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BACKGROUND: We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups. PATIENTS AND METHODS: From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS). RESULTS: After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable). CONCLUSION: Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.
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Quimioterapia Adjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Adolescente , Adulto , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Nomogramas , Orquiectomia , Fatores de Risco , Seminoma/patologia , Seminoma/cirurgiaRESUMO
BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.
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Neoplasias Ósseas/tratamento farmacológico , Remodelação Óssea , Carcinoma de Células Renais/metabolismo , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias Renais/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Biomarcadores Tumorais/sangue , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Osso e Ossos/enzimologia , Osso e Ossos/metabolismo , Carcinoma de Células Renais/mortalidade , Colágeno Tipo I/sangue , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Estudos Prospectivos , Resultado do Tratamento , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Ácido ZoledrônicoRESUMO
BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.
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Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Remodelação Óssea , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Fatores de Risco , Análise de Sobrevida , Ácido ZoledrônicoRESUMO
BACKGROUND: Cetuximab combined with radiotherapy (RT) is a treatment option for head and neck cancer. The objectives of this randomized, phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer. PATIENTS AND METHODS: Ninety-one patients with stage III-IV M0 oropharyngeal tumors were randomly assigned to the treatment with accelerated concomitant boost RT (69.9 Gy) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy. The primary end point was locoregional control (LRC) at 1 year. RESULTS: LRC at 1 year was superior among patients in the experimental arm, treated with cetuximab maintenance (59% versus 47%). However, LRC was similar between both arms after 2 years of follow-up, as a result of increased locoregional recurrences after the first year in the maintenance group. Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment. CONCLUSIONS: Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year. This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cetuximab , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: A strong rationale supports the role of antiangiogenic drugs in urothelial cancer. This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit. PATIENTS AND METHODS: This was a multicenter phase II trial with sunitinib 50 mg daily in 4/2-week schedule. Eligibility criteria were as follows: creatinine clearance 30-60 ml/min, Eastern Cooperative Oncology Group Pperformance Sstatus of one or less, and adequate hepatic and hematologic function. Twelve circulating cytokines were evaluated at baseline and sequentially using Luminex xMAP(®) (Austin, TX). Baseline and treatment-related changes in perfusion were evaluated in a patient subgroup using contrast-enhanced computed tomography. RESULTS: On intention-to-treat analysis, 38 patients showed 3 (8%) partial responses (PRs) and 19 (50%) presented with stable disease (SD), 17 (45%) of them ≥3 months. Clinical benefit (PR + SD) was 58%. Median time to progression (TTP) was 4.8 months and median overall survival 8.1 months. Toxicity was consistent with previous reports for sunitinib. Low interleukin-8 (IL-8) baseline levels were significantly associated with increased TTP. Baseline tumor contrast enhancement with >40 Hounsfield units was associated with clinical benefit. CONCLUSIONS: This study highlights the potential role of the angiogenic pathway as a therapy target in urothelial cancer. Baseline IL-8 serum levels and contrast enhancement of lesions warrant further study.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Indóis/uso terapêutico , Interleucina-8/sangue , Pirróis/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/irrigação sanguínea , Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/mortalidade , Meios de Contraste , Intervalo Livre de Doença , Feminino , Humanos , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pirróis/efeitos adversos , Sunitinibe , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Urológicas/irrigação sanguínea , Neoplasias Urológicas/diagnóstico por imagem , Neoplasias Urológicas/mortalidadeRESUMO
BACKGROUND: There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. PATIENTS AND METHODS: CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan-Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. RESULTS: The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). CONCLUSIONS: High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.
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Neoplasias de Próstata Resistentes à Castração , Androstenos , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Humanos , Linfócitos , Masculino , Neutrófilos , Nitrilas , Feniltioidantoína , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , TaxoidesRESUMO
BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.
