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1.
Int J Mol Sci ; 21(7)2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32260578

RESUMO

Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.


Assuntos
Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Neoplasias Renais/terapia , Animais , Carcinoma de Células Renais/imunologia , Ensaios Clínicos como Assunto , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico
2.
Int J Cancer ; 140(1): 142-148, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27623354

RESUMO

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti-angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation). PD-L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p = 0.03). PD-L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p = 0.01), metastases at diagnosis (p = 0.01), a sarcomatoid component (p = 0.04), overexpression of VEGF (p = 0.006), and cytoplasmic PAR-3 expression (p = 0.01). PD-L1 expression was also associated with dense PD-1 expression (p = 0.007) and with ccRCC with 0 or 1 alteration(s) (non-inactivated VHL tumors; p = 0.007) that remained significant after multivariate analysis (p = 0.004 and p = 0.024, respectively). Interestingly, all wild-type VHL tumors (no VHL gene alteration, 11.2%) expressed PD-L1. In this study, we found PD-L1 expression to be associated with noninactivated VHL tumors and in particular wild-type VHL ccRCC, which may benefit from therapies inhibiting PD-L1/PD-1.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
3.
Eur J Nucl Med Mol Imaging ; 43(4): 635-43, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26455499

RESUMO

PURPOSE: Tumoural portal vein thrombosis (PVT) is a major prognostic factor in hepatocellular carcinoma (HCC). The efficacy of sorafenib, the only treatment approved at an advanced stage, is limited. Based on previous data, selective internal radiation therapy (SIRT), or (90)Y radioembolization, seems an interesting option. We aimed to compare both treatments in this population. METHODS: We retrospectively compared patients treated in two centres for HCC with tumoural PVT. We compared overall survival (OS) between patients treated with SIRT and patients treated with sorafenib. Analyses were performed before and after 1:1 matching with a propensity score for controlling indication bias, using a Cox proportional hazards model. RESULTS: A total of 151 patients were analysed, 34 patients treated with SIRT and 117 patients treated with sorafenib only. In the whole population, SIRT was associated with a higher median OS as compared with sorafenib: 18.8 vs 6.5 months (log-rank p < 0.001). There was an imbalance of baseline characteristics between patients treated by SIRT and sorafenib, which justified patient matching with use of a propensity score: 24 patients treated with SIRT could be matched with 24 patients treated with sorafenib. OS was estimated with a median of 26.2 vs 8.7 months in patients treated with SIRT vs sorafenib, respectively (log-rank p = 0.054). Before and after patient matching, the adjusted hazard ratio related to treatment by SIRT was estimated at 0.62 [95 % confidence interval (CI) 0.39-0.97] (p = 0.037) and 0.40 (95 % CI 0.19-0.82) (p = 0.013), respectively. CONCLUSION: SIRT seems more effective than sorafenib in patients presenting with HCC and tumoural PVT. This hypothesis is being tested in prospective randomized trials.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Trombose Venosa/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Veia Porta/patologia , Compostos Radiofarmacêuticos/efeitos adversos , Sorafenibe , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Radioisótopos de Ítrio/efeitos adversos
4.
J Vasc Interv Radiol ; 26(12): 1874-78.e2, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26596183

RESUMO

Synergy between yttrium-90 (90Y) and antineoplastic drugs was investigated. Viability of HepaRG (hepatocellular carcinoma) and HuCCT1 (cholangiocarcinoma) cells was studied through a tetrazolium dye reduction assay. A combination index (CI) was calculated, with CI < 1 denoting synergy and CI > 1 denoting antagonism. In HepaRG cells, gemcitabine showed synergy with 90Y (CI = 0.70 [95% confidence interval = 0.65-0.75]), whereas oxaliplatin (CI = 1.15 [1.08-1.21]), paclitaxel (CI = 1.26 [1.15-1.37]), and sorafenib (CI = 1.77 [1.65-1.89]) showed antagonism. In HuCCT1 cells, gemcitabine (CI = 0.54 [0.50-0.58]) and oxaliplatin (CI = 0.86 [0.82-0.90]) showed synergy with 90Y, whereas paclitaxel (CI = 1.18 [1.09-1.27]) and sorafenib (CI = 1.21 [1.12-1.30]) showed antagonism. These results suggest that gemcitabine and oxaliplatin should be tested in combination with 90Y radioembolization for treatment of liver cancer.


