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1.
Br J Cancer ; 119(4): 424-428, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29872148

RESUMO

BACKGROUND: Triplet chemotherapy, with docetaxel-5FU-oxaliplatin (TEFOX), has yielded promising results in patients with advanced and operable gastric adenocarcinoma. This may prove useful in treating signet ring cell carcinoma (SRCC), which is known to be chemoresistant and has a poor prognosis. We therefore evaluated TEFOX in patients with untreated advanced SRCC. METHODS: Patients with metastatic or locally advanced non-resectable SRCC were treated with TEFOX. Chemotherapy was administered every 14 days, with combined docetaxel (50 mg/m2) and oxaliplatin (85 mg/m2) followed by 5FU (2400 mg/m2). RESULTS: Among 65 patients enrolled, including 17 with linitis plastica, ORR and DCR were 66.1% and 87.6%, respectively. Median PFS and OS were 9.7 months (95% CI [6.9-11.4]) and 14.3 months (95% CI [11.6-21.6]) respectively. Twenty-six patients (40%) initially considered as unresectable had secondary resection (n = 24) or radiotherapy (n = 2) with curative intent, with median PFS and OS of 12.4 and 26.2 months, respectively. CONCLUSIONS: TEFOX appears to be effective as first-line treatment in advanced gastric SRCC and has an acceptable safety profile. It allowed a curative intent approach in 40% of patients. Considering the low chemosensitivity of SRCC reported with other chemotherapy regimens and pending for randomised studies, TEFOX might be an option in advanced gastric SRCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Docetaxel/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células em Anel de Sinete/cirurgia , Docetaxel/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
2.
Br J Cancer ; 113(7): 989-95, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26372701

RESUMO

BACKGROUND: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA. METHODS: From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity. RESULTS: Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1-12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI: 6.2-9.7) and median progression-free survival was 5.1 months (95% CI: 3.2-6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI: 16-21). No toxic deaths occurred. Grade 3-4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%). CONCLUSIONS: A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Gencitabina , Neoplasias Pancreáticas
3.
Rev Prat ; 65(6): 789-92, 2015 Jun.
Artigo em Francês | MEDLINE | ID: mdl-26298901

RESUMO

Adjuvant treatment has clearly demonstrated its efficacy and safety in resected colon cancer patients, saving thousands of lives every year worldwide. Six months adjuvant chemotherapy combining 5FU and oxaliplatin (FOLFOX or XELOX regimens) is indicated in stage III colon cancer after surgical removal of the primary tumor. The benefit of adjuvant chemotherapy seems less evident in stage II colon cancer, but this treatment should be discussed in patients with "high risk" factors for recurrence. Patient's age is also an important factor for adjuvant treatment decision. The challenge in the future will be to establish predictive and prognostic scores able to offer an even more personalized adjuvant therapeutic approach.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Algoritmos , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Humanos , Recidiva Local de Neoplasia/prevenção & controle
4.
Gastric Cancer ; 17(2): 341-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23739764

RESUMO

BACKGROUND: Docetaxel-cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC. METHODS: Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m(2)), oxaliplatin (85 mg/m(2)), and leucovorin (40 mg/m(2)) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m(2)) every 2 weeks. RESULTS: Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %). CONCLUSION: TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem
5.
J Am Heart Assoc ; 10(23): e020475, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34816734

