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1.
Ann Oncol ; 35(3): 248-266, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307807

RESUMO

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.


Assuntos
Oncologia , Neoplasias Ovarianas , Humanos , Feminino , Sociedades Médicas , Espanha , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Biologia Molecular
2.
J Gynecol Obstet Hum Reprod ; 48(6): 379-386, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936025

RESUMO

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).


Assuntos
Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Neoplasias das Tubas Uterinas/tratamento farmacológico , Feminino , Preservação da Fertilidade , França , Humanos , Hipertermia Induzida , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico
3.
J Gynecol Obstet Hum Reprod ; 48(6): 369-378, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936027

RESUMO

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).


Assuntos
Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Biomarcadores Tumorais/sangue , Neoplasias das Tubas Uterinas/patologia , Feminino , França , Humanos , Laparoscopia , Imageamento por Ressonância Magnética , Procedimentos Cirúrgicos Minimamente Invasivos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Assistência Perioperatória , Neoplasias Peritoneais/patologia , Tomografia Computadorizada por Raios X
4.
Eur J Obstet Gynecol Reprod Biol ; 236: 214-223, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30905627

RESUMO

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).


Assuntos
Carcinoma/terapia , Neoplasias das Tubas Uterinas/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Antineoplásicos/uso terapêutico , Carcinoma/diagnóstico , Carcinoma/patologia , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Feminino , França , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia
5.
Gynecol Obstet Fertil Senol ; 47(2): 111-119, 2019 02.
Artigo em Francês | MEDLINE | ID: mdl-30704955

RESUMO

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).


Assuntos
Carcinoma Epitelial do Ovário/terapia , Neoplasias Ovarianas/terapia , Fatores Etários , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Continuidade da Assistência ao Paciente , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/terapia , Feminino , Preservação da Fertilidade , França , Humanos , Hipertermia Induzida , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Sociedades Médicas
6.
Gynecol Obstet Fertil Senol ; 47(2): 238-249, 2019 02.
Artigo em Francês | MEDLINE | ID: mdl-30712964

RESUMO

In ovarian, tubal and primary peritoneal cancers, older adults have an over-mortality due to more aggressive disease (NP4), surgical and chemotherapy under treatment (NP4) and co-morbidities (NP4). Older age is at higher risk for postoperative morbidity and mortality (NP4). Surgery is more often incomplete in this elderly population (NP4). Older age is a risk factor for lower dose intensity in adjuvant chemotherapy (NP4) and incomplete chemotherapy (NP4). Nevertheless, the benefit of a complete surgery remains identical to that of the younger population (NP2). Preoperative functional assessment identifies patients at risk for postoperative complications (NP4). The perioperative risk depends on three variables, the ASA score, the age and the complexity score of the surgery (NP4). It is recommended to perform cytoreduction surgery in an expert centre (grade C) and on the basis of geriatric expertise analysing functional and physical performance (grade C). The benefit/risk balance of surgery should be assessed on a case-by-case basis for the most at-risk (NP4) populations defined by: (i) age≥80 years, especially if albuminemia≤37g/L; (ii) age≥75 years and FIGO stage IV; (iii) age≥75 years, stage FIGO III and≥1 comorbidity. A comprehensive geriatric assessment is recommended prior to the management of an elderly person with primary ovarian, tubal or peritoneal cancer (grade C). The GVS (Geriatric Vulnerability Score) is used to identify vulnerable elderly patients (NP2). In fit elderly patients, it is recommended to perform intravenous chemotherapy identical to that of younger patients (ie platinum-based dual therapy) (grade B). In vulnerable elderly patients, various adapted chemotherapy regimens have been prospectively evaluated in non-comparative trials, and seem feasible considering specific and nonspecific toxicities: carboplatin monotherapy (NP2), carboplatin AUC2+paclitaxel 60mg/m2 3 weeks/4 (NP2), carboplatin AUC 4-5+paclitaxel 135mg/m2/3 weeks (NP2), carboplatin AUC5/3 weeks+paclitaxel 60mg/m2/week (NP3). In the absence of comparative data, no recommendation can be made in this population. Primary chemotherapy decreases the complexity of the surgical procedure and perioperative morbidity and mortality during interval surgery (NP1). It should be considered after 70 years in cases of comorbidities and/or peritoneal carcinomatosis sufficient for complex initial surgery (NP4).