Assuntos
Carcinoma Hepatocelular/terapia , Colangiocarcinoma/terapia , Desoxicitidina/análogos & derivados , Niacinamida/análogos & derivados , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Radioisótopos de Ítrio/uso terapêutico , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia/métodos , Colangiocarcinoma/patologia , Desoxicitidina/administração & dosagem , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Sinergismo Farmacológico , Humanos , Niacinamida/administração & dosagem , Tolerância a Radiação/efeitos dos fármacos , Compostos Radiofarmacêuticos/administração & dosagem , Sorafenibe , Gencitabina
5.
Mol Oncol ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287892

RESUMO

Erb-b2 receptor tyrosine kinase 2 (ERBB2)-activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone-receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three-color Crystal dPCR™ naica® platform with a two-step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma-based monitoring of ERBB2 mutational status in patients with MBC.

6.
Clin Chim Acta ; 545: 117366, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37105452

RESUMO

BACKGROUND: Early detection of ESR1 mutations is a key element for better personalization of the management of patients with HR+/HER2- Metastatic Breast Cancer (MBC). Analysis of circulating tumor DNA from liquid biopsies is a particularly well-suited strategy for longitudinal monitoring of such patients. MATERIALS AND METHODS: Using the naica® three-color digital PCR platform, we developed a screening assay allowing the detection of 11 ESR1 mutations and designed a sequential strategy for precise mutation identification. We then applied this strategy in the analysis of plasma circulating cell-free DNA from 109 HR+/HER2- MBC patients and performed a double-blind comparison study on a subset of patients with the multiplex assay used at the Institut Curie (IC) for the PADA-1 study. RESULTS: Thirty-one patients (28.4%) harboured at least one ESR1 mutation, with the following frequencies: D538G (41.03%), Y537S (25.64%), E380Q (10.26%), Y537N (10.26%), "(536-540)" (7.69%), Y537C (2.56%), and L536R (2.56%). The presence of ESR1 mutation(s) was significantly associated with liver metastases (p = 0.0091). A very good agreement (91%) was observed with the IC assay. CONCLUSION: Our assays have proven to be robust and highly sensitive and are very well-suited for monitoring ESR1 mutations in the plasma of MBC patients.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mutação , DNA Tumoral Circulante/genética , Reação em Cadeia da Polimerase Multiplex
7.
Eur J Cancer ; 175: 43-53, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088671

RESUMO

BACKGROUND: Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). METHODS: In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities. RESULTS: Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (< or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients. CONCLUSION: This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/patologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Taxoides , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
8.
J Oncol ; 2022: 3449660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222642

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods. This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models. RESULTS: ORR was 51% (n = 23) at first ICI therapy (ICI-1) and 16% (n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8-23.5) and 3.5 months (95% CI, 2.8-9.7), and median overall survival was not reached (NR) (95% CI, 37.8-NR) and 24 months (95% CI, 9.9-NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months (p=0.07) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens (p=0.07). CONCLUSION: Rechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.

9.
Int J Biol Markers ; 36(2): 57-63, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34027694

RESUMO

PURPOSE: Genomic signatures, such as EndoPredict®, may help clinicians to decide which adjuvant treatment is the most appropriate. METHODS: We propose the EndoPredict® assay for unclear cases of adjuvant treatment in patients treated in our comprehensive cancer center. We prospectively and retrospectively report the decision of adjuvant treatment before and after the EndoPredict® assay, respectively, compared to the PREDICT's tool scores. RESULTS: From November 2016 to March 2019, 159 breast cancer tumors were analyzed and presented before and after the EndoPredict® assay. Before the EndoPredict® results, clinicians recommended chemotherapy for 57 patients (57/159, 36%). A total of 108 patients (108/159, 68%) were classified as EPclin high-risk score. There was only a slight agreement between clinicians' decisions and EPclin risk score. The EPclin score led to 37% changes in treatment (59/159); chemotherapy was favored in 80% of cases (47/59). The PREDICT tool recommended chemotherapy for 16 high-risk patients (16/159, 10%). CONCLUSION: Although genomic tests were developed in order to de-escalate adjuvant treatment, in our comprehensive cancer center the use of the EndoPredict® assay led to an increase in prescribed chemotherapy.