RESUMO

Background The development of carcinoid heart disease (CaHD) is still relatively unclear. It is difficult to define an optimal follow-up for patients without any cardiac involvement at baseline. The aim of this study was to assess the prevalence and natural history of CaHD by annual echocardiographic examinations. Methods and Results We studied 137 consecutive patients (61±12 years, 53% men) with proven digestive endocrine tumor and carcinoid syndrome between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right-sided and left-sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CaHD. An increase of 25% of the score was considered to be significant. Mean follow-up was 54±45 months. Prevalence of CaHD was 27% at baseline and 32% at 5-year follow-up. Disease progression was reported in 28% of patients with initial CaHD followed up for >2 years (n=25). In patients without any cardiac involvement at baseline, occurrence of disease was 21%. CaHD occurred >5 years from the initial echocardiographic examination in 42% of our cases, especially in patients presenting with new recurrence of a digestive endocrine tumor. An increase of urinary 5-hydroxyindoleacetic acid by 25% during follow-up was identified as an independent predictor of CaHD occurrence during follow-up (hazard ratio [HR], 5.81; 95% CI, 1.19-28.38; P=0.03), as well as a maximum value of urinary 5-hydroxyindoleacetic acid >205 mg/24 h during follow-up (HR, 8.41; 95% CI, 1.64-43.07; P=0.01). Conclusions Our study demonstrates that in patients without initial CaHD, cardiac involvement may occur late and is related to serotonin. Our data emphasize the need for cardiologic follow-up in patients with recurrence of the tumor process.


Assuntos
Doença Cardíaca Carcinoide , Progressão da Doença , Idoso , Doença Cardíaca Carcinoide/diagnóstico por imagem , Doença Cardíaca Carcinoide/patologia , Doença Cardíaca Carcinoide/terapia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Clin Cancer Res ; 27(20): 5638-5646, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34083233

RESUMO

PURPOSE: Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial. EXPERIMENTAL DESIGN: ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III). RESULTS: Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied (n = 1017) versus not analyzed (n = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients (P = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13-2.12, P = 0.006) and OS (HR = 1.65, 95% CI 1.12-2.43, P = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1-3/N1 tumors. CONCLUSIONS: In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker.See related commentary by Bent and Kopetz, p. 5449.


Assuntos
DNA Tumoral Circulante/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/tratamento farmacológico , Idoso , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Duração da Terapia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos
7.
Stat Methods Med Res ; 29(2): 541-567, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30963815

RESUMO

BACKGROUND: Building tools to support personalized medicine needs to model medical decision-making. For this purpose, both expert and real world data provide a rich source of information. Currently, machine learning techniques are developing to select relevant variables for decision-making. Rather than using data-driven analysis alone, eliciting prior information from physicians related to their medical decision-making processes can be useful in variable selection. Our framework is electronic health records data on repeated dose adjustment of Irinotecan for the treatment of metastatic colorectal cancer. We propose a method that incorporates elicited expert weights associated with variables involved in dose reduction decisions into the Stochastic Search Variable Selection (SSVS), a Bayesian variable selection method, by using a power prior. METHODS: Clinician experts were first asked to provide numerical clinical relevance weights to express their beliefs about the importance of each variable in their medical decision making. Then, we modeled the link between repeated dose reduction, patient characteristics, and toxicities by assuming a logistic mixed-effects model. Simulated data were generated based on the elicited weights and combined with the observed dose reduction data via a power prior. We compared the Bayesian power prior-based SSVS performance to the usual SSVS in our case study, including a sensitivity analysis using the power prior parameter. RESULTS: The selected variables differ when using only expert knowledge, only the usual SSVS, or combining both. Our method enables one to select rare variables that may be missed using only the observed data and to discard variables that appear to be relevant based on the data but not relevant from the expert perspective. CONCLUSION: We introduce an innovative Bayesian variable selection method that adaptively combines elicited expert information and real world data. The method selects a set of variables relevant to model medical decision process.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Prova Pericial/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Tomada de Decisão Clínica , Relação Dose-Resposta a Droga , Registros Eletrônicos de Saúde , Feminino , Humanos , Irinotecano/administração & dosagem , Modelos Logísticos , Masculino , Metástase Neoplásica/tratamento farmacológico , Medicina de Precisão , Projetos de Pesquisa , Inibidores da Topoisomerase I/administração & dosagem
8.
BMC Cancer ; 9: 347, 2009 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-19785749

RESUMO

BACKGROUND: The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3rd or later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin. METHODS: Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days. RESULTS: Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2nd or 3rd line and 25% and 55% in 4th or later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients. CONCLUSION: This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Bevacizumab , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
9.
Eur J Cancer ; 123: 92-100, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678771

RESUMO

BACKGROUND: Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity. METHODS: This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7-30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%. RESULTS: Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5-43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14-23), 17 (13-22), and 51 (33-60) months. The most common grade III-IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%). CONCLUSIONS: The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease. TRIAL REGISTRATION: NCT01678664 (clinicaltrials.gov).


