RESUMO
Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are not used in clinical practice. Probabilistic graphical models and classificatory algorithms were used to classify melanoma tumor samples from a TCGA cohort. A cohort of patients with advanced melanoma treated with PD-1 inhibitors was also analyzed. We established that gene expression data can be grouped in two different layers of information: immune and molecular. In the TCGA, the molecular classification provided information on processes such as epidermis development and keratinization, melanogenesis, and extracellular space and membrane. The immune layer classification was able to distinguish between responders and non-responders to immunotherapy in an independent series of patients with advanced melanoma treated with PD-1 inhibitors. We established that the immune information is independent than molecular features of the tumors in melanoma TCGA cohort, and an immune classification of these tumors was established. This immune classification was capable to determine what patients are going to respond to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors Therefore, this immune signature could be useful to the clinicians to identify those patients who will respond to immunotherapy.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Transcriptoma , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , ImunoterapiaRESUMO
BACKGROUND: Spain has been severely affected by the COVID-19 epidemic, with 195,944 persons infected and 20,453 deaths at the time of writing. Older people with respiratory or cardiac conditions are most at risk. OBJECTIVE: The aim was to compare respiratory symptoms in nursing home residents and patients with uncontrolled asthma, who are considered vulnerable to COVID-19. METHODS: We studied 134 nursing home residents and 139 patients with uncontrolled asthma, groups vulnerable to COVID-19. Demographic characteristics, clinical manifestations, outcomes, key laboratory results, and radiological images were collected from medical records. COVID-19 infection was detected by polymerase chain reaction (PCR). RESULTS: Thirteen (9.3%) patients with uncontrolled asthma, all receiving inhaled corticosteroids were infected by COVID-19. Eighty (60%) nursing home residents were infected; only 28, all of whom had received inhaled corticosteroids, had a good prognosis. CONCLUSIONS: Early treatment with inhaled corticosteroids may be helpful in COVID-19 infection. Persons with an allergy might have some protective mechanisms against coronavirus.
Assuntos
Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , COVID-19/prevenção & controle , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/virologia , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19 , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Prognóstico , EspanhaRESUMO
BACKGROUND: Recurrent, metastatic, and locally advanced gastrointestinal stromal tumors (GISTs) can be treated successfully with imatinib mesylate. Surgery for residual disease has been suggested for nonrefractory metastatic GISTs to reduce the probability of resistant recurrent clones, although no randomized Phase III trial has been performed to answer the question about its benefit. We carried out an analysis of the outcome of patients with recurrent unresectable locally advanced or metastatic imatinib-sensitive priamary GIST in 14 institutions in Spain. We compared two cohorts: treated or not treated with surgery after partial response or stabilization by imatinib. PATIENTS AND METHODS: Data were obtained from the online GIST registry of the Spanish Group for Research in Sarcomas. Selected patients were then divided into two groups: group A, treated initially only with imatinib, and group B, treated additionally with metastasectomy. Baseline characteristics between groups were compared, and univariate and multivariate analysis for progression-free survival and overall survival (OS) were performed. RESULTS: Analysis was undertaken in 171 patients considered nonrefractory to imatinib. The median follow-up time was 56.6 months. Focusing on OS, the Eastern Cooperative Oncology Group performance status different than 0, extent of disease limited to one metastatic organ, and comparison between groups A or B achieved statistical difference in the multivariate analysis. Median survival was 59.9 months in group A and 87.6 months in group B. CONCLUSIONS: Based in its benefit in OS, our study supports surgery of metastatic disease in GIST patients who respond to imatinib therapy.
Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/cirurgia , Mesilato de Imatinib/uso terapêutico , Metastasectomia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Terapia Combinada , Feminino , Seguimentos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment.