Assuntos
Carcinoma Epitelial do Ovário/terapia , Neoplasias Ovarianas/terapia , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Comorbidade , Procedimentos Cirúrgicos de Citorredução , Feminino , França , Humanos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Complicações Pós-Operatórias/mortalidade , Prognóstico , Medição de Risco , Sociedades Médicas
7.
Gynecol Obstet Fertil Senol ; 47(2): 100-110, 2019 02.
Artigo em Francês | MEDLINE | ID: mdl-30686724

RESUMO

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).


Assuntos
Carcinoma Epitelial do Ovário/terapia , Neoplasias Ovarianas/terapia , Algoritmos , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Antígeno Ca-125/análise , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/patologia , Terapia Combinada , DNA de Neoplasias/sangue , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/terapia , Feminino , França , Humanos , Laparoscopia , Excisão de Linfonodo , Proteínas de Membrana/análise , Metástase Neoplásica/terapia , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Assistência Perioperatória , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Proteínas/análise , Sociedades Médicas , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos
8.
Ann Oncol ; 28(10): 2606-2611, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961850

RESUMO

BACKGROUND: Physicians need well-addressed clinical trials assessing benefits and harm of treatments to avoid under-treatment or over-treatment of elderly patients. The main objectives of this report were to present an overview of end points used in clinical trials dedicated to elderly patients; and to assess the evolution in chosen end points before and after the creation of the International Society of Geriatric Oncology in the early 2000s. PATIENTS AND METHODS: All phases I, II and III trials dedicated to the treatment of cancer among elderly patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. All phase III clinical trials assessing cancer treatments among adults in the same periods were also reviewed to identify subgroup analyses of elderly patients among these trials. RESULTS: Among phase III trials dedicated to elderly patients, overall survival was a common primary end point. Interestingly, tumor centered end points were very common in the first time period and very uncommon in the second time period, whereas composite end points were very uncommon in the first time period but very common in the second time period. Concerningly, disease-specific survival was very infrequently reported in dedicated clinical trials of elderly patients despite their importance in evaluating competing risk of death from non-oncology causes. The use of patient-reported outcomes (PROs) as a primary end point remained very uncommon but the reporting of PROs as a secondary end point tended to increase in the second time period, from 19% to 33% (P = 0.10). Functional status was infrequently reported. CONCLUSION: During the past decade, the use of clinically meaningful end points such as PROs and functional status in elderly patients remained moderate. Yet, the use of PROs as a secondary end point tended to increase between the two time periods.


Assuntos
Ensaios Clínicos como Assunto/métodos , Neoplasias/terapia , Fatores Etários , Idoso , Ensaios Clínicos Fase III como Assunto/métodos , Determinação de Ponto Final , Avaliação Geriátrica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
9.
Ann Oncol ; 27(9): 1799-804, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27358382

RESUMO

BACKGROUND: Physicians need clinical trials assessing benefits and harms of treatments to avoid under-treatment or over-treatment of elderly patients. The main objectives of this report were to examine how data regarding elderly oncology patients were presented in medical literature; and to assess the evolution of this presentation between two time periods. PATIENTS AND METHODS: All phases I, II and III trials dedicated to the treatment of cancer among elderly patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. All phase III clinical trials assessing cancer treatments among adults in the same periods were also reviewed to evaluate potential subgroup analyses in elderly patients in these studies. Key characteristics of interest were extracted by two investigators before descriptive and comparative analyses were undertaken. RESULTS: A total of 1084 trials were included: 366 and 718 from the first and second time period, respectively. Twenty-seven and 193 of these trials were phase I and II trials dedicated to elderly or frail patients, respectively. A large proportion of phase III trials published between 2011 and 2014 reported at least one analysis dedicated to elderly patients (46.7%) versus 19.3% during the first time period. The use of subgroup analyses of elderly patients in phase III trials was the most frequent source of information. Subgroup analyses were more frequent among trials with industrial funding, trials published in high impact factor journal, intercontinental trials and trials with large sample size. The age threshold defining the elderly subgroup increased over time. CONCLUSION: Elderly patients have become a topic of interest during the past decade. However, data available are mostly extracted from subgroup analyses, which can only be regarded as preliminary evidence.


