Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Ann Oncol ; 27(4): 706-11, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26658889

RESUMO

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Terapia de Alvo Molecular , Prognóstico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Carcinoma de Células Renais/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Indazóis , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Espanha , Sulfonamidas/efeitos adversos
2.
Ann Oncol ; 25(11): 2173-2178, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25210015

RESUMO

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.


Assuntos
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/cirurgia
3.
Clin Transl Oncol ; 16(11): 959-65, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24719184

RESUMO

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Análise de Sobrevida , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/mortalidade , Adulto Jovem
4.
Clin Transl Oncol ; 13(12): 869-77, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22126730

RESUMO

INTRODUCTION Sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, delays disease progression, with a median overall survival (OS) of more than 2 years, improves quality of life and is becoming the first-line standard of care for metastatic renal carcinoma (mRCC). PURPOSE To assess the economic value of sunitinib as fi rst-line therapy in mRCC within the Spanish healthcare system. METHODS An adapted Markov model with a 10-year time horizon was used to analyse the cost effectiveness of sunitinib vs. sorafenib (SFN) and bevacizumab/interferon-α (BEV/IFN) as first-line mRCC therapy from the Spanish third-party payer perspective. Progression-free survival (PFS) and OS data from sunitinib, SFN and BEV/IFN pivotal trials were extrapolated to project survival and costs in 6-week cycles. Results, in progression-free life-years (PFLY), life years (LY) and quality-adjusted life-years (QALY) gained, expressed as incremental cost-effectiveness ratios (ICER) with costs and benefits discounted annually at 3%, were obtained using deterministic and probabilistic analyses. RESULTS Sunitinib was more effective and less costly than both SFN (gains of 0.52 PFLY, 0.16 LY, 0.17 QALY) and BEV/IFN (gains of 0.19 PFLY, 0.23 LY, 0.16 QALY) with average cost savings/patients of €1,124 and €23,218, respectively. Using a willingness-to-pay (WTP) threshold of €50,000/QALY, sunitinib achieved an incremental net benefit (INB) of €9,717 and €31,211 compared with SFN and BEV/IFN, respectively. At this WTP, the probability of sunitinib providing the highest INB was 75%. CONCLUSION Our analysis suggests that sunitinib is a costeffective alternative to other targeted therapies as first-line mRCC therapy in the Spanish healthcare setting.


Assuntos
Inibidores da Angiogênese/economia , Carcinoma de Células Renais/economia , Indóis/economia , Neoplasias Renais/economia , Modelos Econômicos , Pirróis/economia , Inibidores da Angiogênese/uso terapêutico , Antivirais/economia , Antivirais/uso terapêutico , Benzenossulfonatos/economia , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Humanos , Indóis/uso terapêutico , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Cadeias de Markov , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Sorafenibe , Sunitinibe
5.
Lung Cancer ; 71(2): 191-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20627363

RESUMO

UNLABELLED: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. In this study, we assessed whether the presence of polymorphisms in ERCC1, XPD, RRM1 and MDR1 genes can affect the efficacy and the tolerability of cisplatin and vinorelbine in NSCLC patients. MATERIAL AND METHODS: Eligible patients had histological confirmed stage IV or IIIB (with malignant pleural effusion) non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy; World Health Organization performance status (PS) 0-1. Patients received intravenous doses of vinorelbine 25 mg/m² on day 1 and 8 and cisplatin 75 mg/m² on day 1, every 21 days, for a maximum of eight cycles. RESULTS: 94 patients were included. Median age was 61 years; 84% were male; WHO performance status (PS) was 0 in 24%; and 88% of patients had stage IV disease. The median number of cycles was 6. Overall median survival was 10.92 months (95% CI 9.0-12.9). Overall median time to progression was 5.89 months (95% CI 5.2-6.6). Results of the multivariate analysis for time to progression showed that ECOG 0 (hazard ratio [HR] ECOG 1 vs. ECOG 0, 1.74; p=0.036), MDR13435CC (HR CT vs. CC, 2.01; p=0.017; HR TT vs. CC, 1.54; p=0.22), and decreasing age (HR of age, 0.97; p=0.016) were the most powerful prognostic factors significantly related to lower risk of progression. Whereas ECOG 0 was the only prognostic factor for survival (HR ECOG 1 vs. ECOG 0, 3.02; p=0.001). There was no significant association between any of the SNPs analysed and the occurrence of vinorelbine and cisplatin-related toxicity. CONCLUSION: In our results, the most important prognostic factors associated with lower risk of progression were MDR1 3435 CC genotype, PS 0 and younger age.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas , Genes MDR/genética , Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Progressão da Doença , Feminino , Frequência do Gene , Genótipo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Vinorelbina
6.
Clin Transl Oncol ; 11(5): 284-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19451061