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Topotecan, a semi-synthetic camptothecin analogue with topoisomerase I interaction, has shown to be an active agent in the treatment of advanced refractory lung cancer. This paper describes the authors' experience with this drug when used as a single agent in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to platinum- and taxane-containing chemotherapy regimens. Thirty-five patients with NSCLC refractory to previous chemotherapy and KI ≥ 60% were included in the study. Their characteristics are as follows: median age of 52 years (range 43-69) and Karnofsky PS of 70 (60-80); 27 were male and 8 were female. Twenty-one (60%) patients had adenocarcinoma; eleven (31.4%), squamous cell, and three (8.5%), undifferentiated carcinoma. There was a median of two disease sites and two prior chemotherapy regimens. Topotecan was administered at a dose of 1.25 mg/m(2) I.V. daily for 5 days, repeated every 21 days until disease progression, maximal response, or intolerable toxicity. After 73 cycles, patients received a median of 2 treatment cycles (1-9). All patients except one were considered evaluable for toxicity; eight episodes (24%) of nausea/vomiting and two episodes (6%) of grade 1-2 asthenia, respectively, were reported. Four (12%) patients developed grade 1-2 anemia and two (6%) subjects suffered grade 3 anemia. Seven (21%) patients had grade 1-2 neutropenia and one (3%) presented grade 5 neutropenia. In 33 patients evaluable for activity of the 35 subjects included in the study; one (2.8%) presented a partial response; nine (25.7%) had stable disease, and 23 (65.7%) exhibited disease progression. Median time to progression and overall survival were 54 (12-210) and 70 (12-324) days, respectively. Intravenous topotecan at that dose and administration schedule displays scant activity in terms of response rate in individuals with advanced NSCLC previously treated with platinum and taxanes. The role and usefulness of chemotherapy in this setting warrants further investigation and confirmation through comparative studies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores da Topoisomerase I/uso terapêutico , Topotecan/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Estudos Prospectivos , Sobrevida , Taxoides/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos , Topotecan/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Pegylated liposomal doxorubicin (PLD) is currently the reference treatment for platinum-resistant ovarian cancer. The combination of PLD and gemcitabine and the administration of gemcitabine at a fixed dose rate infusion (FDRI) seem to have additive activity in this disease setting. We have launched a phase Ib study with the combination of FDRI gemcitabine followed by PLD in recurrent ovarian cancer with a platinum-free interval of less than 1 year, with parallel pharmacokinetic and pharmacogenetic studies. METHODS: The starting dose of gemcitabine was 1500 mg/m², 10 mg/m² per minute, every 2 weeks (± 250 mg gemcitabine titration depending on toxicity), followed by PLD 35 mg/m² every 4 weeks. Gemcitabine pharmacokinetics and equilibrative nucleoside transporter 1, deoxycytidine kinase, and ribonucleotide reductase M1 gene expression levels were studied. RESULTS: Thirty-five patients were treated at 3 different dose levels (DL). Dose level 1 was not tolerated. Nonfrail patients continued to be treated at DL-1 (G 1250 mg/m² on day 1 and PLD 35 mg/m² on days 1 and 15). Of 10 evaluable nonfrail patients, 4 displayed dose-limiting toxicity. Frail patients were treated at DL-2 (G 1250 mg/m on day 1 and PLD 35 mg/m² on days 1 and 15). Of the 12 evaluable frail patients, 3 developed dose-limiting toxicity. Neutropenia, palmar-plantar erythrodysesthesia and stomatitis were the most common toxicities. The response rate was 42.8% (95% confidence interval [CI], 34.5%-51.1%), with 17.1% (6/35) complete responses and 25.7% (9/35) partial responses. The median progression-free survival was 7.7 months (95% CI, 2.2-13.1). The median overall survival was 13.9 months (95% CI, 9.4-18.4). The administration of PLD after gemcitabine did not influence gemcitabine pharmacokinetics or its metabolites. The addition of PLD to gemcitabine caused a larger and longer induction of the ribonucleotide reductase M1 gene. Patients with higher baseline levels of deoxycytidine kinase had longer progression-free survival. CONCLUSION: The recommended dose for a phase II study of patients with recurrent ovarian cancer having poor prognosis is PLD, 35 mg/m² on day 1, and gemcitabine, 1000 mg/m² on days 1 and 15 delivered at an FDRI of 10 mg/m per minute in 28-day cycles.
Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polietilenoglicóis/administração & dosagem , Taxa de Sobrevida , Distribuição Tecidual , Resultado do Tratamento , GencitabinaRESUMO
Patient was a 52-year-old woman with medical history of lung adenocarcinoma operated in 2009 (stage I, T2 N0 M0), showing increasing levels of tumor markers and a doubtful retrocrural adenopathy by means of CT scan with intravenous contrast. An F-FDG PET/CT was performed, which showed 2 hypermetabolic foci in both annexes. The anatomopathological study detected bilateral ovarian adenocarcinoma compatible with metastases of pulmonary origin.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenocarcinoma de Pulmão/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Compostos RadiofarmacêuticosRESUMO
To evaluate possible improvement in objective response of adding vinorelbine (V) to the combination of cisplatin/gemcitabine (CG) in induction chemotherapy for stage III NSCLC, patients (n=154) aged < or =75 years, Karnofsky index > or =70%, were stratified by stage (IIIA versus IIIB) and randomly assigned to receive: C (50mg/m(2) i.v.) plus G (1250mg/m(2) i.v.) or CG plus V (25mg/m(2) i.v.). All drugs were administered on days 1 and 8 of an every 3-week cycle. At conclusion, local treatment (LT) with surgery and/or radiotherapy was scheduled. The results indicated that, following a median of 3 cycles, the overall efficacy was 65% in the CG and 61% in the CGV group. Most patients in both groups received radiotherapy as part of their LT. Pathological complete response was confirmed by surgery in 18% in the CG and 25% in the CGV group. Median progression-free survival was 368 days in the CG and 322 days in the CGV group. There were no statistically significant differences in toxicities between groups. We conclude that the CG and CGV combinations had similar efficacy and moderate toxicity, without accruing to the triplet combination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
BACKGROUND: Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS). METHODS: Ninety-two advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF1R system, we have used an antibody (anti-pY1316) that specifically recognizes the active phosphorylated form of the IGF1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9, 11, 13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirectional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p < 0.10 and criterion to keep the variable in the model of p < 0.05. PFS was computed as the date of imatinib initiation to progression or death. Overall survival was defined as the time from imatinib initiation to death. RESULTS: Phospho-IGF1R was expressed only in 9 % (2/22) of cases without KIT mutation. MMP3 expression was detected in 2/5 patients (40 %) with PDGFRA mutation, 1/16 patients (6 %) with WT genotype and 7/71 patients (10 %) of KIT mutant patients. At univariate analysis KIT exon 11/13 mutation had better PFS than patients with exon 9 mutation, PDGFRA mutation or WT genotype (p = 0.021; HR: 0.46; 95 %CI (0.28-0.76). Less than 24 months disease free-interval (HR 24.2, 95 % CI 10.5-55.8), poor performance status (PS) (HR 6.3, 95 % CI 2.5-15.9), extension of disease; >1 organ (HR 1.89; 95 % CI 1.03-3.4) and genotype analysis (HR 0.57, 95 % CI 0.37-0.97) but not immunophenotype analysis (HR 1.53; 95 % CI 0.76-3.06) were the strongest prognostic factors for PFS in the multivariate analysis. CONCLUSIONS: Our results do not support p-IGF-1R and MMP3 evaluation in non-selected GIST patients but evaluation of this immunophenotype in WT and mutant PDGFR mutation in larger group of GIST patients, deserve merits.
RESUMO
BACKGROUND: Spain has been severely affected by the COVID-19 epidemic, with 195,944 persons infected and 20,453 deaths at the time of writing. Older people with respiratory or cardiac conditions are most at risk. OBJECTIVE: The aim was to compare respiratory symptoms in nursing home residents and patients with uncontrolled asthma, who are considered vulnerable to COVID-19.METHODS: We studied 134 nursing home residents and 139 patients with uncontrolled asthma, groups vulnerable to COVID-19. Demographic characteristics, clinical manifestations, out-comes, key laboratory results, and radiological images were collected from medical records. COVID-19 infection was detected by polymerase chain reaction (PCR).RESULTS: Thirteen (9.3%) patients with uncontrolled asthma, all receiving inhaled corticoste-roids were infected by COVID-19. Eighty (60%) nursing home residents were infected; only 28, all of whom had received inhaled corticosteroids, had a good prognosis CONCLUSIONS: Early treatment with inhaled corticosteroids may be helpful in COVID-19 infection. Persons with an allergy might have some protective mechanisms against coronavirus
No disponible
Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Internato não Médico/estatística & dados numéricos , Asma/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pandemias , Corticosteroides/administração & dosagem , Administração por Inalação , Estudos Transversais , Fatores de RiscoRESUMO
