Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
J Clin Pathol ; 75(1): 39-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33144356

RESUMO

AIMS: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1). METHODS: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed. RESULTS: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC. CONCLUSION: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.


Assuntos
Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores/metabolismo , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Análise Serial de Tecidos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
2.
Eur J Cancer ; 140: 140-146, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33091718

RESUMO

BACKGROUND: Patients with cancer are at increased risk of complicated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but it is still unclear if the risk of mortality is influenced by cancer type or ongoing anti-cancer treatments. An interesting debate concerning the potential relationship between androgen deprivation therapy (ADT) and SARS-CoV-2 infection has recently been opened in the case of prostate cancer (PC), and the aim of this multi-centre cohort study was to investigate the incidence and outcomes of SARS-CoV-2 infection in patients with metastatic castration-resistant prostrate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC who developed SARS-CoV-2 infection, and recorded their baseline clinical characteristics, their history of PC and SARS-CoV-2 infection, and their oncological status and treatment at the time of infection. The primary study end point was the death rate and the possible impact of the patients' PC-related history and treatments on mortality. RESULTS: Thirty-four of the 1433 patients with mCRPC attending the participating centres (2.3%) developed SARS-CoV-2 infection, 22 (64.7%) of whom were hospitalised. Most of the patients were symptomatic, the most frequent symptoms being fever (70.6%), dyspnoea (61.8%), cough (52.9%) and fatigue (38.2%). After a median follow-up of 21 days (interquartile range: 13-41), 13 patients had died (38.2%), 17 recovered (50.0%) and four (11.7%) were still infected. The number of treatments previously administered for mCRPC had a significant impact on mortality (p = 0.004). CONCLUSIONS: Our findings contribute additional data to the current debate concerning the postulated protective role of ADT, which seems to be less in patients with metastatic PC.


Assuntos
Betacoronavirus/isolamento & purificação , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/mortalidade , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Neoplasias Ósseas/virologia , COVID-19 , Terapia Combinada , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/virologia , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida
3.
Expert Rev Anticancer Ther ; 20(6): 491-501, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32479120

RESUMO

INTRODUCTION: The aim of this paper was to perform a narrative review of the literature on the available approaches in the treatment of two emerging subpopulations of metastatic renal cell carcinoma (mRCC) patients: the oligometastatic disease (less than 5 metastasis) and the oligoprogressive disease, defined as worsening in maximum 3-5 sites while all other tumor sites are controlled by systemic therapy. AREAS COVERED: We explore all possible approaches in these settings of patients: the role of local therapies, considering both surgical metastasectomy and/or ablative techniques, the efficacy of systemic therapies and the rationale behind active surveillance. We also discuss ongoing clinical trials in these settings. EXPERT OPINION: Two different strategies are emerging as the most promising for the approach to the oligometastatic/oligoprogressive mRCC patient: (1) the use of immunocheckpoint inhibitors following metastasectomy; (2) the use of stereotactic radiotherapy alone or combined with immunotherapy for oligometastatic disease. The lack of validated biomarkers of response in these mRCC patient subpopulations is opening the way to the employment of novel technologies. Among them, the use of artificial intelligence seems to be the candidate to contribute to precision oncology in patients with mRCC.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Inteligência Artificial , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Terapia Combinada , Progressão da Doença , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Imunoterapia/métodos , Neoplasias Renais/patologia , Metástase Neoplásica , Radiocirurgia/métodos
4.
Eur Urol Oncol ; 2(6): 699-707, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542243

RESUMO

BACKGROUND: In selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy. OBJECTIVE: To assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves. RESULTS AND LIMITATIONS: At a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20-not available [NA]) in the observation arm versus 21 mo (95% CI 11-NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm. CONCLUSIONS: This prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy. PATIENT SUMMARY: This article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/cirurgia , Metastasectomia/métodos , Sorafenibe/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sorafenibe/farmacologia
5.
Future Oncol ; 15(10): 1115-1123, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30887825