Assuntos
Ensaios Clínicos como Assunto , Neoplasias/tratamento farmacológico , Seleção de Pacientes , Adulto , Idoso , Humanos , Oncologia , Neoplasias/epidemiologia
10.
Ann Oncol ; 24(11): 2808-13, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24061628

RESUMO

BACKGROUND: Two previous GINECO elderly specific studies in advanced ovarian cancer (AOC) patients highlighted the prognostic value of geriatric covariates for overall survival (OS). PATIENTS AND METHODS: This open-label prospective trial was designed to identify the impact of geriatric covariates on OS in AOC patients ≥70 years treated with first-line carboplatin. RESULTS: Geriatric covariates of the 111 patients included median age 79 years (≥80 years: 41%); performance status (PS) ≥2: 47%; ≥3 major comorbidities: 24%; ≥4 comedications: 68%; activities of daily living (ADL) score <6: 55%; instrumental activities of daily living (IADL) score <25: 69%; Hospital Anxiety and Depression Scale (HADS) >14: 37%. The median OS was 17.4 months. Overall, 74% of patients completed the six planned chemotherapy cycles. Grade 3-4 haematological toxic effects were frequent (50%) but manageable. Grade 3-4 non-haematological toxicities included fatigue (15%), anorexia (12%), infections (9%) and thrombosis (2%). A survival score = exp(0.327*GVS) was developed, where the geriatric vulnerability score (GVS) is the sum of the following (each assigned a value of one): albuminaemia <35 g/l; ADL score <6; IADL score <25; lymphopaenia <1 G/l; and HADS >14. With a cut-off ≥3, GVS discriminated two groups with significantly different OS, treatment completion, severe adverse events and unplanned hospital admissions rates. CONCLUSIONS: The GVS is a valuable tool for identifying vulnerable patients when treating an elderly AOC population.


Assuntos
Carboplatina/administração & dosagem , Avaliação Geriátrica , Neoplasias Ovarianas/tratamento farmacológico , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Carboplatina/efeitos adversos , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
11.
Eur J Cancer ; 49(13): 2806-14, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23735702

RESUMO

BACKGROUND: Metastatic breast cancer chemotherapy in the elderly is considered effective in carefully selected patients, but there is little data regarding its effect in vulnerable patients. METHODS: We evaluated tumour response (primary endpoint), feasibility and outcomes after six courses of an adapted dose of pegylated liposomal doxorubicin (PLD) (40 mg/m(2) every 28 days) as first-line chemotherapy for hormone-resistant MBC. RESULTS: Of 60 patients >70 years (median 77 years), 15% had performance status ≥2 and 73% had visceral metastases. Geriatric assessment included: ≥2 comorbidities, 42%; ≥1 deficiency in Activities of Daily Living (ADL), 10% and Instrumental ADL (IADL), 82%; living in residential homes, 12%; albumin <35 g/L, 17%; body mass index (BMI) <21, 20%; depression, 17%; and lymphocytes ≤1 × 10(3)/mm(3), 27%. Complete response, partial response and stable disease were observed in 5%, 15% and 60%, respectively, but only 48% completed six cycles. Treatment discontinuations were mostly due to disease progression (18%) and non-haematological (NH) toxicities (22%). Eight patients died during treatment (three possibly related to PLD), and 15 had unplanned hospital admissions. Exploratory analyses to identify geriatric covariates associated with treatment outcomes revealed severe haematological toxicities significantly correlated with lymphocytes ≤1 × 10(3)/mm(3). NH toxicities correlated with age ≥80 years and living in residential homes. Progression-free survival (median 6.1 months) decreased with age, deficiency in IADL, cardiac dysfunction and living in residential homes. Overall survival (median 15.7 months) also decreased with living in residential homes. CONCLUSION: Despite manageable haematological toxicities and expected response rates, PLD feasibility was poor in unselected elderly patients.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/análogos & derivados , Polietilenoglicóis/uso terapêutico , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/secundário , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , França , Avaliação Geriátrica , Cardiopatias/complicações , Instituição de Longa Permanência para Idosos , Humanos , Estimativa de Kaplan-Meier , Análise Multivariada , Casas de Saúde , Razão de Chances , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
13.
Br J Cancer ; 107(4): 598-603, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22790797

RESUMO

BACKGROUND: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours. METHODS: Patients received intravenous aflibercept 4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination. RESULTS: During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs. CONCLUSION: Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Receptores de Fatores de Crescimento do Endotélio Vascular
14.
Eur J Cancer ; 46(13): 2389-98, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20732287

