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1.
Int J Cancer ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749145

RESUMO

Biochemical recurrence (BCR) occurs in up to 40% of prostate cancer patients after prostatectomy. In this study, we performed an immune monitoring study in 20 prostate cancer patients with BCR previously treated with metronomic cyclophosphamide (mCTX). We observed a decrease of regulatory T cells (Tregs) from 2 months and this was more pronounced after 6 months of mCTX treatment. This drop of Tregs was associated with increased level of activated HLADR+ CD45R0+ T cells in peripheral blood. Furthermore, a reactivation of Th1 polarized anti-PSA T cell response was detected in BCR patients treated with mCTX. However, dendritic cell subsets counts and activation were not influenced by the treatment. In clinical setting, we found that PSA level control was observed in 82% (9/11) of patients with a significant diminution of Tregs after mCTX compared to 33% (3/9) in patients without Tregs decrease. In addition, 30% (6/20) of patients previously treated with mCTX remained free for androgen deprivation therapy. In conclusion, Tregs diminution and immune activation associated with PSA level control occurred after mCTX in prostate cancer patients with BCR. This article is protected by copyright. All rights reserved.

2.
Bull Cancer ; 106(10): 903-914, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31495441

RESUMO

Germ-cell tumors are the most common solid tumors in young men. The follow-up of these patients is very important in their management. In stage I testicular cancer, surveillance is the standard for low-risk disease. In addition to the early detection of relapse, follow-up should be directed towards prevention, detection and treatment of late toxicity, and secondary malignancies. Follow up consists in physical examination, laboratory analysis and radiological imaging. Recently, guidelines recommend risk-adapted surveillance strategy, with a reduction of CT scans numbers, due to the recognition of the risk of ionizing radiation exposure. However, efforts to maintain adequate compliance with follow up are required.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Embrionárias de Células Germinativas/prevenção & controle , Segunda Neoplasia Primária/diagnóstico , Neoplasias Testiculares/prevenção & controle , Adulto , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/prevenção & controle , Cooperação do Paciente , Exposição à Radiação/prevenção & controle , Prevenção Secundária , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
Bull Cancer ; 106(10): 915-922, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31126677

RESUMO

GOAL: Long-term evaluation of the incidence of sexual dysfunction from patients who were treated by orchidectomy, chemotherapy, and retroperitoneal lymphadenectomy for testicular cancer. METHODS: In 2018, patients who were treated in two academic hospitals by orchiectomy, chemotherapy, and retroperitoneal lymphadenectomy, and were in complete remission, were included. The patients included in this study filled the survey, which covered aspects of their sexuality (the Male Sexual Health Questionnaire) and answered additional questions, which evaluated psychological impact and modification of their sexuality since the management of their cancer. RESULTS: Twenty patients have been included, 70% of the patients treated for non-seminomatous germ cell tumor. Mean age was 36.4years±12.1 and the average duration of follow-up was 59months±34. Sexual dysfunction was found in 50% of the patients. Only 10% of the patients could preserve satisfying sexual activity during their treatment. Since the end of their treatment, 16%, 21% and 37% of patients respectively declared high libido loss, lower tumescent erections and persistence of anejaculation. In the end, nearly 70% of these patients wished a dedicated consultation with an urologist with subspecialty in andrology, in order to obtain further information during their care course. DISCUSSION: These patients have shown multicomponent sexual dysfunction. They could benefit from a new healthcare pathway implying early involvement of andrologist network.


Assuntos
Antineoplásicos/administração & dosagem , Excisão de Linfonodo/efeitos adversos , Orquiectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Disfunções Sexuais Fisiológicas/etiologia , Neoplasias Testiculares/terapia , Adulto , Andrologia , Coito , Ejaculação , Humanos , Libido , Masculino , Neoplasias Embrionárias de Células Germinativas/terapia , Ereção Peniana/fisiologia , Complicações Pós-Operatórias/epidemiologia , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Psicogênicas/etiologia
5.
Health Qual Life Outcomes ; 17(1): 25, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717745