RESUMO

AIM: To evaluate activity of metronomic cyclophosphamide (mCTX) in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS & METHODS: We retrospectively evaluated a consecutive series of 74 mCRPC patients treated with at least one new agent after docetaxel failure, who received once-daily oral mCTX treatment at a fixed dose of 50 mg. RESULTS: The treatment was well tolerated. Sixteen percent of the patients experienced a major biochemical response. Median progression-free survival was 4.0 months, and median overall survival was 8.1 months. CONCLUSIONS: In the modern context of mCRPC, mCTX may represent a valuable and inexpensive alternative to new agents, which have shown similar activity in heavily pretreated patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/secundário , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Resultado do Tratamento
6.
Drugs R D ; 18(2): 163, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29808389

RESUMO

In the Original Publication of the article, In Introduction part, 7th line, the value "5-100nM" has been published incorrectly. The correct value should read as "Plasma concentration of 50-100ng/ml". In the Original Publication of the article, page 591, Table 2 has been published incorrectly. The corrected table is shown in the following page.

7.
Drugs R D ; 17(4): 585-596, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28895069

RESUMO

BACKGROUND: Standard treatment with sunitinib for patients with metastatic renal cancer provides an 'on-off' schedule (daily administration of a 50-mg capsule for 4 weeks, followed by a 2-week break; consecutive 6-week cycles). We developed an alternative intermittent schedule to reduce the toxicity and symptoms of tumor regrowth during the rest period and to allow prolonged continuation of therapy, maintaining dose intensity. OBJECTIVE: The objective of this study was to provide a retrospective evaluation of the feasibility, safety, and efficacy of an alternative schedule of sunitinib in patients who did not tolerate classical treatment. METHODS: Patients treated with the classical schedule with at least grade 2 toxicity or recurrence of symptoms during the rest period were switched to an alternative schedule (the same daily dose 5 consecutive days per week for 5 weeks and then the same daily dose on days 1, 3, and 5 in the sixth week; consecutive 6-week cycles). RESULTS: Twenty-five patients were enrolled. The median time from sunitinib initiation to schedule switch was 2.9 months. After the switch, the median therapy duration was 9.2 months. Rate of delay, corrected by cycle number, was 10% for both schedules. After the switch, 48.7% of patients obtained a toxicity reduction (hypertension -82%, stomatitis -71%, cutaneous toxicity -69%). A reduction in 'on-off symptoms' (-86%) was achieved. Overall response rate was 40% and the disease control rate was 80%. Median progression-free survival was 16.4 months and median overall survival was 41.3 months. CONCLUSIONS: Despite the small sample size and retrospective nature, we demonstrated the feasibility, safety, and efficacy of the alternative schedule, allowing prolonged treatment and better quality of life.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Pirróis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Indóis/efeitos adversos , Indóis/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Sunitinibe
8.
BMC Cancer ; 17(1): 493, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28724419

RESUMO

BACKGROUND: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice. METHODS: This was a retrospective multicenter study. Italian cancer centers were selected if, according to the Registry of the Italian Medicines Agency (AIFA), at least four patients had been treated with vinflunine between February 2011 and June 2014, after first- or second-line platinum-based chemotherapy. The primary objective was to test whether the efficacy measured by overall survival (OS) in the registration study could be confirmed in routine clinical practice. Multivariate analysis was carried out using Cox proportional hazard model. RESULTS: A total of 217 patients were treated in 28 Italian centers. Median age was 69 years (IQR 62-76) and 84% were male; Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥ 1 in 53% of patients. The median number of cycles was 4 (IQR 2-6); 29%, 35%, and 36% received an initial dose of 320 mg/m2, 280 mg/m2 or a lower dose, respectively. Median progression-free survival (PFS) and OS for the entire population was 3.2 months (2.6-3.7) and 8.1 months (6.3-8.9). A complete response was observed in six patients, partial response in 21, stable disease in 60, progressive disease in 108, with a disease control rate of 40%. Multivariate analysis showed that ECOG PS, number of metastatic sites and liver involvement were unfavorable prognostic factors for OS. Toxicity was mild, and grade 3-4 adverse effects were mainly: neutropenia (9%), anemia (6%), asthenia/fatigue (7%) and constipation (5%). CONCLUSIONS: In routine clinical practice the results obtained with VFL seem to be better than the results of the registration trial and reinforce evidence supporting its use after failure of a platinum-based chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Vimblastina/análogos & derivados , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição/secundário , Intervalo Livre de Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Platina/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias Urológicas/patologia , Urotélio/efeitos dos fármacos , Urotélio/patologia , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
9.
Future Oncol ; 12(4): 493-502, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26776493

RESUMO

AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Retratamento , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
10.
Clin Genitourin Cancer ; 14(1): 48-55, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26382222

RESUMO

UNLABELLED: Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population. BACKGROUND: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population. PATIENTS AND METHODS: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables. RESULTS: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature. CONCLUSION: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population.


Assuntos
Acetato de Abiraterona/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ensaios de Uso Compassivo , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
11.
Future Oncol ; 11(21): 2881-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26436290

RESUMO

BACKGROUND: The objective of this study was to analyze the impact of visceral metastases in castration-resistant prostate cancer (CRPC) treated with abiraterone. MATERIALS & METHODS: All CRPC patients received abiraterone 1000 mg daily plus prednisone 10 mg orally daily. Liver and lung metastases were considered as visceral metastases. RESULTS: Of 265 CRPC patients, 49 had visceral metastases. Results on progression-free survival were not significantly different in patients with or without visceral metastases. Conversely, the median overall survival between the two groups was 12.4 and 18.5 months (p = 0.01), respectively, and median overall survival of patients with liver-only disease versus other sites was 10.5 versus 18.5 months (p = 0.006), respectively. CONCLUSION: Visceral disease appears to be an important predictor of clinical outcome in CRPC patients treated with abiraterone.


Assuntos
Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Vísceras/patologia , Idoso , Idoso de 80 Anos ou mais , Androstenos/farmacologia , Antineoplásicos Hormonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
12.
Eur Urol ; 68(1): 147-53, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25457020

RESUMO

BACKGROUND: The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit. OBJECTIVE: To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis. RESULTS AND LIMITATIONS: We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences. CONCLUSIONS: We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy. PATIENT SUMMARY: It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Benzamidas , Estudos de Coortes , Intervalo Livre de Doença , Docetaxel , Humanos , Itália , Masculino , Análise Multivariada , Nitrilas , Feniltioidantoína/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento
13.
BJU Int ; 115(5): 764-71, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24988879

RESUMO

OBJECTIVE: To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals. RESULTS: We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3-4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases. CONCLUSIONS: Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.


Assuntos
Androstenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Antineoplásicos/uso terapêutico , Ensaios de Uso Compassivo , Docetaxel , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/uso terapêutico , Resultado do Tratamento
14.
Lung Cancer ; 80(1): 106-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23375402

RESUMO

Thymic carcinoma (TC) is a rare intrathoracic malignancy that it can be invasive and refractory to conventional treatment. Comprehensive genomic analysis evidenced a molecularly distinct subset of thymic carcinoma with high prevalence of c-kit mutation, which may behave as a gastrointestinal stromal tumor (GIST). Here, we present a case report of TC with c-Kit mutation, who has relapsed after exposure to multiple lines of combination chemotherapy, but he has shown an impressive and long lasting response to sunitinib after imatinib failure.


Assuntos
Indóis/uso terapêutico , Pirróis/uso terapêutico , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Mutação , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/uso terapêutico , Sunitinibe , Timoma/genética , Timoma/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/patologia , Falha de Tratamento , Resultado do Tratamento
15.
Tumori ; 98(1): 45-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22495701

RESUMO

AIMS AND BACKGROUND: The exact mechanism by which recombinant interleukine-2 and interferon-α modulate the immunological response, inducing long-term responses in metastatic renal cell carcinoma, is still not clear. The aim of the study was to analyze the modifications in peripheral blood lymphocytes during cycles of low-dose immunotherapy as a marker of the biological response to the treatment in 146 patients with renal cell carcinoma (advanced and localized disease). METHODS AND STUDY DESIGN: Peripheral blood lymphocytes were evaluated before and after every cycle of treatment. RESULTS: We found a statistically significant overall difference between pre- and post-cycle values (mean increase of 39%). The differences between pre- and post-cycle lymphocyte counts for each cycle were significant. Also, the post-cycle lymphocyte count of each cycle remained higher than the baseline value. Furthermore, pre-cycle lymphocyte counts of each cycle were still higher than the baseline value, with no difference between a pre-cycle lymphocyte mean value and the other one (except that between the first and second cycle). From the end of each cycle, but before starting the next one, the absolute value of lymphocytes fell on the average by 15-30%, concurring with the fact that, even starting from pre-cycle values higher than baseline, the immune system remains sensitive to chronically repeated stimulation by immunotherapy. We also found that non-metastatic patients had a higher number of peripheral blood lymphocytes than metastatic patients, whereas the latter had a lower immune response to therapy. CONCLUSIONS: The results support the idea that "maintenance" immunotherapy may not develop resistance over time in terms of biological response and thus may have a role as chronic therapy in combination with other drugs such as target therapy. We suppose that the immune system of patients with metastases is in a state of relative impairment, resulting in less sensitivity to immunostimulating agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/imunologia , Fatores Imunológicos/administração & dosagem , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Renais/imunologia , Linfócitos/efeitos dos fármacos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/terapia , Esquema de Medicação , Feminino , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Nefrectomia , Resultado do Tratamento
16.
Acta Biomed ; 83(2): 88-94, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23393915

