmed, unresectable metastatic colorectal cancer, WHO performance status 0-2, had received no previous therapy for metastatic disease, and had adequate organ function. Patients without disease progression after bevacizumab-based induction therapy were randomly assigned (1:1) by a minimisation technique to bevacizumab (7·5 mg/kg every 3 weeks) or bevacizumab plus erlotinib (150 mg once daily) as maintenance therapy until progression. All patients were stratified by centre, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy analysed by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00265824. FINDINGS: Between Jan 1, 2007, and Oct 13, 2011, 700 eligible patients were enrolled; following induction treatment, patients without disease progression were randomly assigned to bevacizumab (n=228) or bevacizumab plus erlotinib (n=224). At the final analysis, median follow-up was 51·0 months (IQR 36·0-60·0) in the bevacizumab group and 48·3 months (31·5-61·0) in the bevacizumab plus erlotinib group. In the primary analysis (after 231 progression-free survival events), median progression-free survival from randomisation was 5·1 months (95% CI 4·1-5·9) in the bevacizumab plus erlotinib group compared with 6·0 months (4·6-7·9) in the bevacizumab group (stratified hazard ratio [HR] 0·79 [95% CI 0·60-1·06]; p=0·11; unstratified HR 0·76 [0·59-0·99]; p=0·043). In the final analysis, median progression-free survival from randomisation was 5·4 months (95% CI 4·3-6·2) in the bevacizumab plus erlotinib group compared with 4·9 months (4·1-5·7) in the bevacizumab group (stratified HR 0·81 [95% CI 0·66-1·01], p=0·059; unstratified HR 0·78 [0·68-0·96], p=0·019). At the final analysis, median overall survival from maintenance was 24·9 months (95% CI 21·4-28·9) in the bevacizumab plus erlotinib group and 22·1 months (19·6-26·7) in the bevacizumab group (stratified HR 0·79 [95% CI 0·63-0·99], p=0·036; unstratified HR 0·79 [0·64-0·98], p=0·035). The most frequent grade 3-4 adverse events were skin rash (47 [21%] of 220 patients in the bevacizumab plus erlotinib group vs none of 224 patients in the bevacizumab alone group), diarrhoea (21 [10%] vs two [<1%]), and asthenia (12 [5%] vs two [<1%]). INTERPRETATION: Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy. FUNDING: GERCOR and F Hoffmann-La Roche.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Cloridrato de Erlotinib/administração & dosagem , Quimioterapia de Manutenção , Idoso , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Oncotarget ; 6(14): 12796-808, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25918250

RESUMO

To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Receptor ErbB-2/antagonistas & inibidores , Terapia de Salvação/métodos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
17.
BJU Int ; 115(1): 65-73, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24180479

RESUMO

OBJECTIVE: To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain. PATIENTS AND METHODS: This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis. RESULTS: The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose intensity of treatments, efficacy and safety. CONCLUSION: In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Metástase Neoplásica , Cuidados Paliativos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina
18.
Bull Cancer ; 101(7-8): 741-7, 2014.
Artigo em Francês | MEDLINE | ID: mdl-25025796

RESUMO

Available data on appropriate follow-up in endometrial cancer highlight the need of well-conducted studies. Most recurrences tend to occur within three years and involve symptoms. Routine tests are not advocated without symptoms. In case of suspicious recurrence, TEP/CT seems to be the most sensitive and specific method. There is limited evidence to decide whether follow-up schedules with multiple visits result in survival benefits. An appropriate follow-up should be discussed based upon the risk of recurrence. Counselling on the potential symptoms of recurrence should be a major aim.


Assuntos
Neoplasias do Endométrio/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Vigilância da População/métodos , Antígeno Ca-125/análise , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/mortalidade , Segunda Neoplasia Primária/diagnóstico , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , Prognóstico , Avaliação de Sintomas , Esfregaço Vaginal
19.
Anticancer Res ; 34(3): 1213-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24596362

RESUMO

BACKGROUND: The urokinase-type plasminogen activator (UPA) and its main inhibitor plasminogen activator inhibitor-1 (PAI-1) are involved in tumor interactions with the microenvironment. The UPA/PAI-1 content in tumor tissue can be used to identify populations at low-or high-risk of recurrence of breast cancer, even without other standard prognostic markers. MATERIALS AND METHODS: The purpose of the present study was to compare adjuvant chemotherapy decisions made by a multi-disciplinary board for 163 node-negative breast cancer cases, based on clinicopathological (CP) and UPA/PAI-1 risk assessment. RESULTS: The UPA/PAI-1 levels identified 37% of the population as being at low risk. Adjuvant chemotherapy indication was spared in high-CP risk in 17%, but maintained in low-CP risk in 33%. CONCLUSION: The use of UPA/PAI-1 data did not consistently result in a decrease of adjuvant chemotherapy. This study highlighted the difficulties encountered in a local multi-disciplinary board in determining appropriate roles and weights of new prognostic markers (UPA/PAI-1 was not routinely employed in France) when no data are available for assessing their prognostic and predictive power compared to other prognostic factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tomada de Decisões , Linfonodos/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Linfonodos/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos
20.
Anticancer Res ; 33(6): 2657-64, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23749924

RESUMO

UNLABELLED: Chemotherapy plus trastuzumab is the standard first-line treatment for Human Epidermal Receptor 2-positive (HER2-positive) metastatic breast cancer. The aim of this international phase II trial was to determine the efficacy and safety profile of an oral chemotherapy doublet, oral vinorelbine plus capecitabine, and trastuzumab in this setting. PATIENTS AND METHODS: In this single-arm, multicenter, open-label phase II study, in the first-line metastatic setting, patients received 3-weekly cycles of oral vinorelbine at 80 mg/m(2) (first cycle dose 60 mg/m(2)) day 1 and day 8, plus capecitabine at 1000 (750 if ≥ 65 years) mg/m(2) twice daily on days 1-14, plus trastuzumab at 4 mg/kg intravenously (i.v.) on day 1 (loading dose) then 2 mg/kg i.v. weekly thereafter. Treatment was continued until progression or unacceptable toxicity. RESULTS: Fifty patients with a median age of 53.5 years were enrolled. Most (82%) had visceral involvement and 34% had more than two metastatic sites. The objective response rate (RECIST 1.0) in 44 evaluable patients was 77% [95% Confidence Interval (CI)=62-89%], including complete response in 21%. The clinical benefit rate (response or stable disease for ≥ 6 months) was 93% [95% CI=81-99%]. Median duration of response was 13.3 [95% CI=9.8-15.7] months, median progression-free survival was 12.8 [95% CI=10.8-16.9] months and median overall survival was 47.0 [95% CI=30.5-64.3] months. Median number of cycles was 10 (range 1-81). The majority of patients (72%) received more than 18 weeks and 32% more than 48 weeks of treatment. The most frequent treatment-related grade 3/4 adverse events were neutropenia (71%), hand-foot syndrome (20%) and diarrhea (16%). A low-rate of grade 2 alopecia was observed (14%). CONCLUSION: The triple combination of oral vinorelbine, capecitabine and trastuzumab is highly active in terms of response rate, progression-free survival and overall survival, with a manageable toxicity profile.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2/metabolismo , Taxa de Sobrevida , Trastuzumab , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina
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