Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Eur Urol ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34602312

RESUMO

BACKGROUND: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. OBJECTIVE: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. INTERVENTION: The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. RESULTS AND LIMITATIONS: Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9-7.1) and median OS 20 mo (95% CI, 17-not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. CONCLUSIONS: We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. PATIENT SUMMARY: Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

2.
Ther Adv Urol ; 13: 17562872211054302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707691

RESUMO

Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design setting and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.

3.
Anticancer Drugs ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387593

RESUMO

Several novel androgen receptor (AR)-inhibitors have been introduced for nonmetastatic castration-resistant prostate cancer (nmCRPC) treatment, with the improvement of survival outcomes which need to be balanced against the risk of adverse events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating enzalutamide, apalutamide and darolutamide in nmCRPC patients, to assess overall survival (OS), incidence and risk of adverse drug events, adverse-events-related death and adverse-events-related treatment discontinuation. We selected three RCTs (SPARTAN, PROSPER and ARAMIS). New hormonal agents administration resulted in better OS, despite the increased risk of several any grade and grade 3-4 adverse events. In the decision-making process, careful evaluation of expected adverse events, patients' comorbidities and maintenance of quality of life are mandatory.

4.
Eur J Cancer ; 155: 56-63, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358777

RESUMO

BACKGROUND: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration. RESULTS: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%). CONCLUSIONS: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit. TRIAL REGISTRATION NUMBERS: EudraCT 2014-000175-43 - NCT02453009.

5.
Diagnostics (Basel) ; 11(6)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071518

RESUMO

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

6.
Ther Adv Med Oncol ; 13: 17588359211019642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046089

RESUMO

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

7.
Clin Genitourin Cancer ; 19(5): e286-e298, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33958297

RESUMO

INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC. PATIENTS AND METHODS: In this translational study, we employed flow cytometry to assess total, PTEN-, and AR-V7+ CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide. RESULTS: CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN- CTC, and AR-V7+ CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN- CTC count was 2 (0; 4) and median (interquartile range) AR-V7+ CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P= .021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P = .003), whereas ≥ 2 versus < 2 PTEN- CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P= .001) and OS (HR, 2.36; 95% CI, 1.12-5; P= .025). Finally, ≥ 1 versus < 1 AR-V7+ CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026). CONCLUSIONS: Despite multiple limitations, including the small sample size, our preliminary study suggests that assessment of CTC via flow cytometry may provide potentially useful prognostic and predictive information in advanced prostate cancer. Further studies are warranted. Micro-Abstract: In this study, men with metastatic castration-resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cell count and molecular characterization (total, PTEN-, and AR-V7+ circulating tumor cell count) by the use of flow cytometry. We found that flow cytometry could be used to enumerate circulating tumor cells, but also to assess molecular biomarkers on their surface.


Assuntos
Células Neoplásicas Circulantes , Neoplasias de Próstata Resistentes à Castração , Benzamidas , Biomarcadores Tumorais , Citometria de Fluxo , Humanos , Masculino , Nitrilas , PTEN Fosfo-Hidrolase/genética , Feniltioidantoína , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Isoformas de Proteínas , Receptores Androgênicos
8.
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
9.
Oncologist ; 25(10): e1509-e1515, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32735386

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.


Assuntos
COVID-19/epidemiologia , Institutos de Câncer/estatística & dados numéricos , Neoplasias Embrionárias de Células Germinativas/terapia , COVID-19/prevenção & controle , Canadá/epidemiologia , Institutos de Câncer/tendências , Europa (Continente)/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Oncologistas/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , SARS-CoV-2 , Inquéritos e Questionários , Telemedicina/tendências
11.
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
12.
Crit Rev Oncol Hematol ; 142: 141-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401421

RESUMO

Knowledge about molecular mechanisms driving development and progression of renal cell carcinoma has been elucidated by different studies. In few years we discovered a large difference between genomic landscapes of clear cell and non-clear cell carcinoma. Moreover, tumor heterogeneity and different acquisition of gene mutations during tumor progression are issues of particular interest. In this review we focalized our attention on principal genomic alterations identified among RCC subtypes. Acquired gene mutations may be an adaptive response to several external pressure including metabolic, treatment, genomic and immune-related external pressure. Thus we correlated and discussed principal genomic alterations adopted by tumor to escape from each external pressures. The aim of the present work is to summarize current knowledge about genomic alterations in RCC with special interest of treatment strategies tailored on the basis of disease mutations assessment.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Mutação , Medicina de Precisão , Animais , Carcinoma de Células Renais/genética , Genômica , Humanos , Neoplasias Renais/genética
13.
Med Oncol ; 36(9): 80, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399784