RESUMO

BACKGROUND AND AIM OF THE WORK: Sunitinib 50 mg/day given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard treatment for metastatic renal cell carcinoma, but several patients are forced to reduce the doses and/or had to discontinue therapy permanently due to toxicity. Recent data showed that increased exposure to sunitinib is associated with improved clinical outcome underlining the key role of dose-intensity in the efficacy/toxicity balance. We investigated the tolerability and efficacy of a modified schedule. PATIENTS AND METHODS: This is a retrospective analysis which assessed consecutive non-progressive metastatic renal cell carcinoma patients admitted to our hospital who had at least a grade 2 toxicity during sunitinib therapy, and then switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet/day for 5 consecutive days a week (days 6 and 7 off therapy) for 5 weeks and 1 tablet/day on days 1, 3 and 5 in the sixth week (days 2, 4, 6 and 7 off therapy) until disease progression. Primary end points were toxicity changes assessment and schedule feasibility. RESULTS: Complete data from eight nephrectomized patients were collected: 6 males; median age 61; 3 pretreated patient. Median time from start therapy to switch was 7.4 months. After switch, treatment delays and dose reductions decreased from 50% to 25% and from 37% to 12% of patients respectively. Toxicity was reduced. CONCLUSIONS: Even though no conclusions can be drawn about the actual effectiveness and toxicity of our schedule compared to the standard dosing schedule, it seems to be well tolerated and able to maintain a high adherence to therapy, resulting in maintenance of antitumour activity. This new modified schedule requires and deserves further studies.(www.actabiomedica.it).


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Pirróis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/secundário , Progressão da Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sunitinibe , Resultado do Tratamento
17.
Oncol Rev ; 6(2): e18, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-25992216

RESUMO

Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

19.
J Immunother ; 33(7): 735-41, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20664353

RESUMO

The aim of this study was to look for the maximum tolerated dose (MTD) of gemcitabine and 5-fluorouracil in a new regimen also containing the antiangiogenic bevacizumab and immunotherapy (IT) for the treatment of metastatic renal cell cancer. The primary objective of this multicenter dose-finding study was to establish the MTD of chemotherapy (CT) in combination with fixed doses of IT and bevacizumab. The secondary objective was to assess the combination's activity. Five escalated dose levels of CT with intravenous gemcitabine and 5-fluorouracil (days 1 and 8 every 28 d), were associated together with intravenous bevacizumab (10 mg/kg on days 1 and 15 every 28 d), subcutaneous interleukin-2 (1 MIU/m² bid on days 8, 9, 15, 16, and 1 MIU/m²/d on days 10-12 and 17-19), and interferon-α-2a (3 MIU on days 10, 12, 17, 19). Of the 27 enrolled patients, 59% had been pretreated. The MTD was not reached. The highest CT dose studied was gemcitabine 1000 mg/m² and 5-fluorouracil 600 mg/m². More frequent grade 3 to 4 toxicities included neutropenia (63%), thrombocytopenia (33%), and fever (26%). The response rate was 33% according to the Response Evaluation Criteria in Solid Tumors. This is the first study that explored the feasibility and safety of combined bevacizumab, IT, and CT in metastatic renal cell cancer. The activity of this regimen is interesting and its efficacy warrants further trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renais/imunologia , Imunoterapia , Neoplasias Renais/imunologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Análise de Intenção de Tratamento , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Itália , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Dose Máxima Tolerável , Oncologia , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...