Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
2.
Gynecol Oncol ; 171: 106-113, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36868112

RESUMO

RATIONALE: Homologous recombination deficiency (HRD), defined as BRCA1/2 mutation (BRCAmut) or high genomic instability, is used to identify ovarian cancer (OC) patients most likely to benefit from PARP inhibitors. While these tests are useful, they are imperfect. Another approach is to measure the capacity of tumor cells to form RAD51 foci in the presence of DNA damage using an immunofluorescence assay (IF). We aimed to describe for the first time this assay in OC and correlate it to platinum response and BRCAmut. METHODS: Tumor samples were prospectively collected from the randomized CHIVA trial of neoadjuvant platinum +/- nintedanib. IF for RAD51, GMN and gH2AX was performed on FFPE blocks. Tumors were considered RAD51-low if ≤10% of GMN-positive tumor cells had ≥5 RAD51 foci. BRCAmut were identified by NGS. RESULTS: 155 samples were available. RAD51 assay was contributive for 92% of samples and NGS available for 77%. gH2AX foci confirmed the presence of significant basal DNA damage. 54% of samples were considered HRD by RAD51 and presented higher overall response rates to neoadjuvant platinum (P = 0.04) and longer progression-free survival (P = 0.02). In addition, 67% of BRCAmut were HRD by RAD51. Among BRCAmut, RAD51-high tumors seem to harbor poorer response to chemotherapy (P = 0.02). CONCLUSIONS: We evaluated a functional assay of HR competency. OC demonstrate high levels of DNA damage, yet 54% fail to form RAD51 foci. These RAD51-low OC tend to be more sensitive to neoadjuvant platinum. The RAD51 assay also identified a subset of RAD51-high BRCAmut tumors with unexpected poor platinum response.


Assuntos
Neoplasias Ovarianas , Platina , Humanos , Feminino , Platina/uso terapêutico , Recombinação Homóloga , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Dano ao DNA , Proteína BRCA1/genética , Rad51 Recombinase/genética
3.
Gynecol Oncol ; 170: 186-194, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36706645

RESUMO

AIM: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer. METHODS: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS. RESULTS: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo. CONCLUSIONS: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS). CLINICALTRIALS: govregistration: NCT01583322.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/patologia , Terapia Neoadjuvante , Quimioterapia Adjuvante , Carboplatina , Paclitaxel , Procedimentos Cirúrgicos de Citorredução , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias
4.
Bull Cancer ; 110(2): 184-192, 2023 Feb.
Artigo em Francês | MEDLINE | ID: mdl-36411129

RESUMO

INTRODUCTION: Oncological at home-treatment improves patient quality of life and autonomy but requires close watchfulness of adverse events and compliance to treatment. For nearly ten years, pharmaceutical consultations for home-based anticancer oral therapies patients are proposed on medical request in Avignon-Provence Cancer Institute (ICAP). Organizational changes led us to modify this management by integrating dedicated nurses to create an Oral Therapy Unit (OTU). MATERIALS ET METHODS: Needs and expectations assessment questionnaires were proposed to healthcare professionals and patients treated by oral therapies. The analysis of these questionnaires allows to set up an OTU, integrating a dedicated nurse, adapted to the expectations of patients and healthcare professionals. About 8 months later, a new evaluation was carried out to assess the impact of this new support for patient care and health professionals' organization. RESULTS: The results of the studies carried out before OTU implementation highlight the importance of multi-professional support for patients from the start of treatment and during the follow-up. With the new OTU pathway, professionals expect a patient course improvement (94%), a better compliance (88%), a therapeutic accidents reduction (81%) and an improvement in the patient-caregiver relationship (69%). Regarding the organization, 56% of them are expecting to save medical and pharmaceutical time. CONCLUSION: The OTU creation in our institution and these new multi-professionals' teams' management of patients has obtained a favourable opinion from healthcare professionals and patient satisfaction.


Assuntos
Pessoal de Saúde , Qualidade de Vida , Humanos , Avaliação das Necessidades , Cuidadores , Preparações Farmacêuticas
5.
Eur J Nucl Med Mol Imaging ; 48(6): 1998-2008, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33221969

RESUMO

BACKGROUND: This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery. MATERIALS AND METHODS: Central review was performed by two readers blinded to the received treatment and to the patients' outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG). RESULTS: Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease < 0.25 cm/0.25-2.5 cm/> 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle. CONCLUSION: 18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival. TRIAL REGISTRATION: NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Ovarianas , Feminino , Humanos , Indóis , Terapia Neoadjuvante , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Cirurgia de Second-Look , Resultado do Tratamento , Carga Tumoral
6.
Support Care Cancer ; 29(7): 3735-3742, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33205324

RESUMO

BACKGROUND: Metastatic breast cancer (MBC) patients experience long survival and report poorer quality of life than localized breast cancer patients. Comprehensive supportive care (CSC) has been shown to improve the quality of life (QoL) of MBC. The respective part of each support care has not been fully examined, and little is known about whether meeting patients' needs is accompanied by decreased unscheduled hospital care (UHC). METHODS: This prospective monocentric study included women who started a new treatment line for MBC between January 2018 and December 2018. The endpoints were factors associated with UHC and QoL (SF36) at month 12. RESULTS: 100 patients were offered CSC, 78 were included (21 refusals, 1 no MBC). CSC was provided to 60 patients: pain (43%), psychological (37%), kinesitherapy (30%), social assistance (22%), esthetic (18%), nutrition (18%), massage (13%), and none (10%). CSC rate was not statistically different among patients with (58%) and without UHD (49%). Factors associated with a decrease of UHC were age > 65 years (p = 0.01), no previous treatment for MBC (p = 0.0001) with a trend for the lack of CSC (p = 0.054). Among the 8 domains of the SF36 scale, only health change perception was improved (p = 0.01) and its predictive factors were treatment carried out as planned (p = 0.0004), pain care (p = 0.003), and lack of MBC progression (p = 0.0035). CONCLUSION: CSC can improve QoL in MBC. Painful patients might benefit more from CSC. UHC did not decrease for patients receiving CSC as expected possibly because of their important needs for clinical care.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hospitalização/tendências , Cuidados Paliativos/métodos , Qualidade de Vida/psicologia , Idoso , Feminino , Humanos , Masculino , Metástase Neoplásica , Estudos Prospectivos
7.
Clin Cancer Res ; 26(17): 4625-4632, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209570

RESUMO

PURPOSE: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical-surgical treatment. EXPERIMENTAL DESIGN: The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin-paclitaxel regimen ± nintedanib, and IDS, n = 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests. RESULTS: The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR = 0.13; 95% confidence interval (CI), 0.03-0.49] and complete IDS (no vs. yes, OR = 0.30; 95% CI, 0.11-0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery. CONCLUSIONS: The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance.See related commentary by May and Oza, p. 4432.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno Ca-125/sangue , Resistencia a Medicamentos Antineoplásicos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Intervalo Livre de Progressão
8.
Bull Cancer ; 105(9): 763-770, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-30097280

RESUMO

Advances in early detection and treatment have pushed in a few decades the management of cancers from a management model of the end of life to the management of a chronic disease. This evolution has accelerated the development of supportive care in two directions, firstly towards the best possible support to the end of life in advanced cancer patients (palliative care) and secondly to the limitation of treatment toxicities, the prevention of relapse and the return to life as "normal" as possible (care for after cancer). If palliative care now has a legitimacy and a solid regulatory base, this is not yet the case of supportive care in France. The content and organization differ depending on the institution, the choice of clinicians and patient preferences. Social networks and media convey messages that blur evidence-based practices. This article aims to review the facilitators and obstacles of this perspective.


Assuntos
Sobreviventes de Câncer , Neoplasias/terapia , Cuidados Paliativos/organização & administração , Assistência Terminal/organização & administração , Doença Crônica , Ensaios Clínicos como Assunto , Detecção Precoce de Câncer , Prática Clínica Baseada em Evidências , Humanos , Oncologia/economia , Oncologia/legislação & jurisprudência , Oncologia/organização & administração , Metanálise como Assunto , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Objetivos Organizacionais , Cuidados Paliativos/legislação & jurisprudência , Preferência do Paciente , Guias de Prática Clínica como Assunto , Apoio à Pesquisa como Assunto , Apoio Social , Fatores Socioeconômicos , Assistência Terminal/legislação & jurisprudência
10.
Breast Cancer Res Treat ; 131(1): 127-35, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21947680

RESUMO

To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80 mg/m(2), days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. All 130 randomized patients were evaluable for safety. Dose reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A and 34% in arm B during cycles 1-6. In arm A, there were significantly more toxicity-related dose reductions (cycles 1-6: 82 vs. 67%, respectively; P = 0.05) and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Paclitaxel/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...