Assuntos
Antineoplásicos/uso terapêutico , Embolização Terapêutica , Everolimo/uso terapêutico , Neoplasias Gastrointestinais/patologia , Artéria Hepática , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Quimioembolização Terapêutica , Doxorrubicina/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Intervalo Livre de Progressão , Estreptozocina/administração & dosagem
10.
Am J Cardiol ; 101(7): 1035-8, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-18359327

RESUMO

The aim of this study was to assess (1) the incidence of patent foramen ovale (PFO) in carcinoid syndrome (CS) and (2) the feasibility of percutaneous closure procedure in selected patients with CS. One hundred eight patients were prospectively studied: 54 with CS and an age- and gender-matched control group. All patients underwent conventional and contrast echocardiography. Patients with clinical signs of dyspnea (New York Heart Association class > or =III), cyanosis, carcinoid heart disease (CHD), and severe PFO were referred for the percutaneous closure of PFO. The prevalence of PFO was 41% in patients with CS and 22% in the control group (p = 0.03) and was significantly higher in patients with CHD (59%, p = 0.009). Four patients (14% of those with CHD) were referred for the percutaneous closure of PFO, and 3 patients ultimately underwent PFO closure (using Amplatzer septal occluders). At 6-month follow-up, New York Heart Association class was improved in all patients, as well as arterial blood gas results (p = 0.04) and 6-minute walking distance (p = 0.03), but all patients presented residual right-to-left shunts. In conclusion, this prospective study demonstrates that in patients with CHD, the prevalence of PFO is high and that percutaneous closure of PFO is feasible, with a reduction in symptoms but with residual shunting.


Assuntos
Doença Cardíaca Carcinoide/epidemiologia , Forame Oval Patente/epidemiologia , Forame Oval Patente/terapia , Implantação de Prótese , Idoso , Doença Cardíaca Carcinoide/complicações , Cateterismo Cardíaco , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Forame Oval Patente/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Resultado do Tratamento
11.
Clin Res Hepatol Gastroenterol ; 42(3): 255-260, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29233520

RESUMO

INTRODUCTION: Hepatic arterial infusion (HAI) chemotherapy with oxaliplatin is an accepted option in the management of colorectal cancer (CRC) with dominant liver metastases (LM). However, despite prolonged control, some patients experience disease progression. On the other hand, oxaliplatin leads to dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. We evaluated treatment outcomes in patients receiving second-line HAI with 5-FU or mitomycin C, after first-line HAI of oxaliplatin in heavily pretreated patients. MATERIAL AND METHODS: Between March 2010 and June 2016, this observational study included 24 patients with unresectable CRC LM and treated with HAI of 5-FU (17 patients) or mitomycin C (7 patients), after HAI of oxaliplatin. RESULTS: Mean age was 61.7 years. Forty-two percent of patients (10/24) had extra-hepatic metastases and 75% (18/24) at least 8 liver metastases. Including HAI of oxaliplatin, all patients had previously received at least 2 lines of chemotherapy±targeted agents (100%) and 96% (23/24) received concomitant systemic therapies together with HAI of 5-FU or mitomycin C. The overall objective response rate and disease control rate were, respectively, 42% (10/24) and 71% (17/24). Median progression-free survival and overall survival (OS) were, respectively, 5.6 and 25.8 months; hepatic progression-free survival was 8.5months. Thirteen percent (3/24) of the patients received further curative intent treatment after HAI 5-FU and mitomycin C. No toxic death occurred and the toxicity profile was acceptable. CONCLUSIONS: HAI of 5-FU or mitomycin C is an alternative option in patients with predominant CRC LM, when they experience disease progression or do not tolerate HAI of oxaliplatin.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Mitomicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/efeitos adversos , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Oxaliplatina/administração & dosagem , Estudos Retrospectivos , Falha de Tratamento
12.
Dig Liver Dis ; 50(2): 195-198, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29258812