RESUMO

BACKGROUND: Two main therapies, pazopanib and sunitinib, are used in the first-line setting for metastatic renal cell carcinoma (mRCC). These two tyrosine kinase inhibitors (TKI) are equally effective in terms of survival; however, they frequently induce adverse events. In this setting, Health-Related Quality of life (HRQoL) is a key element in the choice between these two treatments and the evaluation of treatment effectiveness. It could be of interest to evaluate HRQoL in daily clinical practice to aid adequate therapy choice and management. Currently, the development of information and communication technology may allow HRQoL monitoring in routine practice. The objective of the QUANARIE study is to evaluate the use of HRQoL assessment in daily clinical practice for patients with mRCC treated with TKI using electronic patient-reported outcomes (e-PRO). The present article describes the key elements of the study protocol. METHODS: The QUANARIE study is an interventional, prospective, multicentre trial. Patients diagnosed with mRCC initiating sunitinib or pazopanib treatment will be invited to complete the EORTC QLQ-C30 questionnaire, nine additional questions from the EORTC items library, and the EuroQoL EQ-5D, prior to each visit with the physician. Questionnaires will be completed by patients using tablets and/or computer terminals via the e-PRO software. The physician will have real-time access to a visual summary of the HRQoL evaluation. The primary objective is to assess the proportion of patients having good compliance with Routine Electronic Monitoring of HRQoL (REMOQOL) during the first 12 months. Physicians' satisfaction with REMOQOL will be assessed as a secondary objective. We hypothesise that 80% of patients having good compliance with REMOQOL would be meaningful. A sample size of 56 patients would be needed. DISCUSSION: The results of this study will show whether REMOQOL is feasible on a large scale and whether patients are receptive to this new practice. This study will also determine how real-time multidimensional evaluation of patient perception can help physicians in their daily practice and how they used it in conjunction with other clinical information to manage patient care. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT03062410 ; First Posted: February 23, 2017; Last Update Posted: August 9, 2017.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/psicologia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/psicologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
6.
Eur J Cancer ; 108: 33-40, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30616146

RESUMO

BACKGROUND: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. METHODS: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. RESULTS: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3. CONCLUSION: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30502046

RESUMO

BACKGROUND: Targeted therapies have transformed the treatment of metastatic clear-cell renal cell carcinoma (mccRCC). Despite the importance of mccRCC, studies on its economic burden in daily practice are sparse. The purpose of this retrospective study was to evaluate cost of illness for 224 patients with mccRCC included in the cohort published by Thiery-Vuillemin et al (Factors influencing overall survival for patients with metastatic clear-cell renal cell-carcinoma in daily practice. Clin Genitourin Cancer 2018; 16:e297-305), and then to determine the explanatory factors of cost of illness. PATIENTS AND METHODS: The study was performed from the French Public Healthcare System perspective with lifetime horizon. Only direct medical costs were included. Multiple linear regression was used to search for explanatory factors of cost of illness. The robustness of results was assessed. RESULTS: The mean cost of illness was estimated at €71,185 ± 52,683. Outpatient/inpatient treatment and hospitalization represented 76.0% and 19.7% of this cost, respectively. After adjustment, 5 explanatory factors were identified: time of disease control for the metastatic first-line treatment ≥6 months, number of lines of treatment >2, nephrectomy at metastatic stage, lack of metastases at presentation, and age at metastatic diagnosis younger than 65 years. Individually, they increased cost of illness by 128%, 95%, 53%, 53%, and 23%, respectively. CONCLUSION: Although it is difficult to transpose our economic evaluation results to those obtained in other countries, it should be noted that our findings were consistent with them and robust. To our knowledge, our study was the first to accurately identify explanatory factors of cost of illness. Identifying them could enable us to predict the budgetary effect on a regional level of managing patients who began their first-line treatment with a targeted therapy.

