RESUMEN
Resumen Introducción: el mesotelioma epitelioide es un tumor que se desarrolla en las capas embrionarias mesoteliales; es de etiología desconocida, pero se relaciona con la exposición al asbesto, con una presentación clínica inespecífica y con un pronóstico de sobrevida corto después del diagnóstico. Presentación del caso: hombre de profesión mecánico automotor, con tos sin expectoración, disnea, hipertermia y emaciación posterior a la extracción quirúrgica de lipomas que afectaban el tórax, quien posteriormente fue diagnosticado con mesotelioma epitelioide maligno con ubicación en la pleura del hemitórax derecho y fue tratado con toracotomía, quimioterapia con los medicamentos pemetrexed y cisplatino y sesiones de radioterapia, que mostraron un aumento en la sobrevida 3 tres años. Conclusión: este caso permitió identificar que el uso de la pleurodesis química con quimioterapia como tratamiento podría ser responsable del aumento de la esperanza de vida y la calidad de esta en los pacientes que padecen este tipo de tumor.
Abstract Introduction: Epithelioid mesothelioma is a tumor that develops in the mesothelial embryonic layers; it is of an unknown etiology, but it is related to asbestos exposure with a nonspecific clinical presentation and a short survival prognosis after diagnosis. Case presentation: An automotive mechanic patient presents with cough without expectoration, dyspnea, hyperthermia, and emaciation following surgical removal of lipomas. This affected the chest and the patient was subsequently diagnosed with malignant epithelioid mesothelioma located in the pleura of the right hemithorax. The patient was treated with thoracotomy, chemotherapy with the drugs pemetrexed and cisplatin, and radiation therapy sessions which resulted in an increased survival rate at 4 years. Conclusion: This case report identifies the use of chemical pleurodesis in combination with chemotherapy as an effective treatment for increasing the life expectancy and quality of life in patients suffering from this type of tumor.
Resumo Introdução: o mesotelioma epitelióide é um tumor que se desenvolve nas camadas embrionárias mesote-liais; é de causa desconhecida, mas está relacionado com a exposição ao amianto e possui uma manifestação clínica inespecífica e com prognóstico de sobrevivência curto após o diagnóstico. Apresentação do caso: o paciente é um mecânico automotivo, que apresentou tosse seca, dispneia, hipertermia e emagrecimento posterior a extração cirúrgica de lipomas que afetavam o tórax sendo posteriormente diagnosticado com mesotelioma epitelióide maligno localizado na pleura do hemitórax direito e foi tratado com toracotomia, quimioterapia com os medicamentos pemetrexed e cisplatino além de sessões de radioterapia, mostrando um aumento de expectativa de vida para 4 anos. Conclusão: este estudo de caso permite identificar que o uso da pleurodese química com quimioterapia como tratamento poderia ser a responsável pelo aumento da expectativa e qualidade de vida em pacientes acometidos por este tipo de tumor.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Asbestosis , Mesodermo , Mesotelioma , Cisplatino , Colombia , PemetrexedRESUMEN
PURPOSE: KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. METHODS: Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. RESULTS: Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03-2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27-2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12-4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. CONCLUSION: Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Platino (Metal)/uso terapéutico , Supervivencia sin Progresión , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine. PATIENTS AND METHODS: A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m2 on day 1 and 100 mg/m2 on day 8 plus cisplatin 80 mg/m2 on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR). RESULTS: The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018). CONCLUSIONS: In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients. CLINICALTRIALS. GOV IDENTIFIER: NCT00614965.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Recuperativa , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed/administración & dosificación , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Thymidylate synthase (TYMS) expression in lung cancer tissue affects the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is primarily assessed using immunohistochemistry (IHC), but this method is not suitable for accurate quantitative analysis. It is not known whether the analysis of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a useful method for assessment of TYMS expression. PATIENTS AND METHODS: The participants were patients with chemo-naïve advanced NSCLC treated with PMT plus carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was evaluated in 40 patients by gene copy number and protein expression using FISH and IHC. Therapeutic efficacy was evaluated by investigating the response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: TYMS gene amplification was detected in 8 patients (32 %) among 25 patients who could be evaluated for TYMS gene copy number. There were no patients with complete or partial response in the TYMS amplified group. RR and DCR were lower in the TYMS amplified group compared with the TYMS unamplified group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS were reduced in the TYMS amplified group. The analysis of TYMS gene copy number had higher sensitivity and specificity compared with TYMS protein expression (76.2 versus 50.0 %, 75.0 versus 66.7 %). CONCLUSION: The analysis of TYMS gene copy number is more suitable than TYMS protein expression for assessment of TYMS expression. TYMS gene amplification predicts outcome of patients receiving PMT with advanced NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Amplificación de Genes , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/administración & dosificación , Timidilato Sintasa/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Dosificación de Gen , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a consecutive series of elderly patients with primary central nervous system lymphoma (PCNSL) treated with single-agent pemetrexed without radiotherapy or intrathecal chemotherapy. METHODS: Twelve histologically confirmed newly diagnosed PCNSL patients older than 65 years were studied between 2008 and 2013. An induction chemotherapy was initially given (pemetrexed 600 mg/m(2) on day 1, every 3 weeks). Patients achieving a complete, partial response or stable disease proceeded to a maintenance phase (up to 6 cycles). Patients with progressive/recurrent disease (PD) were treated with whole brain radiotherapy on an individual basis. RESULTS: Four patients presented complete response, six patients showed partial response and two patients presented progressive disease. The median progression-free survival (PFS) was 9.0 months [95 % confidence interval (CI) 2.0-45.3] and the median overall survival was 19.5 months (95 % CI 5.0-45.3). Adverse events included leukocytopenia, anemia, fatigue, rash and vomiting. No neurotoxicity or treatment-related death was observed. The estimated 1-year and 2-year survival rate was 66.7 and 41.7 %, respectively. CONCLUSIONS: Our efficacy results demonstrate that the single-agent pemetrexed was feasible, active and well tolerated in elderly patients with PCNSL. Furthermore, this single-agent regimen results in higher response rates and less toxicity comparable with other chemotherapy or radiotherapy regimens. Prospectively, controlled studies are warranted to confirm such results.
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Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Pemetrexed/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma/mortalidad , Masculino , Estudios RetrospectivosRESUMEN
Em adultos os carcinomas tímicos representam cerca de 20% das neoplasias mediastinais. A maioria dos pacientes tem entre 40 e 60 anos de idade e há ligeira predominância do sexo masculino. Em função da raridade da doença não há ensaios clínicos randomizados realizados para orientar a escolha do tratamento na doença metastática refratária ou recorrente. Alguns regimes de segunda linha têm sido usados, a maioria baseada em cisplatina. Como linhas alternativas as opções são pemetrexed, 5-flourouracil associado a leucovorin, gemcitabina, capecitabina e paclitaxel, todas com taxas de resposta pequenas. Relatamos neste artigo um caso de carcinoma tímico tratado com pemetrexed e octreotide com resposta prolongada ao tratamento.