Assuntos
Quimioterapia Adjuvante/métodos , Tomada de Decisões/efeitos dos fármacos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
10.
Sci Rep ; 11(1): 17316, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453076

RESUMO

With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2- metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542-546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2- MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Adolescente , Sequência de Bases , Neoplasias da Mama/diagnóstico , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Mutação , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Adulto Jovem
11.
Eur J Cancer ; 151: 106-114, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975058

RESUMO

PURPOSE: Fumarate hydratase-deficient (FHdef) renal cell carcinoma (RCC) is a rare entity associated with the hereditary leiomyomatosis and RCC syndrome with no standard therapy approved. The aim of this retrospective study was to evaluate the efficacy of different systemic treatments in this population. METHODS: We performed a multicentre retrospective analysis of Fhdef RCC patients to determine the response to systemic treatments. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and overall survival (OS). The two latter were estimated using the Kaplan-Meier method. RESULTS: Twenty-four Fhdef RCC patients were identified, and 21 under systemic therapy were included in the analysis: ten received cabozantinib, 14 received sunitinib, nine received "other antiangiogenics" (sorafenib, pazopanib, and axitinib), three received erlotinib-bevacizumab (E-B), three received mTOR inhibitors, and 11 received immune checkpoint blockers (ICBs). ORR for treatments were 50% for cabozantinib, 43% for sunitinib, 63% for "other antiangiogenics," and 30% for E-B, whereas ORR was 0% for mTOR inhibitors and 18% for ICBs. The median TTF (mTTF) was significantly higher with antiangiogenics (11.6 months) than with mTOR inhibitors (4.4 months) or ICBs (2.7 months). In the first-line setting, antiangiogenics presented a higher ORR compared with nivolumab-ipilimumab (64% versus 25%) and a significantly superior mTTF (11.0 months vs 2.5 months; p = 0.0027). The median OS from the start of the first systemic treatment was 44.0 months (95% confidence interval: 13.0-95.0). CONCLUSIONS: We report the first European retrospective study of Fhdef RCC patients treated with systemic therapy with a remarkably long median OS of 44.0 months. Our results suggest that antiangiogenics may be superior to ICB/mTOR inhibitors in this population.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Biomarcadores Tumorais/genética , Fumarato Hidratase/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Inibidores da Angiogênese/efeitos adversos , Biomarcadores Tumorais/deficiência , Progressão da Doença , Feminino , França , Fumarato Hidratase/deficiência , Predisposição Genética para Doença , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Renais/enzimologia , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fenótipo , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Espanha , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Falha de Tratamento , Adulto Jovem
12.
Eur J Cancer ; 153: 223-233, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214937

RESUMO

AIMS: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. METHODS: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. RESULTS: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. CONCLUSIONS: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases. CLINICAL TRIAL REGISTRATION: NCT02614794.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Oxazóis/uso terapêutico , Piridinas/uso terapêutico , Quinazolinas/uso terapêutico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Capecitabina/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Oxazóis/farmacologia , Piridinas/farmacologia , Qualidade de Vida , Quinazolinas/farmacologia , Trastuzumab/farmacologia , Resultado do Tratamento , Adulto Jovem
13.
Presse Med ; 48(10): 1131-1137, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31151842

RESUMO

Managing endocrine resistance and resistance to endocrine therapy for ER+ HER2- breast cancer with the CDK 4/6 inhibitors in the metastatic setting. New antibodies drug conjugates for HER2+ and TNBC. Targeting DNA damage and synthetic lethality strategies with PARP inhibitors for breast cancer patients harboring BRCA mutation. Immunotherapies in 1st line metastatic setting of TNBC.


Assuntos
Neoplasias da Mama/terapia , Neoplasias da Mama/química , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Humanos , Imunoconjugados/uso terapêutico , Imunoterapia/métodos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Cancer Nurs ; 41(5): 418-423, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28731881

RESUMO

BACKGROUND: Sorafenib is the standard treatment of advanced hepatocellular carcinoma. Because of its unique toxicities, improving patients' tolerance merits close follow-up. Nurses can play a crucial role by leading a patient educational program (EP). OBJECTIVES: The aim of this study was to assess whether adding EP to usual care (UC) improves patient's care. METHODS: Since 2011, oncologists referred patients treated by sorafenib to the EP led by clinical nurses. The EP included a visit before the first administration, weekly telephone calls, and a visit with the nurse before each oncologist consultation. We retrospectively compared patients in the EP with those in UC followed by an oncologist and patients included in a clinical trial. RESULTS: Since 2005, 129 patients were treated with sorafenib for hepatocellular carcinoma: 31 in the EP (24%), 22 in a clinical trial (17%), and 76 with UC (59%). Seventy-one percent of the patients in the EP had toxicities identified during a telephone call, which prompted symptomatic measures in 65% of the patients, leading to treatment modification before the planned on-site visit in 29% of the patients. Educational program patients required fewer dose reductions (39% vs 61% for UC, P = .04), and median time to first dose reduction was shorter with EP than with UC (25 vs 45 days, P = .036). CONCLUSIONS: This study suggests a clinical benefit of EP related to improved toxicity management of sorafenib that resulted in fewer dose reductions. IMPLICATIONS FOR PRACTICE: Patients treated with sorafenib may benefit from an EP. Different types of EP should be compared prospectively, focusing on patients' quality of life.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/enfermagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enfermagem , Educação de Pacientes como Assunto , Sorafenibe/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Estudos Retrospectivos
16.
Bull Cancer ; 103(11): 941-948, 2016 Nov.
Artigo em Francês | MEDLINE | ID: mdl-27817860