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Códon/genética , Tumores do Estroma Gastrointestinal/genética , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas c-kit/genética , Deleção de Sequência/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Because the evidence is not yet solid enough to strongly recommend whether or not to treat hormone-refractory prostate cancer (HRPC) patients at certain stages of the disease, predictive models might help in decision making. The importance of prognostic models lies in their ability to capture clinically relevant and measurable variables for routine use by clinicians to inform patients, and improve palliation and treatment decisions. Basically this allows for the creation of homogeneous prognostic strata for randomised comparative trials of therapeutic agents. In the last few years different models to predict patient outcome in HRPC have been published in the literature. Recently, based on the phase III randomised trial of docetaxel, a multivariate prognostic model incorporating PSA kinetics has been developed to predict survival at 1, 2 and 5 years in metastatic HRPC men treated with chemotherapy. This novel model includes new independent clinical prognostic factors in addition to PSA-DT such as baseline pain, type of progression at baseline (measurable disease or bone scan compared with PSA only), presence of liver metastases and the number of metastatic disease sites. This nomogram will be a helpful tool to stratify patients for further docetaxel-based trials and could also help us to delineate the potential benefits of chemotherapy at certain points during the natural history of HRPC.
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Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/uso terapêutico , Progressão da Doença , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Humanos , Cinética , Masculino , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxoides/uso terapêuticoRESUMO
Despite the improvement provided by androgenic suppression in the treatment of prostate cancer, most of tumors develop resistance to castration. However, new therapies have demonstrated an increase in patient survival such as radium-223 (Ra-223), an alpha emitter and calcium mimetic with the capability of targeting osteoblastic metastatic lesions. According to results of the ALSYMPCA phase III trial, Ra-223 has demonstrated its activity by improving symptoms and survival of patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases, and no known visceral metastatic disease, without interfering with subsequent treatments. This review examines the key evidence to establish the best patient selection criteria to use Ra-223, how to assess the response to treatment, treatment-related toxicity, and follow-up, but also current research regarding imaging techniques and biomarkers to assess the efficacy of Ra-223. Finally, we briefly describe the clinical trials that are currently ongoing with Ra-223.
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Neoplasias Ósseas/radioterapia , Seleção de Pacientes , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/uso terapêutico , Neoplasias Ósseas/secundário , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.
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Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Humanos , MasculinoRESUMO
The original article shows two mistakes, which are listed here.
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The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the "in vitro" cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs) and polypurine reverse Hoogsteen hairpins (PPRHs), were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following results were obtained: 1) only 2'-OMe-PS-ASO reached gene silencing efficacy "in vitro"; 2) an improved survival effect was achieved combining both therapeutic vaccine and Foxp3 antisense or CTLA4 antisense oligonucleotides (50% and 20%, respectively); 3) The blood CD4+CD25+Foxp3+ (Treg) and CD4+CTLA4+ cell counts were higher in mice that developed tumor on the day of sacrifice. Our data showed that tumor cell vaccine combined with Foxp3 or CTLA4 gene silencing can increase the efficacy of therapeutic antitumor vaccination.
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OBJECTIVE: To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. MATERIALS AND METHODS: 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. RESULTS: Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). CONCLUSIONS: Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ.
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Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Idoso , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Estudos Retrospectivos , Testosterona/sangueRESUMO
PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Análise de Sobrevida , GencitabinaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aneurisma Aórtico/induzido quimicamente , Dissecção Aórtica/induzido quimicamente , Benzenossulfonatos/efeitos adversos , Piridinas/efeitos adversos , Idoso , Anti-Hipertensivos/uso terapêutico , Capecitabina , Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Hipertensão/induzido quimicamente , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sorafenibe , GencitabinaAssuntos
Porocarcinoma Écrino/diagnóstico , Doenças dos Genitais Masculinos/diagnóstico , Linfedema/diagnóstico , Escroto , Neoplasias das Glândulas Sudoríparas/diagnóstico , Idoso , Diagnóstico Diferencial , Doenças dos Genitais Masculinos/patologia , Humanos , Linfedema/patologia , Masculino , Escroto/patologiaRESUMO
CONTEXT: High school completion (HSC) is an established predictor of long-term morbidity and mortality. U.S. rates of HSC are substantially lower among students from low-income families and most racial/ethnic minority populations than students from high-income families and the non-Hispanic white population. This systematic review assesses the effectiveness of programs to increase HSC and the potential of these programs to improve lifelong health among at-risk students. EVIDENCE ACQUISITION: A search located a meta-analysis (search period 1985-2010/2011) on the effects of programs to increase HSC or General Educational Development (GED) diploma receipt; the meta-analysis was concordant with Community Guide definitions and methodologic standards. Programs were assessed separately for the general student population (152 studies) and students who were parents or pregnant (15 studies). A search for studies published between 2010 and August 2012 located ten more recent studies, which were assessed for consistency with the meta-analysis. Analyses were conducted in 2013. EVIDENCE SYNTHESIS: The review focused on the meta-analysis. Program effectiveness was measured as the increased rate of HSC (or GED receipt) by the intervention group compared with controls. All assessed program types were effective in increasing HSC in the general student population: vocational training, alternative schooling, social-emotional skills training, college-oriented programming, mentoring and counseling, supplemental academic services, school and class restructuring, multiservice packages, attendance monitoring and contingencies, community service, and case management. For students who had children or were pregnant, attendance monitoring and multiservice packages were effective. Ten studies published after the search period for the meta-analysis were consistent with its findings. CONCLUSIONS: There is strong evidence that a variety of HSC programs can improve high school or GED completion rates. Because many programs are targeted to high-risk students and communities, they are likely to advance health equity.