RESUMO

Lung cancer is currently the most common malignancy and also the leading cause of mortality related to cancer in the world [1]. The crude incidence of lung cancer in the EU is 52.5/100,000/year, while the mortality 48.7/100,000/year. Among men the rates are 82.5 and 77.0/100,000/year, and among women 23.9 and 22.3/100,000/year, respectively. Non-small-cell lung cancer (NSCLC) accounts for 80% of all cases. In Spain, there were 16,879 deaths in men, with a mean age of 68 years, and 2634 deaths in women, with a mean age of 66 years. The incidence of lung cancer in Spain was 68.3/100,000 among men and 13.8/100,000 among women, according to the latest data published in the year 2006 by the Instituto Nacional de Estadística. About 90% of lung cancer mortality among men (and 80% among women) is attributable to smoking.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias
7.
Rev Esp Quimioter ; 19(1): 34-8, 2006 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-16688289

RESUMO

Helicobacter pylori possess various virulence factors, including cagA and vacA genes, that are associated with more aggressive symptoms such as bleed-ing ulcer and gastric cancer. Although there are different treatment regimens, there is still a failure rate of up to 20% due to antibiotic resistance, among other causes. In our country resistance to metronidazole and clarithromycin is increasing, especially in children, although they are still susceptible to amoxicillin and tetracycline. In order to determine the susceptibility pattern to these antibiotics 36 H. pylori clinical isolates were studied. MIC was determined by agar diffusion and agar dilution, and vacA and cagA genes were detected by conventional PCR. All isolates were susceptible to amoxicillin and tetracycline. Resistance to metronidazole by diffusion or dilution tests was 35.7% and 36.1%, respectively, and to clarithromycin, 21.4% and 22.3%, respectively. There was one strain that showed intermediate resistance to clarithromycin (MIC 0.38 mg/l), using agar diffusion, and that was included among the resistant strains. Three discrepancies were observed between the diffusion and dilution methods. The vacA s1 allele was detected in 17.2% of the strains, and vacA s2 in 82.8%; 51.7% of the total were cagA+. In conclusion, all strains tested in our study were susceptible to amoxicillin and tetracycline, allowing them to be considered as first-line antibiotics, while clarithromycin and metronidazole maintain a slight increase in their resistance level. The cagA+ strains were detected in expected quantities, while the s1 allele of the vacA gene was detected in lower quantities.


Assuntos
Amoxicilina/farmacologia , Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Metronidazol/farmacologia , Tetraciclina/farmacologia , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Criança , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Testes de Sensibilidade Microbiana , Especificidade da Espécie , Virulência/genética
8.
Ann Oncol ; 15(8): 1194-203, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15277258

RESUMO

BACKGROUND: Platinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel-cisplatin-treated stage IV NSCLC patients. PATIENTS AND METHODS: Using the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 -37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel-cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR. RESULTS: Overall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for 11 patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC1 118 genotype (P=0.03). No other significant differences were observed. CONCLUSIONS: Patients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Adutos de DNA , Reparo do DNA , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
9.
Eur Urol ; 42(6): 553-62; discussion 562-3, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12477650

RESUMO

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.