8.
Trials ; 19(1): 221, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29650037

RESUMO

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved in the first-line metastatic renal cell carcinoma (MRCC) setting at the dose of 50 mg daily for 4 weeks followed by a pause of 2 weeks. Due to toxicity, this standard schedule (50 mg daily 4/2) can induce up to 50% of sunitinib dose modification (reduction and/or interruption). The current recommendation in such case is to reduce the dose to 37.5 mg per day (standard schedule 4/2). Recent data highlight an alternative schedule: 2 weeks of treatment followed by 1 week of pause (experimental schedule 2/1). The SURF trial is set up to evaluate prospectively experimental schedule 2/1 when toxicity occurs. This article displays the key elements of the study protocol. METHODS/DESIGN: SURF [NCT02689167] is a prospective, randomized, open-label phase IIb study. Patients are included at sunitinib initiation while receiving standard schedule 4/2 (50 mg daily) according to the marketing authorization indication. When a dose adjustment of sunitinib is required, patients are randomized between standard schedule 4/2 (37.5 mg daily) and experimental schedule 2/1 (50 mg daily). Key eligibility criteria are the following: patients with locally advanced inoperable or MRCC who are starting first-line treatment with sunitinib, with histologically or cytologically confirmed renal cancer clear cell variant or with a clear cell component, and with Karnofsky performance status ≥70%. The primary objective is to assess the median duration of sunitinib treatment (DOT) in each group. The key secondary objectives are progression-free survival, overall survival, time to randomization, objective response rate, safety, sunitinib dose intensity, health-related quality of life, and the description of main drivers triggering randomization. We hypothesized that experimental schedule 2/1 would result in an improvement in median DOT from 6 to 8.5 months. It was estimated that 112 patients would be needed in each arm during 24 months. In order to take into account the possibility of treatment discontinuation before randomization, 248 patients are necessary. DISCUSSION: The SURF trial is asking a pragmatic question adapted to the current practice on what is the best way to adapt sunitinib when treatment-related adverse events occur. The results of the SURF trial will bring high-value data to support the use of an alternative schedule in sunitinib treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02689167 . Registered on 26 February 2016.

9.
World J Urol ; 36(3): 427-433, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29230496

RESUMO

OBJECTIVE: To compare the oncological outcomes of testicle-sparing surgery (TSS) and radical orchiectomy (RO) in patients with Leydig cell tumor (LCT) of the testis. PATIENTS AND METHODS: A multicenter retrospective clinical study was conducted in 12 centers in France. All the patients with histologically proven LCT were included and analyzed according to treatment (organ-sparing surgery or radical orchiectomy). Patients underwent preoperative clinical, biological and imaging assessment. Demographic, clinical, and pathological variables were collected at baseline and compared between groups according to surgical treatment. Follow-up was calculated using the reverse Kaplan-Meier estimation and was updated at the end of 2015. RESULTS: Between 1986 and 2014, 56 patients presented with LCT were identified and included in the study. Twenty-one patients (37.5%) underwent TSS and 35 (62.5%) RO. Demographics and tumor characteristics were not significantly different between the groups. Median follow-up was 62 months after TSS, but only 35 months after RO. Two patients (9.5%) developed local recurrence 15 and 34 months after TSS and underwent secondary RO. No local recurrence or metastasis was observed after complementary treatment. No recurrence was observed after RO. Disease-free survival did not differ between the groups (95.2% in TSS versus 77.1% in the RO group, p = 0.23). No patient died in the TSS group, but three patients (8.6%) in the RO group died from other diseases without evidence of relapse. One patient (4.8%) in the TSS group versus five (14.3%) in the RO group were lost to follow-up. CONCLUSION: Long-term follow-up suggests that testicle-sparing surgery does not compromise relapse-free survival in the treatment of Leydig cell tumor of the testis.


Assuntos
Tumor de Células de Leydig/cirurgia , Orquiectomia/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias Testiculares/cirurgia , Adulto , Intervalo Livre de Doença , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Tumor de Células de Leydig/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Testículo
10.
Clin Genitourin Cancer ; 16(2): e297-e305, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29066073

RESUMO

PURPOSE: To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies. PATIENTS AND METHODS: Two hundred twenty-four consecutive patients with histologically confirmed mccRCC who received targeted therapy on first-line treatment between January 2007 and March 2015 were included. The primary end point was OS for metastatic first-line or second-line treatment. An analysis of prognostic factors of long survival was performed using a 2-step approach: univariate, then multivariate analysis. RESULTS: Median OS [95% confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were identified in first-line treatment: Memorial Sloan Kettering Cancer Center (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval] = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10-4), metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95% confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different prognostic factors predicted long survival: toxicity for first-line treatment discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10-4), duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10-4), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936 [0.607-1.443], respectively, P = .02). CONCLUSION: These real-life data confirm the positive impact of targeted therapy in the mccRCC setting. Moreover, it emphasizes the importance of considering many factors in order to better estimate prognosis in patient pretreated with systemic therapy.