La llegada de la pandemia COVID-19 puso en evidencia el riesgo de una posible falta de atención de los ancianos de las residencias de mayores. Aportamos la experiencia de un equipo multidisciplinar con profesionales voluntarios de diferentes especialidades que realizó una labor de apoyo a los profesionales sanitarios de las residencias. Este equipo se implementó desde las gerencias de atención primaria y de atención especializada. La sistemática de trabajo se inspiraba en el de hospitalización a domicilio e incluía la atención directa de los pacientes más complejos y el asesoramiento en las medidas de prevención, aislamiento e higiene dentro de la residencia. De este modo fue posible que los ancianos de las residencias con sospecha o diagnóstico de COVID-19 recibieran una atención adecuada por parte de un equipo interdisciplinar, que se descargara parte de la presión de los profesionales de las residencias y que los familiares percibieran que no existía abandono terapéutico. El compromiso desde diversos niveles asistenciales en una labor coordinada ha conseguido evitar que una población vulnerable pudiera quedar desatendido durante la pandemia
With the arrival of the COVID-19 pandemic, the risk of a possible lack of care for the elderly in nursing homes became evident. We summarize the experience of a multidisciplinary team with volunteer professionals from different specialties who carried out support for healthcare professionals in nursing homes. This team was implemented from both Primary and Specialty Care managements. Its work paradigm was proposed by our home hospitalization team, which included direct care of the most complex patients and general counselling on isolation, hygiene and preventive measures within the nursing homes. Thanks to this support, the elderly population placed there, with suspected or diagnosed COVID-19, received adequate care from an interdisciplinary team, which led part of the pressure to be released from their professional workers, and many family members were aware that there was no neglect of the elderly. Commitment from various levels of care in a coordinated effort has prevented a vulnerable population from being left unattended during the pandemic
Assuntos
Humanos , Idoso , Instituição de Longa Permanência para Idosos/organização & administração , Direitos dos Idosos/legislação & jurisprudência , Pandemias/ética , Infecções por Coronavirus/epidemiologia , Recusa em Tratar/ética , Prioridades em Saúde/ética , Capacidade de Resposta ante Emergências/éticaRESUMO
Detection of melanoma cells in the peripheral blood of melanoma patients by reverse transcription polymerase chain reaction techniques has demonstrated varying detection rates. This study examined the sensitivity of the technique by employing a modification of the currently used protocols to detect mRNA markers. RT-PCR of tyrosinase and MART-1 was performed after poly A+-RNA isolation from unmanipulated whole blood lysed in the presence of nuclease inhibitors. We found a preclinical sensitivity of 1 GR-M melanoma cell spiked in 1 ml of blood. The clinical sensitivity was tested by studying 22 melanoma patients with advanced disease. The rate of positivity in all patients was 63.6% for tyrosinase, 50% for MRT-1 and 77.3% for at least one molecular marker. This figure increased to 89.5% when considering only those patients with evident macroscopic disease. We can conclude that the technical modifications introduced in this protocol significantly increased the clinical sensitivity compared with other published methods.
Assuntos
Melanoma/sangue , Melanoma/patologia , Células Neoplásicas Circulantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias , Feminino , Humanos , Antígeno MART-1 , Masculino , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/genética , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , RNA Mensageiro/sangue , Sensibilidade e EspecificidadeRESUMO
Because no consensus exists regarding recommendable dose levels for irinotecan, an intrapatient dose escalation phase I-II study was initiated in previously treated patients with colorectal cancer. Survival was a secondary endpoint. Thirty-five consecutive patients with progressive disease after 5-fluorouracil-based chemotherapy were enrolled to receive irinotecan starting from 250 mg/m2/3 weeks and rising to currently used therapeutic doses. In total, 162 cycles were administered. The median tolerable dose was 250 mg/m2. Twelve patients (34%) were unable to tolerate doses greater than 250 mg/m2, 10 patients (28%) presented toxicity at 250 mg/m2 and 2 patients tolerated only 200 mg/m2. Three patients (9%) had partial response. The major adverse reactions were grade III-IV diarrhea, grade II-III nausea/vomiting, grade II-III neutropenia, and grade II-III anaemia in 28%, 48%, 11%, and 17% of the patients, respectively. Median survival time and time to progression were 8 and 3 months, respectively. The current irinotecan dose of 350 mg/m2/3 weeks appears unacceptably toxic and, hence, a lower dose needs to be considered. The response rates obtained are similar to the results observed in phase III studies, and its activity appears not to be adversely affected with this treatment scheme.
