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1.
Support Care Cancer ; 32(6): 347, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743147

RESUMO

PURPOSE: This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations. METHODS: In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic). RESULTS: The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis. CONCLUSIONS: Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Padrões de Prática Médica , Humanos , Estudos Transversais , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Inquéritos e Questionários , Pessoa de Meia-Idade , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Assistência Ambulatorial/métodos , Neoplasias/tratamento farmacológico , Pacientes Ambulatoriais/estatística & dados numéricos
2.
Int J Cancer ; 152(9): 1894-1902, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36562310

RESUMO

Pancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.


Assuntos
Carcinoma Adenoescamoso , Neoplasias Pancreáticas , Masculino , Humanos , Idoso , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gencitabina , Desoxicitidina , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/induzido quimicamente , Estudos Prospectivos , Paclitaxel/uso terapêutico , Fluoruracila/uso terapêutico , Estudos Retrospectivos , Leucovorina/uso terapêutico , Neoplasias Pancreáticas
3.
Gastric Cancer ; 26(3): 425-437, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36881202

RESUMO

BACKGROUND: The optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma (OGA) remains challenging. METHODS: Patients treated with trastuzumab (T) plus platinum salts and fluoropyrimidine (F) as first-line chemotherapy between 2010 and 2020 for HER2-positive advanced OGA at 17 academic care centers in France, Italy, and Austria were included. The primary objective was the comparison of F + T vs T alone as maintenance regimen in terms of progression-free survival (PFS) and overall survival (OS) after a platinum-based chemotherapy induction + T. As secondary objective, PFS and OS between patients treated with reintroduction of initial chemotherapy or standard second-line chemotherapy at progression were assessed. RESULTS: Among the 157 patients included, 86 (55%) received F + T and 71 (45%) T alone as a maintenance regimen after a median of 4 months of induction chemotherapy. Median PFS from start of maintenance therapy was 5.1 months in both groups (95% CI 4.2-7.7 for F + T and 95% CI 3.7-7.5 for T alone; p = 0.60) and median OS was 15.2 (95% CI 10.9-19.1) and 17.0 months (95% CI 15.5-21.6) for F + T and T alone, respectively (p = 0.40). Of 112/157 patients (71%) receiving systemic therapy after progression under maintenance, 26/112 (23%) were treated with a reintroduction of initial chemotherapy + T and 86/112 (77%) with a standard second-line regimen. Here, median OS was significantly longer with the reintroduction (13.8 (95% CI 12.1-19.9) vs 9.0 months (95% CI 7.1-11.9); p = 0.007) as confirmed by multivariate analysis (HR 0.49; 95% CI 0.28-0.85; p = 0.01). CONCLUSION: No additional benefit of adding F to T monotherapy as a maintenance treatment could be observed. Reintroduction of initial therapy at first progression may be a feasible approach to preserve later treatment lines.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Quimioterapia de Indução , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica , Trastuzumab/uso terapêutico
4.
Br J Cancer ; 126(10): 1394-1400, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35094032

RESUMO

BACKGROUND: Gemcitabine (Gem) alone or with Nab-paclitaxel (Gem-Nab) is used as second-line treatment for metastatic pancreatic adenocarcinoma (mPA) after FOLFIRINOX (FFX) failure; however, no comparative data exist. This study evaluates the efficacy and safety of adding Nab-paclitaxel to Gem for mPA after FFX failure. METHODS: In this retrospective real-world multicenter study, from 2011 to 2019, patients with mPA receiving Gem-Nab (Gem 1000 mg/m² + Nab 125 mg/m², 3 out of 4 weeks) or Gem alone were included after progression on FFX. RESULTS: A total of 427 patients were included. Patients receiving Gem-Nab had more metastatic sites, peritoneal disease and less PS 2 (24% vs. 35%). After median follow-up of 22 months, Gem-Nab was associated with better disease control rate (DCR) (56% vs. 32%; P < 0.001), progression-free survival (PFS) (3.5 vs. 2.3 months; 95% CI: 0.43-0.65) and overall survival (OS) (7.1 vs. 4.7 months; 95% CI: 0.53-0.86). After multivariate analysis, Gem-Nab and PS 0/1 were associated with better OS and PFS. Grade 3/4 toxicity was more frequent with Gem-Nab (44% vs. 29%). CONCLUSION: In this study, Gem-Nab was associated with better DCR, PFS and OS compared with Gem alone in patients with mPA after FFX failure, at the cost of higher toxicity.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina , Oxaliplatina , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Gencitabina , Neoplasias Pancreáticas
5.
World J Surg Oncol ; 20(1): 131, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461290