RESUMO

INTRODUCTION: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. AIM: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC. MATERIALS AND METHODS: The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy. RESULTS: A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response. CONCLUSION: The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Carcinoma Neuroendócrino/mortalidade , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , França , Humanos , Neoplasias Intestinais/mortalidade , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Projetos de Pesquisa , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
13.
J Clin Oncol ; 36(15): 1469-1477, 2018 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-29620995

RESUMO

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Oxaliplatina/administração & dosagem , Idoso , Quimioterapia Adjuvante , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , França , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
14.
Gastroenterol Clin Biol ; 31(4): 445-7, 2007 Apr.
Artigo em Francês | MEDLINE | ID: mdl-17483787

RESUMO

Undifferentiated neuroendocrine tumors are rare, and are characteristically aggressive with a poor prognosis. Most patients have metastatic disease at diagnosis, and cannot undergo curative surgical treatment. A chemotherapy regimen combining etoposide plus cisplatin is currently considered to be the reference treatment. We report two cases of poorly differentiated neuroendocrine tumors localized in the anal canal and treated by chemotherapy and radiotherapy resulting in prolonged complete local remission and preventing extended surgical excision.


Assuntos
Neoplasias do Ânus/terapia , Neoplasias Encefálicas/secundário , Tumores Neuroendócrinos/terapia , Corticosteroides/uso terapêutico , Idoso , Canal Anal/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/patologia , Neoplasias do Ânus/radioterapia , Biópsia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/secundário , Dosagem Radioterapêutica , Indução de Remissão , Fatores de Tempo
15.
Gastroenterol Clin Biol ; 31(12): 1139-42, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18176374

RESUMO

AIM: To estimate the risk of venous thrombosis associated with pancreatic adenocarcinoma and its consequences on treatment and survival. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 90 patients (49 males, 41 females - median age: 67 years [range: 37-94]). Pancreatic adenocarcinoma was histologically proved in 72 patients (81%) and was metastatic in 49 patients (54.4%). A venous thrombosis was observed in 24 patients (26.7%). A pulmonary embolism occurred in 4 patients with 2 deaths. The risk of venous thrombosis was significantly reduced by the use of anti-thrombotic prophylaxis (HR: 0.03 [95CI: 0.003-0.27]) and increased among patients with a biological inflammatory syndrome (HR: 9.0 [95CI: 2.30-34.4]) and metastatic disease (HR: 4.4 [95CI: 1.1-17.9]). Overall survival was not different between patients with (6.6 months) or without (6.1 months) venous thrombosis. CONCLUSION: The risk of venous thrombosis is important and may delay the treatment in patients with advanced pancreatic carcinoma. Some patients with high risk of venous thrombosis may benefit from a prophylactic anticoagulant treatment.


Assuntos
Adenocarcinoma/complicações , Neoplasias Pancreáticas/complicações , Trombose Venosa/etiologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Cateteres de Demora , Causas de Morte , Estudos de Coortes , Feminino , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Trombose Venosa/prevenção & controle
16.
Gastroenterol Clin Biol ; 31(2): 151-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17347623

RESUMO

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos
17.
Eur J Cancer ; 74: 98-108, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27825697

RESUMO

AIM: Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis. METHOD: Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL. CONCLUSION: The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Avaliação Geriátrica , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Masculino , Metástase Neoplásica , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
18.
Am Heart J ; 151(5): 1129.e1-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16644350