RESUMO

The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50 mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥ 50%. Median progression-free survival (PFS) and overall survival (OS) were 11 and 28 months, respectively. Median PFS and OS in the subgroup of patients with a PSA decline ≥ 50% were 14 and 35 months, respectively. Treatment was very well tolerated. We suggest that oral metronomic cyclophosphamide plus low dose of oral dexamethasone or prednisone may be a good and safe therapeutic option not only in those CRPC patients unfit for standard treatments but also in those heavily pre-treated patients.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
14.
Crit Rev Oncol Hematol ; 137: 154-164, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014511

RESUMO

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Testiculares/diagnóstico , Consenso , Seguimentos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Seminoma/diagnóstico
15.
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
16.
Anticancer Agents Med Chem ; 19(4): 567-578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706794

RESUMO

BACKGROUND: In a previous study, we synthesised a new spiroketal derivative, inspired to natural products, that has shown high antiproliferative activity, potent telomerase inhibition and proapoptotic activity on several human cell lines. OBJECTIVE: This work focused on the study of in vivo antitumor effect of this synthetic spiroketal on a murine melanoma model. In order to shed additional light on the origin of the antitumor effect, in vitro studies were performed. METHODS: Spiroketal was administered to B16F10 melanoma mice at a dose of 5 mg/Kg body weight via intraperitoneum at alternate days for 15 days. Tumor volume measures were made every 2 days starting after 12 days from cells injection. The effects of the spiroketal on tumor growth inhibition, apoptosis induction, and cell cycle modification were investigated in vitro on B16 cells. HIF1α gene expression, the inhibition of cells migration and the changes induced in cytoskeleton conformation were evaluated. RESULTS: Spiroketal displayed proapoptotic activity and high antitumor activity in B16 cells with nanomolar IC50. Moreover it has shown to inhibit cell migration, to strongly reduce the HIF1α expression and to induce strongly deterioration of cytoskeleton structure. A potent dose-dependent antitumor efficacy in syngenic B16/C57BL/6J murine model of melanoma was observed with the suppression of tumor growth by an average of 90% at a dose of 5 mg/kg. CONCLUSION: The synthesized spiroketal shows high antitumor activity in the B16 cells in vitro at nM concentration and a dose-dependent antitumor efficacy in syngenic B16/C57BL/6J mice. The results suggest that this natural product inspired spiroketal may have a potential application in melanoma therapy.


Assuntos
Antineoplásicos/farmacologia , Furanos/farmacologia , Melanoma Experimental/patologia , Compostos de Espiro/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL
17.
Cancers (Basel) ; 12(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31905816

RESUMO

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

18.
J Clin Oncol ; : JCO1800210, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30285559

RESUMO

PURPOSE: Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. PATIENTS AND METHODS: We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. RESULTS: Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. CONCLUSION: FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone.

19.
Anticancer Res ; 38(8): 4913-4918, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30061269

RESUMO

BACKGROUND/AIM: The specific characteristics of patients who are most likely to benefit from pazopanib therapy are still uncertain. We report on the results of an Italian multicenter, retrospective analysis investigating the factors associated with longer response to first-line pazopanib in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Adult patients were considered if they had received treatment with pazopanib (800 mg/day) for >12 months in the first-line setting. RESULTS: In total, 112 patients were evaluated. Median duration of pazopanib treatment was 22.6 months (IQR 17.8 months). Median PFS was 22.6 months (95%CI= 20.2-25.0). Eighty-three patients (74.1%) had a PFS ≥18 months. Median OS was 32.9 months (95%CI=30.2-35.6). At statistical analysis, only PS score (1+ vs. 0) was significantly associated with PFS (HR=1.76; 95%CI=1.02-3.05; p=0.04). CONCLUSION: Pazopanib therapy may be suitable for all patients with mRCC, and especially in those with PS 0.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Eur Urol Focus ; 4(6): 874-879, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-28753882

RESUMO

BACKGROUND: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. OBJECTIVE: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. DESIGN, SETTING, AND PARTICIPANTS: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. RESULTS AND LIMITATIONS: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p<0.001) and multivariable analysis (HR 0.40, 95% CI 0.27-0.59; p<0.001) and was significantly associated with PSA declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p<0.001). CONCLUSIONS: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. PATIENT SUMMARY: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...