RESUMO

BACKGROUND: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC). Due to its peculiar toxicities, improving patient's tolerance may need close follow-up. Nurses can play a crucial role, by driving a patient education program (EP). We aimed to prove that adding EP to usual care (UC) improves patient's care. METHODS: Since 2011, oncologists referred patients treated by sorafenib to the EP, driven by clinical nurses. It consisted in a visit before first administration, weekly telephone calls and a visit before each oncologist consultation. We retrospectively compared patients followed by the EP to those followed by oncologist in usual care (UC) and patients included in a clinical trial (CT). RESULTS: Since 2005, 129 patients were treated with sorafenib for HCC, 31 (24%) in the EP, 22 (17%) in CT and 76 (59%) with UC. Seventy-one percent of patients in the EP had toxicities identified during a telephone call, which prompted symptomatic measures in 65% of patients, leading to treatment modification before the planned on-site visit in 29% of patients. EP patients required less dose reductions (39% vs. 61% for UC, P=0.04), and median time to first dose reduction was shorter with EP than with UC (25 days vs. 45 days, P=0.036). CONCLUSION: This study suggests a clinical benefit of EP, with a better toxicity's management of sorafenib, leading to less dose reduction. Different types of EP should be compared prospectively, focusing on quality of life.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Padrões de Prática em Enfermagem , Inibidores de Proteínas Quinases/efeitos adversos , Administração Oral , Idoso , Antineoplásicos/administração & dosagem , Astenia/induzido quimicamente , Astenia/enfermagem , Carcinoma Hepatocelular/enfermagem , Diarreia/induzido quimicamente , Diarreia/enfermagem , Feminino , Síndrome Mão-Pé/enfermagem , Humanos , Neoplasias Hepáticas/enfermagem , Masculino , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Educação de Pacientes como Assunto , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Estudos Retrospectivos , Sorafenibe
18.
Cancer Chemother Pharmacol ; 75(1): 215-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25477009

RESUMO

PURPOSE: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). The peak incidence of HCC is around 70 years. We aimed to evaluate safety and efficacy of sorafenib in the elderly population. METHODS: We retrospectively reviewed data from patients treated with sorafenib for HCC at our institution. We compared safety and efficacy data across different age groups. RESULTS: Since 2005, 129 patients were treated, 78 (60.5 %) were <70 years old and 51 (39.5 %) were ≥70. The frequency of dose reduction was similar between the two groups (48.7 vs. 58.8 %), as was the occurrence of severe toxicities (41.0 vs. 51.0 %) and hospitalization due to toxicity (9.0 vs. 13.7 %). However, asthenia and bleeding were more frequent in the elderly. The higher frequency of bleeding was explained by concomitant antiplatelet treatments, and major asthenia was frequent in PS1 elderly patients. There was a trend toward less frequent interruption of treatment in the younger group (25.6 vs. 39.2 %) and significantly less frequent definitive discontinuation of treatment due to toxicity (24.4 vs. 45.1 %). Median progression-free survival was 5.6 months in both age groups, while median overall survival was 9.6 months in the younger age group and 12.6 months in the older age group. CONCLUSION: Sorafenib showed similar results in terms of safety and efficacy in the elderly and younger HCC populations. Careful baseline evaluation is needed for patient's selection in the elderly population, including discussion about antiplatelet therapy discontinuation and caution in PS1 patients, as well as active management of toxicity.


Assuntos
Envelhecimento , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Trombose Venosa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Astenia/induzido quimicamente , Astenia/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Comorbidade , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Seguimentos , França/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Veia Porta , Estudos Retrospectivos , Sorafenibe , Análise de Sobrevida , Carga Tumoral , Trombose Venosa/epidemiologia
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