RESUMO

BACKGROUND AND OBJECTIVE: Carcinoid syndrome may involve right carcinoid heart disease (CHD), secondary to the release of vasoactive substances. Left CHD is rare, as the inactivation of serotonin by the lung protects the left heart. We attempted to evaluate the prevalence of CHD and patent foramen ovale (PFO) with serial contrast transthoracic echocardiographic studies and to determine the markers of right and left CHD progression. METHODS: Forty-one consecutive patients with proved digestive endocrine tumor and carcinoid syndrome were prospectively enrolled. All patients underwent serial conventional and contrast transthoracic echocardiographic studies. Right and left CHD, PFO, radiological examinations, and biological carcinoid markers were systematically assessed. RESULTS: Left CHD was present in 5 patients at baseline and in 13 patients (32%) during follow-up (P = .03). The 13 patients with left CHD also had PFO, and no left CHD occurred without PFO (P < .0001). Right CHD was present in 16 patients (39%) at baseline and in 25 patients (61%) at the end of follow-up (P = .04). The prevalence of right and left CHD was significantly higher in patients with PFO (88% and 76%, respectively; P < .04). A progression of right and left CHD was present, respectively, in 19 and 9 patients but was mainly found in patients with PFO (15 and 9 patients; P < .0001). The main marker of CHD progression was the presence of PFO (odds ratio 44.2, 95% confidence interval 4.4-447.7; P = .001). CONCLUSIONS: PFO is a new marker of CHD progression and should be systematically assessed with routine contrast transthoracic echocardiography in patients with carcinoid syndrome to determine patients at high risk of CHD progression.


Assuntos
Doença Cardíaca Carcinoide/complicações , Doença Cardíaca Carcinoide/diagnóstico por imagem , Ecocardiografia , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico por imagem , Adulto , Idoso , Doença Cardíaca Carcinoide/epidemiologia , Progressão da Doença , Feminino , Comunicação Interatrial/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos
19.
Ther Adv Med Oncol ; 8(5): 383-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27583030

RESUMO

VIPoma is a rare neuroendocrine tumor (NET) with a high potential to develop hepatic metastases and poor prognosis. The primitive tumor is nonsymptomatic and usually localized within the pancreas. Liver metastasis drives the prognosis and induces profuse watery diarrhea or renal failure. We herein present severe renal failure or diarrhea in two patients hospitalized in intensive care justifying emergency treatment of liver metastasis. The two patients experienced severe diarrhea due to a hypersecretion of vasoactive intestinal peptide (VIP) from liver metastasis released into the blood circulation. Therapeutic management was discussed and liver transarterial chemoembolization (TACE) was performed with chemotherapy-loaded embospheres, which cause necrosis of tumor lesions. TACE controlled the hormonal syndrome and made patients eligible for curative surgery. Tumor necrosis occurred and VIP levels collapsed. Surgery was performed in one of the two cases after TACE and the patient was considered in remission. Both patients were still alive after 3 years of follow up. Thus, TACE is feasible and appears to be an effective emergency treatment in patients with a VIP-hormonal syndrome due to liver metastases. Despite the biological disorder due to the hormonal secretion, an aggressive approach is warranted in VIP liver metastasis.

20.
Eur J Cancer ; 68: 163-172, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27768923

RESUMO

BACKGROUND: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m2) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. METHODS: Irinotecan (180 mg/m2), 5-fluorouracil (2800 mg/m2) and oxaliplatin (85 mg/m2) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models. RESULTS: Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33-76 years, with a median of 12 liver metastases (LMs) (2-50), involving five segments (1-8). Ten patients had a late response, and 31 patients had no response. Grade 3-4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation-odds ratio (OR): 6.0 (1.2-29.8; p = 0.029)-and LM diameter ≤57 mm-OR: 5.3 (1.1-25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection-OR: 11.8 (1.4-100.2; p = 0.024) and overall survival-hazard ratio: 0.39 (0.17-0.88; p = 0.023) in multivariate analyses. CONCLUSIONS: Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making. Protocol numbers: EUDRACT 2007-004632-24 NCT00852228.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Irinotecano , Neoplasias Hepáticas/secundário , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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