Assuntos
Antineoplásicos/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Camptotecina/uso terapêutico , Quimioterapia Adjuvante , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Cuidados Paliativos , Análise de Sobrevida , Inibidores da Topoisomerase I , Falha de TratamentoRESUMO
No disponible
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Humanos , Feminino , Idoso de 80 Anos ou mais , Dor no Peito/complicações , Dor no Peito/etiologia , Dispneia/complicações , Nódulos Pulmonares Múltiplos/complicações , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Cuidados Paliativos/métodos , Redução de Peso , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Gasometria/métodos , Radiografia Torácica/métodosRESUMO
PURPOSE: To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. PATIENTS AND METHODS: Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. RESULTS: From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. CONCLUSION: The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Terapia de Salvação , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Espanha , Resultado do Tratamento , Adulto Jovem , GencitabinaAssuntos
Antineoplásicos Alquilantes/efeitos adversos , Encefalopatias/induzido quimicamente , Encefalopatias/tratamento farmacológico , Ifosfamida/efeitos adversos , Neoplasias/tratamento farmacológico , Tiamina/administração & dosagem , Adulto , Humanos , Infusões Intravenosas , Resultado do TratamentoRESUMO
INTRODUCTION: For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC. MATERIALS AND METHODS: This study was designed as a retrospective chart review of RCC patients who were treated with CKs and/or TKIs in our department between July 1996 and June 2008. Efficacy and toxicity were assessed using World Health Organization (WHO) criteria. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall (OS) survival. RESULTS: Ninety-four patients were classified into three groups depending on the modality of treatment administered: 46 were treated with CKs alone and/or chemotherapy (27 with immunotherapy, one with chemotherapy and 18 with both), 28 with TKIs alone (25 with sunitinib and 13 with sorafenib) and 20 with TKIs in second-line treatment following failure with CKs (17 with sunitinib, eight with sorafenib, four with bevacizumab and one with lapatinib). The median age was 60 years in the CK group and 65 and 62, respectively, in TKI in first and second-line treatment groups. Eighty-five percent of patients treated with CKs and 75% in the TKI group in first-line treatment and 80% in second-line treatment were men. Overall, 89% of patients had favourable risk, and 11% had intermediate risk. All patients were considered evaluable for toxicity. The main grade 3-4 (%) toxicity was asthenia for both groups, (ten in TKIs and 15 in CKs). Other grade 1-2 toxicities were mucositis (39), bleeding (8), hypertension (19), skin toxicity (33) and hypothyroidism (12.5) associated with TKIs; and anaemia (33), cough (29), asthenia (39) and emesis (14) associated with CKs. The objective response rate among 80 patients evaluable for activity was 10.6% with CKs and 46.5% and 35%, respectively, with TKIs in first- and second-line treatments. Disease stabilisation with CKs was recorded at 59% of patients and with TKIs 25% and 50% in first- and second-line treatment groups, respectively. The median progression-free survival (PFS) with CKs was 122 days [95% confidence interval (CI) 82-162] and with TKIs 201 days (65-337) in the first and 346 days (256-436) in second-line treatment groups. The median overall survival (OS) was 229 days (142-316) and 2,074 days (1,152-2,996) for patients treated with CKs and TKIs. CONCLUSIONS: Our results are in line with the activity and survival rates previously reported in the literature regarding the use of TKIs for patients with advanced RCC in first- and second-line treatment, which has demonstrated an acceptable toxicity level.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Benzenossulfonatos/administração & dosagem , Benzenossulfonatos/efeitos adversos , Benzenossulfonatos/uso terapêutico , Bevacizumab , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/uso terapêutico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Interleucina-2/uso terapêutico , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Lapatinib , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Estudos RetrospectivosRESUMO
PURPOSE: To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m(2) per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m(2) delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). RESULTS: Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). CONCLUSION: Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.
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Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Ifosfamida/administração & dosagem , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naïve patients (n=39)
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pneumopatias/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Diarreia/induzido quimicamente , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Prospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.