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Equidade em Saúde , Instituições Acadêmicas , Adolescente , Escolaridade , HumanosRESUMO
Antiemetic activity of three protracted regimens for the control of cisplatin-evoked delayed emesis was explored. 63 patients were randomly assigned to receive one of three protracted antiemetic schedules over 4 days. Group C patients received dexamethasone 8 mg twice daily on days 2 and 3, then 4 mg twice daily on days 4 and 5; in group B, alizapride 2.5 mg/kg four times daily on days 2-5 plus dexamethasone as in group C was administered; and in group A, metoclopramide 0.5 mg/kg four times daily on days 2-5 plus dexamethasone was given at the same dose-schedule as in groups C and B. Complete protection from delayed vomiting was achieved in 44% of group C, 30% of B and 70% of group A (P = 0.02). Mild side-effects were noted in all three groups. A higher complete protection for delayed emesis was obtained in metoclopramide-dexamethasone-treated patients. Neither of the regimens used in the protection of delayed emesis controlled late nausea.
Assuntos
Antieméticos/uso terapêutico , Cisplatino/efeitos adversos , Vômito/induzido quimicamente , Adulto , Idoso , Dexametasona/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metoclopramida/uso terapêutico , Pessoa de Meia-Idade , Pirrolidinas/uso terapêutico , Método Simples-Cego , Fatores de TempoRESUMO
Transitional cell carcinoma (TCC) of the urothelium is a highly chemosensitive tumour. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. At present, the combination of cisplatin, methotrexate, doxorubicin and vinblastine (M-VAC) is the most widely used for advanced TCC with an overall response rate of 40-72% in phase II, and 35-45% in phase III studies, and a median survival of approximately 12 months. These modest results and the unsuccessful attempts to increase efficacy with dose intensive M-VAC schedules have prompted the identification of new active agents in TCC, such as the taxanes and gemcitabine. The overall response rates for two-drug regimens of cisplatin-paclitaxel, carboplatin-paclitaxel and cisplatin-gemcitabine range from 63 to 72%, 14 to 65% and 42 to 66%, respectively. The overall response rates for platinum-paclitaxel-gemcitabine three-drug regimens range from 58 to 80%. The potential clinical benefit of these new three-drug combinations in the treatment of TCC needs to be tested in future phase III studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Cisplatino/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ciclofosfamida/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Vimblastina/administração & dosagem , GencitabinaRESUMO
Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. As shown in a recent phase III trial, the new gold standard should be considered gemcitabine/cisplatin, although toxicity remains important. Bladder cancer is a common tumor in our population (Spain), usually affecting elderly patients with comorbid diseases and renal impairment. Thus, most of these patients may not benefit from cisplatin-based regimens. The development of new combinations for treating such patients is, therefore, of vital importance. The identification of new active agents against transitional cell carcinoma, such as taxanes and gemcitabine, is promising. We believe that the combination of gemcitabine plus carboplatin could also be useful in this subset of patients. On this basis, we treated bladder cancer patients in two trials using gemcitabine 1,000 mg/m(2) on days 1 and 8, and carboplatin (area under the curve 5) on day 1, every 21 days. The overall response rate for evaluable patients with and without renal impairment was 60%, with a 95% confidence interval of 40% to 72%. The potential clinical benefit of this new doublet in the treatment of transitional cell carcinoma warrants testing in future phase III studies. Semin Oncol 28 (suppl 10):19-24.