12.
Cancer Chemother Pharmacol ; 79(6): 1273-1276, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28451830

RESUMO

Axitinib is approved with indication in patients with advanced renal cell carcinoma (RCC). Due to the localization of this cancer, physicians sometimes have to deal with hemodialyzed patients. Data exploring hemodialysis (HD) impact on axitinib pharmacokinetic (PK) or safety are lacking. To date, no data have been published on that problematic. This is the first publication discussing the assessment of axitinib PK for a patient undergoing HD. Our results suggest that there is no influence of HD on axitinib blood concentration. Interestingly, the membranes used are common and represent around 90% of the membranes used in routine for HD. Our data are also reassuring both from activity and from safety perspectives. In that case, axitinib administered at a dose of 6 mg twice a day was well tolerated and allowed 12 months of disease control. These results are in line with previous publications discussing other anti-angiogenic tyrosine kinase inhibitors pharmacokinetics, safety and activity among patients with metastatic RCC undergoing hemodialysis.


Assuntos
Inibidores da Angiogênese/farmacocinética , Imidazóis/farmacocinética , Indazóis/farmacocinética , Inibidores de Proteínas Quinases/farmacocinética , Diálise Renal , Inibidores da Angiogênese/uso terapêutico , Axitinibe , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Intervalo Livre de Doença , Humanos , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Masculino , Membranas Artificiais , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
13.
Rev Infirm ; 66(227): 36-37, 2017 Jan.
Artigo em Francês | MEDLINE | ID: mdl-28048994

RESUMO

The measurement of the quality of life in terms of health of people undergoing treatment for cancer is developing. This new indicator focusing on patients' personal experience is combined with standard criteria relating to their tumours. The data are also a factor in the prognosis of overall survival. A team of researchers at Besançon university hospital shares its experience.


Assuntos
Neoplasias/diagnóstico , Qualidade de Vida , Humanos , Informática Médica/organização & administração , Informática Médica/normas , Neoplasias/mortalidade , Neoplasias/enfermagem , Padrões de Prática em Enfermagem/normas
14.
Bull Cancer ; 103(10): 849-860, 2016 Oct.
Artigo em Francês | MEDLINE | ID: mdl-27692731

RESUMO

INTRODUCTION: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain. METHODS: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included. RESULTS: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life. CONCLUSION: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate.


Assuntos
Analgésicos/uso terapêutico , Neoplasias da Mama/complicações , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Manejo da Dor , Neoplasias da Próstata/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Dor Crônica/etiologia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Neuralgia/etiologia , Medição da Dor , Satisfação do Paciente , Prevalência , Estudos Prospectivos , Qualidade de Vida , Autorrelato , Inquéritos e Questionários
15.
Clin Med Insights Oncol ; 10: 77-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27559302

RESUMO

INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by six cycles of maintenance temozolomide (150-200 mg/m(2), five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients.

16.
Med Oncol ; 33(8): 89, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27400698

RESUMO

After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Ciclofosfamida/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/mortalidade , Administração Metronômica , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade
17.
Cancer Res ; 76(14): 4100-12, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27197194

RESUMO

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes(+)CD8(+) T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs-exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100-12. ©2016 AACR.


Assuntos
Carcinoma de Células Renais/imunologia , Everolimo/farmacologia , Imunossupressores/farmacologia , Neoplasias Renais/imunologia , Linfócitos T/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Interferon gama/biossíntese , Interleucina-2/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Telomerase/imunologia , Células Th1/imunologia
18.
J Natl Cancer Inst ; 108(7)2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26839356

RESUMO

BACKGROUND: Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02). CONCLUSION: This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias Colorretais , Instabilidade de Microssatélites , Síndromes Neoplásicas Hereditárias , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Mutação em Linhagem Germinativa , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
19.
PLoS One ; 10(5): e0125350, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26010884

RESUMO

BACKGROUND: A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study. METHODS: HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS. RESULTS: 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21-0.59]) and pain (0.50 [0.31-0.81]) than those of Arm 1. CONCLUSION: Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients' characteristics. TRIAL REGISTRATION INFORMATION: Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Qualidade de Vida/psicologia , Adulto , Idoso , Desoxicitidina/uso terapêutico , Feminino , Nível de Saúde , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/psicologia , Neoplasias Hepáticas/secundário , Estudos Longitudinais , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/psicologia , Projetos de Pesquisa , Inquéritos e Questionários , Análise de Sobrevida
20.
Mol Clin Oncol ; 3(6): 1208-1212, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26807222

RESUMO

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m2 intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9-4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06-12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy.

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