RESUMO

BACKGROUND: BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-type tumors. Therapeutic decision-making for colorectal liver metastases (CRLM) harboring this mutation remains difficult due to the scarce literature. The aim was to study a large cohort of BRAF V600E-mutant CRLM patients in order to see if surgery extend overall survival among others prognostic factors. METHODS: BRAF V600E-mutant CRCs diagnosed with liver-only metastases, resected or not, were retrospectively identified between April 2008 and December 2017, in 25 French centers. Clinical, molecular, pathological characteristics and treatment features were collected. Overall survival (OS) was defined as the time from CRLM diagnosis to death from any cause. Cox proportional hazard models were used for statistical analysis. RESULTS: Among the 105 patients included, 79 (75%) received chemotherapy, 18 (17%) underwent upfront CRLM surgery, and 8 (8%) received exclusive best supportive care. CRLM surgery was performed in 49 (46.7%) patients. CRLM were mainly synchronous (90%) with bilobar presentation (61%). The median OS was 34 months (range, 28.9-67.3 months) for resected patients and 10.6 (6.7-12.5) months for unresected patients (P < 0.0001). In multivariate analysis, primary tumor surgery (hazard ratio (HR) = 0.349; 95% confidence interval (CI) 0.164-0.744, P = 0.0064) and CRLM resection (HR = 0.169; 95% CI 0.082-0.348, P < 0.0001) were associated with significantly better OS. CONCLUSIONS: In the era of systemic cytotoxic chemotherapies, liver surgery seems to extend OS in BRAF V600E-mutant CRCs with liver only metastases historical cohort.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas B-raf , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Hepatectomia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
6.
N Engl J Med ; 379(25): 2395-2406, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30575490

RESUMO

BACKGROUND: Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer. METHODS: We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety. RESULTS: At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis). CONCLUSIONS: Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135 ; EudraCT number, 2011-002026-52 .).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Oxaliplatina , Modelos de Riscos Proporcionais , Estudos Prospectivos , Gencitabina
7.
Int J Cancer ; 147(1): 285-296, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31970760

RESUMO

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Enzimas Reparadoras do DNA/deficiência , Enzimas Reparadoras do DNA/metabolismo , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/administração & dosagem , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
8.
Br J Cancer ; 123(4): 518-524, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32507854

RESUMO

BACKGROUND: Chemo-embolisation with drug-eluting beads loaded with irinotecan (DEBIRI) increased survival as compared with intravenous irinotecan in chemorefractory patients with liver-dominant metastases from colorectal cancer (LMCRC). First-line DEBIRI with systemic chemotherapy may increase survival and secondary resection. METHODS: In the FFCD-1201 single-arm Phase 2 study, patients with untreated, non-resectable LMCRC received DEBIRI plus mFOLFOX6. Four courses of DEBIRI were performed alternating right and left lobe or two sessions with both lobes treated during the same session. RESULTS: Fifty-seven patients were enrolled. Grade 3-5 toxicities were more frequent when both lobes were treated during the same session (90.5% versus 52.8%). Nine-month PFS rate was 53.6% (95% CI, 41.8-65.1%). The objective response rate (RECIST 1.1) was 73.2%, and the secondary R0 surgery was 33%. With a median follow-up of 38.3 months, median OS was 37.4 months (95% CI, 25.7-45.8), and median PFS 10.8 months (95% CI, 8.2-12.3). CONCLUSIONS: Front-line DEBIRI + mFOLFOX6 should not be recommended as the hypothesised 9-month PFS was not met. However, high response rate, deep responses, and prolonged OS encourage further evaluation in strategies integrating biologic agent, in particular in patients with secondary surgery as the main goal. CLINICAL TRIAL REGISTRATION: NCT01839877.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/terapia , Irinotecano/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
9.
BMC Cancer ; 20(1): 485, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471382

RESUMO

BACKGROUND: Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT. METHODS: This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574. DISCUSSION: The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Cooperação do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Protectomia/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia
10.
Oncologist ; 24(12): e1331-e1340, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31152084

RESUMO

BACKGROUND: BRAFV600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown. MATERIALS AND METHODS: We built a multicenter clinico-biological database gathering data from patients with BRAFV600E -mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model. RESULTS: We included 287 patients (median age, 67 years [28-95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97-27.04), and median progression-free survival in the first-line setting was 4.34 months (95% CI, 3.81-5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti-epidermal growth factor receptor) were not associated with overall and progression-free survival. Stage IV disease (synchronous metastases) and absence of curative-intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p = .009). CONCLUSION: Despite that BRAFV600E -mutant mCRCs are associated with poor overall and progression-free-survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAFV600E mCRC in day-to-day practice. IMPLICATIONS FOR PRACTICE: Mismatch repair (MMR) testing and resectability discussion in patients with BRAFV600E metastatic colorectal cancer (mCRC) should be performed in day-to-day practice to steer treatment decision making in patients with BRAFV600E -mutant mCRC.


Assuntos
Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica
11.
Ann Surg Oncol ; 26(1): 109-117, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30362063

RESUMO

BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
13.
Br J Cancer ; 115(3): 281-9, 2016 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-27404456

RESUMO

BACKGROUND: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). METHODS: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. RESULTS: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). CONCLUSIONS: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.


Assuntos
Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais
14.
Qual Life Res ; 25(7): 1713-23, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26615615

RESUMO

PURPOSE: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is currently an important parameter in the choice of treatment strategy for metastatic pancreatic adenocarcinoma (mPA) patients. However, previous research has shown that patients' self-reported health-related quality of life (HRQOL) scales provided additional prognostic information in homogeneous groups of patients with respect to ECOG-PS. The aim of this study was to identify HRQOL scales with independent prognostic value in mPA and to propose prognostic groups for these patients. METHODS: We analysed data from 98 chemotherapy-naive patients with histologically proven mPA recruited from 2007 to 2011 in the FIRGEM phase II study which aimed to compare the effectiveness of two chemotherapy regimen. HRQOL data were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. A random survival forest methodology was used to impute missing data and to identify major prognostic factors for overall survival. RESULTS: Baseline HRQOL assessment was completed by 60 % of patients (59/98). Twelve prognostic variables were identified. The three most important prognostic variables were fatigue, appetite loss, and role functioning, followed by three laboratory variables. The model's discriminative power assessed by Harrell's C statistic was 0.65. Fatigue score explained almost all the survival variability. CONCLUSION: HRQOL scores have prognostic value for mPA patients with good ECOG-PS. Moreover, the patient's fatigue, appetite loss, and self-perception of daily activities were more reliable prognostic indicators than clinical and laboratory variables. These HRQOL scores, especially the fatigue symptom, should be urgently included for prognostic assessment of mPA patients (with good ECOG-PS).


Assuntos
Adenocarcinoma/psicologia , Apetite/fisiologia , Fadiga/psicologia , Neoplasias Pancreáticas/psicologia , Qualidade de Vida/psicologia , Autoimagem , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Autorrelato , Inquéritos e Questionários , Neoplasias Pancreáticas
15.
JAMA ; 315(17): 1844-53, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27139057

RESUMO

IMPORTANCE: In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. OBJECTIVES: To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. DESIGN, SETTING, AND PARTICIPANTS: In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. INTERVENTIONS: In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. RESULTS: A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. CONCLUSIONS AND RELEVANCE: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00634725.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Gencitabina
16.
BMC Cancer ; 14: 441, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24929865

RESUMO

BACKGROUND: FOLFOX second-line treatment seems to be a validated option for patients with pancreatic cancer (PC) progressing after gemcitabine chemotherapy. However, other therapeutics strategy has developed in first-line therapy, as the FIRGEM phase II study that evaluated gemcitabine alone versus FOLFIRI.3 alternating with gemcitabine every two months. The present study assessed the efficacy and safety of FOLFOX after failure of the first-line therapy used in the FIRGEM study. METHODS: In this prospective observational cohort study, we analysed all consecutive patients who received second-line chemotherapy with FOLFOX among 98 patients with metastatic PC included in the FIRGEM study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method. RESULTS: Among 46 patients who received second-line chemotherapy, 27 patients (male, 55%; median age, 61 years; performance status (PS) 0-1, 44%) were treated with FOLFOX after progression to first-line gemcitabine alone (n = 20) or FOLFIRI.3 alternating with gemcitabine (n = 7). Grade 3 toxicity was observed in 33% of patients (no grade 4 toxicity). At the end of follow-up, all patients had progressed and 25 had died. No objective response was observed, and disease control rate was 36%. Median PFS and OS were 1.7 and 4.3 months, respectively. In multivariate analysis, PS was the only independent prognostic factor. For patients PS 0-1 versus 2-3, median PFS was 3.0 versus 1.2 months (log rank, p = 0.002), and median OS was 5.9 versus 2.6 months (log rank, p = 0.001). CONCLUSIONS: This study suggests that FOLFOX second-line therapy offered interesting efficacy results with an acceptable toxicity profile in metastatic PC patients with a good PS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Resultado do Tratamento
17.
J Clin Oncol ; 42(9): 1067-1076, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37963313

RESUMO

PURPOSE: GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS: Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS: Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION: This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Desoxicitidina/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Estudos Retrospectivos , Fluoruracila/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , RNA/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
18.
Artigo em Inglês | MEDLINE | ID: mdl-39341700

RESUMO

BACKGROUND: Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies. METHODS: COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).

19.
Radiother Oncol ; 193: 110144, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38341097

RESUMO

BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Idoso , Humanos , Qualidade de Vida , Avaliação Geriátrica , Terapia Neoadjuvante/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Retais/patologia , Segunda Neoplasia Primária/etiologia , Estadiamento de Neoplasias
20.
JAMA Oncol ; 10(6): 709-717, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573643

RESUMO

Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and Relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03959293.


Assuntos
Adenocarcinoma , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Junção Esofagogástrica , Fluoruracila , Leucovorina , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Idoso , Junção Esofagogástrica/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Adulto , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Intervalo Livre de Progressão
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