Assuntos
Germinoma/diagnóstico , Germinoma/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade
10.
Rev Esp Quimioter ; 14(2): 184-90, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11704773

RESUMO

The in vitro antibiotic activity of CA(1-8)M(1-18), a synthetic cecropin A-melittin hybrid peptide, was determined by broth microdilution on 20 clinical Acinetobacter baumannii isolates with different resistance profiles. The MIC(50), MIC(90) and ranges were 4 mg/l, 4 mg/l and 2-8 mg/l, respectively, and were independent of resistance pattern. Different assay parameters such as microplate plastic (polystyrene or polypropylene), addition of supplements (5-10% fetal calf serum or 5% horse blood), inoculum size (10(5), 10(6), 10(7) and 10(8) CFU/ml) or incubation period (24 or 48 h) were studied. MIC was independent of the first two parameters, although the MIC values increased both with inoculum size or incubation period. Killing curves were obtained both for a standard strain and a multiresistant isolate over a 45.7-2.8 mg/l (16-1 mM) peptide range, using an initial inoculum of 10(5)-10(6) CFU/ml and 10(9)-10(10) CFU/ml. A concentration of 45.7 mg/l was required for complete killing. Accordingly, CA(1-8)M(1-18) showed good in vitro activity against the A. baumannii strains tested irrespective of the resistance to classical antibiotics, and could be a future candidate for multiresistant A. baumannii infections, although further cytotoxicity and pharmacological studies will be needed.


Assuntos
Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Meliteno/farmacologia , Fragmentos de Peptídeos/farmacologia , Acinetobacter/isolamento & purificação , Infecções por Acinetobacter/microbiologia , Peptídeos Catiônicos Antimicrobianos/química , Resistência a Medicamentos , Resistência a Múltiplos Medicamentos , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Testes de Sensibilidade Microbiana/métodos
11.
J Natl Cancer Inst ; 93(1): 31-8, 2001 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-11136839

RESUMO

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia. METHODS: A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided. RESULTS: Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm. CONCLUSIONS: Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Febre/etiologia , Fator Estimulador de Colônias de Granulócitos/economia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Análise Custo-Benefício , Esquema de Medicação , Feminino , Febre/induzido quimicamente , Febre/microbiologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Modelos de Riscos Proporcionais , Estudos Prospectivos , Espanha , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
J Clin Oncol ; 18(18): 3247-55, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10986057

RESUMO

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.


Assuntos
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 , Gencitabina
14.
Rev Esp Quimioter ; 13(4): 408-11, 2000 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-11498709

RESUMO

The aim of this study was to determine the in vitro activity of ascorbic acid (vitamin C) against 43 Helicobacter pylori clinical isolates obtained from gastric biopsy taken by endoscopy. The MIC was determined by an agar dilution method. The ascorbic acid was included as two-fold dilutions in the agar to obtain a final concentration from 4000 mg/l to 62 mg/l. Brain-heart infusion agar supplemented with yeast extract and 10% fetal calf serum, 10(6) CFU/spot inoculum and microaerobic incubation for 2 to 5 days were used. MIC(50) 500 mg/l, MIC(90) 1000 mg/l and the range from 62 to 2000 mg/l. No differences in susceptible or resistant isolates were observed. Ascorbic acid showed good in vitro activity against the H. pylori clinical isolates tested in this study, which could explain some of the beneficial properties of vitamin C.


Assuntos
Ácido Ascórbico/farmacologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana
16.
Arch Esp Urol ; 52(4): 399-401, 1999 May.
Artigo em Espanhol | MEDLINE | ID: mdl-10380334

RESUMO

OBJECTIVE: To report a case of primary germ cell testicular tumor that spontaneously remitted after metastasizing to the retroperitoneum, leaving histologically characteristic lesions of a fused tumor. The characteristic testicular ultrasound findings that permitted the diagnosis are described. METHODS/RESULTS: A 21-year-old male consulted for a retroperitoneal mass. The testes were normal on palpation. The testicular ultrasound showed a hyperechoic area with an acoustic shadow suspected as being a tumoral cicatrix. The histological analysis after orchidectomy revealed a mixed non-seminomatous germ cell tumor. CONCLUSIONS: Testicular ultrasound evaluation should be performed on all patients with retrosperitoneal germ cell tumor and normal testes on palpation. In the case described, there was good correlation between the ultrasound and the histological findings.