RESUMO

BACKGROUND: Although international guidelines have standardised conditions for G-CSF administration, real practice seems to vary. PATIENTS AND METHODS: A large survey was undertaken in France following a three-step method. Data concerning 990 patients in seven main indications were collected prospectively and analysed for their compliance with international guidelines. RESULTS: G-CSF prescription rate varied from 81% in non-Hodgkin lymphoma (NHL), 55% in ovarian, 44% in breast and 21% in colorectal cancer. The main criteria for G-CSF administration were a chemotherapy regimen with a high risk of neutropaenia (65%) and associated risk factors (51%). Public hospital practitioners prescribed G-CSF more frequently as primary prophylaxis, whereas prescriptions of recently graduated practitioners (or=16 years) were often proposed as secondary prophylaxis or as G-CSF therapy, i.e. during ongoing neutropaenia. In prophylactic settings, administration schedules were highly variable depending on molecules, with a first day of administration between days 1 and 3 after chemotherapy in 66%, but before the end of the chemotherapy infusion in 13% of the cases. Concerning lenograstim (38% of prescriptions) and filgrastim (20%), the mean treatment duration was 5.5 days, significantly shorter than in 1999 (7.8 days). CONCLUSION: G-CSF prescription was mainly in compliance with international guidelines. However, some too early administrations during chemotherapy are at risk of increased myelosuppression and should be more clearly disadvised in next international guidelines.


Assuntos
Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Idoso , Atitude do Pessoal de Saúde , Institutos de Câncer/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Filgrastim , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prática Profissional/tendências , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico
15.
Ann Oncol ; 21(12): 2377-2381, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20494964

RESUMO

BACKGROUND: Advanced mucinous epithelial ovarian carcinoma (mEOC) has been associated with a worse prognosis than the more common serous epithelial ovarian carcinomas (sEOC), but it remains unclear whether this observation reflects a more aggressive clinical presentation and/or chemoresistance. PATIENTS AND METHODS: Data from four randomized phase III and one phase II advanced epithelial ovarian carcinoma (EOC) first-line clinical trials were retrospectively collected, yielding 1118 patients with advanced EOC (International Federation of Gynecology and Obstetrics stages IIB-IV), 85% of whom were treated with paclitaxel (Taxol)-carboplatin-based chemotherapy. RESULTS: Based on 786 patients with sEOC and 54 (5%) with mEOC, peritoneal carcinomatosis were more limited in mEOC, which was more frequently stages IIB-IIIB (32% versus 19%, P = 0.001) and had more frequently macroscopic complete resection after initial surgery (50% of stages II-III versus 30%, P = 0.02). In contrast, visceral metastases (stage IV) were more frequent in mEOC (30% versus 15%, P = 0.004). mEOC had a lower response rate to carboplatin-paclitaxel, and shorter progression-free and overall survival rates, for both stage IV and optimally debulked stages II-III patients. CONCLUSIONS: Advanced mEOC appears to be highly chemoresistant and complete resection of peritoneal metastases is unable to reverse its poor prognosis. New therapeutic options are needed.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Platina/administração & dosagem , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/tratamento farmacológico , Cistadenocarcinoma Mucinoso/patologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/efeitos adversos , Platina/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
16.
Ann Oncol ; 20(4): 615-20, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19254941

RESUMO

Aromatase inhibitors (AIs) are well established in the treatment of metastatic hormone-sensitive breast cancer in postmenopausal women. Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing cancer risk in animal and human studies. In several preclinical studies, combination AI plus COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI exemestane and the COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic breast cancer settings. In general, combination therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All therapies were well tolerated. There appeared to be a beneficial impact on serum lipid levels for patients receiving combination therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with COX-2 inhibitors. In conclusion, AIs plus COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk-benefit ratio of combination therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/patologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Feminino , Humanos , Metástase Neoplásica , Resultado do Tratamento
17.
Breast Cancer Res Treat ; 116(3): 501-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19020973

RESUMO

The aim of this study was to evaluate antitumor effects of cyclooxygenase-2 inhibitors in breast carcinoma and their ability to act synergistically with aromatase inhibitors (AIs). Postmenopausal metastatic breast cancer patients without previous adjuvant AI treatment received exemestane 25 mg/days plus either celecoxib 400 mg twice daily or placebo. The primary endpoint was progression-free survival (PFS). This trial was prematurely terminated (N = 157 of 342 planned) after cardiovascular toxicity was reported in other celecoxib trials. Although no PFS difference was observed between the two arms (9.8 months for both, P = 0.72), a trend favoring celecoxib was observed in 60 tamoxifen-resistant patients (9.6 vs. 5.1 months; P = 0.14) and in 126 patients treated >or=3 months before study termination (12.2 vs. 9.8 months; P = 0.09). No severe adverse events were reported. Cyclooxygenase-2 inhibitors seemingly contribute to reverse endocrine resistance in breast cancer patients, although further study is necessary to allow development of a new therapeutic strategy.


Assuntos
Androstadienos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfonodos/patologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Doenças Cardiovasculares , Celecoxib , Quimioterapia Adjuvante , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Linfonodos/efeitos dos fármacos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/secundário , Placebos , Pós-Menopausa , Prognóstico , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/secundário , Taxa de Sobrevida , Resultado do Tratamento
18.
Cancer Radiother ; 12(6-7): 541-7, 2008 Nov.
Artigo em Francês | MEDLINE | ID: mdl-18838284

RESUMO

Cancer in the elderly represents a major public health topic and its importance will increase in the future because of increased life expectancy and ageing. Cancer prognosis is worse due to late diagnosis, frequent comorbidities and treatment often considered as suboptimal. Reference treatments were primarily validated for younger or selected elderly patients and experimental data collected on most vulnerable are rare. Oncogeriatrics development for 15 years made it possible to consider two fundamental aspects, which are the geriatric evaluation, from the most simple to the complete one, and the development of specific trials. In addition, a strong institutional policy allowed promotion, on the French national territory, of regional experiments thanks to Pilot Units of Oncogeriatrics Coordination (UPCOG). The question of the interest of a geriatric evaluation in radiotherapy is related mainly to the difficulties of tolerance and observance of this treatment, but also with its effectiveness and this review explores the main curative, adjuvant and palliative indications as well as research perspectives.


Assuntos
Envelhecimento/efeitos da radiação , Neoplasias/radioterapia , Radioterapia/métodos , Atividades Cotidianas , Idoso , Cognição , Humanos , Expectativa de Vida , Cuidados Paliativos , Seleção de Pacientes , Radioterapia Adjuvante/métodos
19.
Clin Oncol (R Coll Radiol) ; 20(5): 369-74, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18406583

RESUMO

AIMS: To determine the feasibility of radiotherapy-associated capecitabine, irinotecan and oxaliplatin administration at five dose levels for the treatment of locally advanced rectal cancer, with or without metastasis. PATIENTS AND METHODS: This was a bicentric phase I trial, including patients with locally advanced rectal cancer, with or without metastasis. Chemotherapy comprised capecitabine (1100, 1300 or 1500 mg/m2/day, every day), irinotecan (30, 40 or 50mg/m2, once per week for 6 weeks) with the addition of oxaliplatin (40 mg/m2 at level 4 or 50 mg/m2 at level 5, once per week for 6 weeks). Radiotherapy at 46 Gy plus a boost of 4 Gy was administered concomitantly. RESULTS: Twelve patients received four levels of dose. As a supplement to radiotherapy, the combination of capecitabine and irinotecan at the respective doses of 1500 mg/m2/day and 50 mg/m2/week was feasible and well tolerated. The addition of oxaliplatin to this combination provoked toxicity (grade 3/4 vomiting, diarrhoea) for two-thirds of the patients. CONCLUSION: A treatment associating radiotherapy (46 Gy+4 Gy) with concomitant chemotherapy comprising capecitabine (1500 mg/m2/day, every day) and irinotecan (50 mg/m2/week, for 5 weeks) was feasible and well tolerated. The addition of oxaliplatin to these doses was prohibitory to the continuation of treatment due to unacceptable toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Radioterapia Conformacional , Neoplasias Retais/patologia
20.
Ann Oncol ; 16(10): 1675-82, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16030029

RESUMO

BACKGROUND: Predictive factors of rituximab efficacy and its effect on the immune system are still not defined. PATIENTS AND METHODS: Three hundred and six patients with follicular or mantle cell lymphoma received four weekly doses of rituximab (induction) and no further treatment (arm A) or four more doses at 2-month intervals (arm B). RESULTS: Response rate to induction was 44%. Independent predictive factors for response were disease bulk <5 cm, follicular histology, normal hemoglobin and low lymphocyte count. Factors associated with event-free survival (EFS) were having responded to induction, having received not more than one line of therapy, Ann Arbor stage I-III, high lymphocyte count, disease bulk <5 cm, Fc-gamma receptor genotype VV and receiving prolonged treatment. B cells were suppressed by treatment but recovered after a median of 12 months in arm A and 18 months in arm B. The median IgM level after 1 year was normal in arm A but was decreased to 73% of baseline in arm B. We observed 24 serious adverse events, equally distributed between arms. Ten patients receiving induction only and six patients receiving prolonged treatment developed a second tumor. CONCLUSIONS: We defined the characteristics predicting response and EFS to rituximab. Prolonged treatment results in longer EFS at the cost of a longer reduction in B cell and IgM levels, but without additional clinical toxicity.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/imunologia , Anticorpos Monoclonais Murinos , Linfócitos B/efeitos dos fármacos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Imunoglobulina M/análise , Imunoglobulina M/efeitos dos fármacos , Contagem de Linfócitos , Linfoma Folicular , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Rituximab
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