Assuntos
Germinoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Adulto , Germinoma/cirurgia , Humanos , Masculino , Orquiectomia , Neoplasias Testiculares/cirurgia
17.
Rev Esp Quimioter ; 12(1): 64-8, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10209056

RESUMO

Ranitidine bismuth citrate is a novel salt that seems to be useful in eradication of Helicobacter pylori from gastric mucosa when it is combined with antibiotics. The in vitro bacteriostatic (by MIC determination) and bactericidal (by killing curve) activity of ranitidine bismuth citrate was determined in this study. A total of 52 strains were cultured from gastric antral biopsy specimens taken at routine endoscopy and identified using standard methodology. MIC was determined by agar dilution using Mueller-Hinton agar supplemented with 7% horse blood. Killing curves were studied in 11 isolates. Ranitidine bismuth citrate at final concentrations of 1 mg/l and 8 mg/l were used. A starting inoculum of 10(4) to 10(6) CFU/ml was prepared in BHI with 10% fetal calf serum from a 48 h H. pylori broth culture. Viable colony counting was performed at 0, 2, 4, 6, 8 and 24 h. A control without the study drug was included in each experiment and treated identically. A reduction of 100 to 1,000 CFU/ml was considered bactericidal. The MIC50, MIC90 and range for ranitidine bismuth citrate was 1, 2 and 0.25-4 mg/l, respectively. At 1 mg/l it showed a bactericidal effect after 2 h in one strain, after 8 h in two and after 24 h in four strains, and four strains were not killed. At 8 mg/l it killed three strains in 2 h, one in 4 h, two in 6 h, one in 8 h and four strains in 24 h. Ranitidine bismuth citrate was active in vitro against the H. pylori clinical isolates tested (by MIC and killing curves).


Assuntos
Antiulcerosos/farmacologia , Bismuto/farmacologia , Helicobacter pylori/efeitos dos fármacos , Ranitidina/análogos & derivados , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Ranitidina/farmacologia
19.
Rev Esp Quimioter ; 12(4): 340-5, 1999 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-10855013

RESUMO

The aim of this study was to determine the relationship between the antibiotic susceptibility and different virulence factors among Helicobacter pylori clinical isolates. One hundred and forty-five strains were isolated from biopsy cultures obtained from adult patients. Antimicrobial susceptibility to amoxicillin, clarithromycin, metronidazole and tetracycline were tested using an agar dilution method. cagA and iceA genes and s1 and s2 alleles of vacA were studied by polymerase chain reaction. A group of patients had been previously treated for H. pylori infection. We found a resistance rate of 28.7% and 16.5% to metronidazole and clarithromycin, respectively. We did not find any resistance to amoxicillin or tetracycline. The cagA gene and s1 allele were detected in 86.3% and 65.2% of the strains. One hundred and two (71.3%) strains were iceA+. cagA+ strains showed lower percentages of resistance to antibiotics, as did vacA s1 and iceA+ strains. The role of lower rates of resistance to clarithromycin and metronidazole in more virulent H. pylori strains may have favorable effects in their eradication in patients infected with these strains.


Assuntos
Antígenos de Bactérias , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Adulto , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Virulência
20.
Rev Esp Quimioter ; 12(4): 340-345, 1999.
Artigo em Espanhol | MEDLINE | ID: mdl-10878526

RESUMO

The aim of this study was to determine the relationship between the antibiotic susceptibility and different virulence factors among Helicobacter pylori clinical isolates. One hundred and forty-five strains were isolated from biopsy cultures obtained from adult patients. Antimicrobial susceptibility to amoxicillin, clarithromycin, metronidazole and tetracycline were tested using an agar dilution method. cagA and iceA genes and s1 and s2 alleles of vacA were studied by polymerase chain reaction. A group of patients had been previously treated for H. pylori infection. We found a resistance rate of 28.7% and 16.5% to metronidazole and clarithromycin, respectively. We did not find any resistance to amoxicillin or tetracycline. The cagA gene and s1 allele were detected in 86.3% and 65.2% of the strains. One hundred and two (71.3%) strains were iceA+. cagA+ strains showed lower percentages of resistance to antibiotics, as did vacA s1 and iceA+ strains. The role of lower rates of resistance to clarithromycin and metronidazole in more virulent H. pylori strains may have favorable effects in their eradication in patients infected with these strains.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA