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1.
BMC Cancer ; 18(1): 241, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499653

RESUMO

BACKGROUND: Preclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Eligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC. The patients received 4 cycles of docetaxel (60 mg/m2), cisplatin (80 mg/m2), and bevacizumab (15 mg/kg) once every 3 weeks, followed by bevacizumab as maintenance therapy, every 3 weeks until disease progression or attainment of unacceptable toxicity level. The primary endpoint was objective response rate (ORR). The numbers of circulating endothelial cells (CEC) were also estimated on days 1 and 8 of the first cycle for the exploratory analysis of efficacy prediction. RESULTS: A total of 47 patients were enrolled from October 2010 to April 2012. Bevacizumab as maintenance therapy was administered to 41 patients (87.2%), and the median number of total treatment cycles was 9 (range: 1-36). ORR, median progression-free survival (PFS), and median overall survival of the patients were 74.5%, 9.0 months, and 27.5 months, respectively. The most common grade 3/4 adverse event was neutropenia (95.7%), followed by leukopenia (59.6%) and hypertension (46.8%). PFS was longer in patients with ≥10 count increase in CECs than that in patients with < 10 count increase in CECs (respective median PFS of 11.0 months versus 6.90 months) although the difference was not statistically significant (p = 0.074). CONCLUSIONS: A combination therapy of bevacizumab, cisplatin, and docetaxel, followed by bevacizumab as maintenance was highly effective in patients with non-squamous NSCLC despite the high incidence of grade 3/4 neutropenia. The increase in CEC count between days 1 and 8 may predict the efficacy of our bevacizumab-contained treatment regimen. TRIAL REGISTRATION: UMIN Clinical Trial Registry; UMIN000004368 . Registered date; October 11, 2010 (Retrospectively registered).


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Células Endoteliais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Células Neoplásicas Circulantes/patologia , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Docetaxel , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
2.
Oncology ; 92(5): 283-290, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28222447

RESUMO

BACKGROUND: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs. METHODS: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time. RESULTS: PD-L1 expression was significantly higher in tumors from men or current smokers. Squamous cell carcinoma histology was independently associated with high PD-L1 expression according to multivariate analysis (p = 0.015). The 5-year survival rate of patients was 70%, and the difference in the 5-year survival rate according to PD-L1 expression was not statistically significant (high expression group [67%] vs. low expression group [68%]); however, the squamous cell carcinoma group exhibited significantly lower 5-year survival rates as compared to the non-squamous cell carcinoma group (53 and 71%, respectively; p = 0.026). CONCLUSION: Here, we revealed high PD-L1 expression and poor prognosis observed in patients with surgically resected squamous NSCLC as compared with non-squamous NSCLC. Our results support the identification of patient subsets that most likely respond to anti-PD-1 therapy as the first step in precision medicine.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Anticorpos Monoclonais , Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
3.
Kansenshogaku Zasshi ; 89(2): 265-9, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-26552124

RESUMO

We report herein on a case strongly suspected of being pulmonary toxocariasis. A 22-year-old Indonesian man referred to our hospital presented with abnormal chest shadows upon medical examination. He had no symptoms. He did not have any pets nor did he eat raw beef or chicken. Hematological examination revealed eosinophilia and elevation of IgE. Chest computed tomography revealed 3 pulmonary nodules with the halo sign. We suspected a parasite infection and performed antiparasite antibody testing. Ascaris suum was slightly positive on the screening test. As specific antibody against the larval excretory-secretory products of Toxocara canis, measured at the National Institute of Infectious Diseases, was positive (level 3 up to 8). Subsequently, the abnormal chest shadows disappeared. However, two months later, 2 pulmonary nodules with the halo sign reappeared in other places. Diagnostic therapy with albendazole was performed for 8 weeks. Mild hepatic impairment emerged during therapy, but it was within the allowed range. Thereafter, the results improved for the imaging findings, eosinophilia, serum IgE level, and specific antibody. The antibody level became negative two months after the treatment had ended. We should consider toxocariasis in the differential diagnosis of migratory nodular shadows with the halo sign on chest computed tomography, and immunoserological testing is useful for the diagnosis.


Assuntos
Pneumopatias Parasitárias/diagnóstico , Toxocara canis , Toxocaríase/diagnóstico , Animais , Humanos , Pneumopatias Parasitárias/diagnóstico por imagem , Masculino , Radiografia , Toxocaríase/diagnóstico por imagem , Adulto Jovem
4.
Kansenshogaku Zasshi ; 89(1): 56-61, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-26548298

RESUMO

Pseudomonas aeruginosa is a significant causative bacterium in hospital-acquired pneumonia and nursing and healthcare-associated pneumonia, but it seems to be rare in community-acquired pneumonia (CAP). We report two cases of severe CAP due to P. aeruginosa. Case 1: A 52-year-old man was referred to our hospital for chest and back pain. He was being treated for diabetes mellitus and had a long history of smoking. Chest images showed consolidation in the right upper lobe. Soon after hospitalization, he developed sepsis shock and died seven hours later. Case 2: A 73-year-old man with a history of heavy smoking was referred to our hospital for right chest pain. Chest images showed right upper lobe pneumonia. Although wide-spectrum antimicrobial agents were administrated, he died ten hours after admission. In both cases, there was a rapid progression to death, despite administration of a broad spectrum of antibiotics and treatment for sepsis. In cases of CAP involving the right upper lobe, the possibility of bacteremia and rapid progress should be considered.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Resultado do Tratamento
5.
Oncology ; 87(4): 215-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25034225

RESUMO

BACKGROUND: Exon 19 deletion and L858R point mutation of the epidermal growth factor receptor (EGFR) are the most commonly encountered EGFR mutations in non-small cell lung cancer (NSCLC), and predict higher clinical outcomes following treatment with gefitinib. The objective of this study was to evaluate the differential clinical outcomes of gefitinib in patients with NSCLC according to the type of active EGFR mutation, i.e. exon 19 deletion or L858R point mutation. METHODS: We identified patients with advanced NSCLC harboring the exon 19 deletion or the L858R point mutation of EGFR who were on gefitinib treatment. The clinical outcomes were evaluated. RESULTS: Of the 124 patients with NSCLC harboring active EGFR mutations, the overall response rate, progression-free survival and overall survival were 60.5%, 11.3 and 27.3 months, respectively, and did not differ significantly between patients with the exon 19 deletion (61.8%, 11.3 and 32.2 months, respectively) and those with the L858R point mutation (58.9%, 9.0 and 27.7 months, respectively). CONCLUSION: It may be considered that there is no difference in the clinical efficacy of gefitinib between NSCLC patients who harbor the exon 19 deletion and those with the L858R point mutation.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação Puntual , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Éxons , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Deleção de Sequência , Resultado do Tratamento
6.
Chemotherapy ; 59(2): 99-105, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24021914

RESUMO

BACKGROUND: Currently, there are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy of amrubicin monotherapy as a salvage treatment in heavily pretreated NSCLC patients. METHODS: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at a Kitasato University Hospital between January 2009 and December 2012 were retrospectively reviewed. Amrubicin was administered to patients by intravenous injection at a dose of 35 or 40 mg/m(2) daily on 3 consecutive days, and cycles were repeated at 3-week intervals. RESULTS: There were 36 patients who met the inclusion criteria. Their median number of prior chemotherapy treatments was 4 (range 2-7), and the median number of chemotherapy cycles per patient was 4 (range 1-9). Grade 3 or 4 hematologic toxicities included neutropenia (61.1%), leukopenia (58.3%), thrombocytopenia (22.2%) and anemia (11.1%). Febrile neutropenia occurred in 8 patients (22.2%). Nonhematologic toxicities were mild. The overall response rate, median progression-free survival time and median survival time were 8.3%, 1.7 months, and 6.3 months, respectively. Progression-free survival time was the same, i.e. 1.7 months in both groups i.e. the 35- and the 40-mg/m(2)-dose groups. CONCLUSION: Amrubicin exhibits modest activity and acceptable toxicity when used as a third or later line of chemotherapy for advanced NSCLC.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Doenças Hematológicas/etiologia , Humanos , Injeções Intravenosas , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Gan To Kagaku Ryoho ; 40(3): 375-7, 2013 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-23507602

RESUMO

A 68-year-old man was referred to our hospital because of an abnormal chest shadow. Adenocarcinoma was detected using percutaneous needle aspiration cytology from the left supraclavicular lymph node. The patient was diagnosed as having primary adenocarcinoma of the lung(cT1bN3M1b: BRA OSS). Exon 18G 719X and exon 20 T790M mutations of the EGFR gene were detected in the same specimen. For first-line chemotherapy, four courses of cisplatin plus docetaxel were used. The primary lesion and a brain metastasis were reduced after the first-line chemotherapy. About four months later, he developed a recurrent brain metastasis and leptomeningeal carcinomatosis. He was treated with erlotinib(150mg/day)after wholebrain irradiation. The leptomeningeal carcinomatosis findings on a head CT image and the patient's consciousness disorder improved after treatment. EGFR-TKI therapy was effective in a case with leptomeningeal carcinomatosis, and coexisting EGFRsensitive and EGFR-resistant mutations.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinomatose Meníngea/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Biópsia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Cloridrato de Erlotinib , Humanos , Neoplasias Pulmonares/patologia , Masculino , Carcinomatose Meníngea/genética , Carcinomatose Meníngea/secundário
8.
Chemotherapy ; 58(4): 313-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23147191

RESUMO

The purpose of this study was to evaluate the efficacy of pemetrexed monotherapy in previously treated patients with advanced non-small cell lung cancer (NSCLC) including salvage treatment, and to evaluate whether thymidylate synthase (TS) expression is a predictor for pemetrexed efficacy. Hundred and four previously treated patients with advanced NSCLC who received pemetrexed monotherapy were retrospectively evaluated for clinical efficacy and toxicity. If available, tissue specimens of patients were also analyzed immunohistochemically for TS expression. The patients' median age was 65 years (range: 43-82). An overall response rate of 9.6% and a median progression-free survival (PFS) time of 3.4 months were achieved. The response rates for the second-line, third-line, fourth-line or further treatments were 9.1, 9.3 and 10.2% (p = 0.33); the median PFS were 3.3, 3.2 and 3.8 months (p = 0.21). The median follow-up duration was 14.9 months; the median overall survival (OS) was 11.9 months. The median PFS and OS were significantly longer in the TS-negative group than in the TS-positive group (5.8 months vs. 1.6 months; p = 0.03, and 14.7 months vs. 8.6 months; p = 0.04, respectively). Pemetrexed monotherapy could be considered as an option in the fourth or later lines of treatment of previously treated patients with advanced NSCLC as well as a second- or third-line treatment, and TS expression may be a potentially predictive factor for pemetrexed efficacy in NSCLC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Timidilato Sintase/metabolismo , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Ácido Fólico/uso terapêutico , Glutamatos/efeitos adversos , Guanina/efeitos adversos , Guanina/uso terapêutico , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Leucopenia/etiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Neutropenia/etiologia , Pemetrexede , Terapia de Salvação , Trombocitopenia/etiologia , Resultado do Tratamento
9.
Gan To Kagaku Ryoho ; 39(13): 2509-12, 2012 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-23235169

RESUMO

BACKGROUND: There have been few reports on the efficacy or safety of combination therapy with carboplatin-paclitaxel plus bevacizumab(TC+Bev)in previously treated patients with non-small cell lung carcinoma(NSCLC). PURPOSE: The objective of this study was to assess the efficacy and safety of TC+Bev as second-line therapy and beyond for previously treated NSCLC patients. METHODS: A total of 17 patients previously treated with NSCLC at the Kitasato University Hospital between April 2010 and February 2012 were enrolled in this retrospective study. On day 1 all patients received a 200mg/m2 dose of paclitaxel by intravenous infusion over a 3-h period, followed by infusion of carboplatin at a dose corresponding to an AUC of 6.0 min mg/mL, and then by Bev at a dose of 15mg/m2. The treatment course was repeated every three or four weeks. Patients continued to receive Bev monotherapy every 3 weeks thereafter until evidence of disease progression or unacceptable toxicity developed. RESULTS: Median age: 60 years old(range 39-74 years old); gender: male/female, 6/11; PS 0-1/≥2, 17/0; clinical stage:III B/IV postoperative recurrence, 0/16/1; EGFR mutation status: positive/negative/unknown, 7/9/1; histological type: adenocarcinoma in all patients; median number of prior regimens: 3. 4(1-6); median number of cycles(induction phase): 3(1-6). The objective response rate and disease control rate were 17. 6% and 70. 6%, respectively, and the median progression-free survival time was 4. 7 months. There were no treatment-related deaths, and the toxicities of the treatment regimen were acceptable. CONCLUSION: TC+Bev therapy exhibits activity in previously treated NSCLC patients and has acceptable toxicity. Further study is warranted to confirm our results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação
10.
Gan To Kagaku Ryoho ; 39(1): 59-62, 2012 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-22241352

RESUMO

BACKGROUND: In Japan, the standard first-line therapy for elderly patients with advanced non-small lung cancer(NSCLC)is docetaxel(DOC)monotherapy. However, there is very limited information about second-line and beyond chemotherapy regimens for elderly patients with advanced NSCLC. Pemetrexed(PEM)monotherapy has been recognized as a standard regimen for advanced NSCLC in second-line settings, just as DOC monotherapy has been. PURPOSE: The objective of this study was to examine the efficacy and safety of PEM as second-line therapy and beyond for elderly patients. METHODS: The records of previously -treated elderly patients with advanced NSCLC, who had been treated with PEM as second-line therapy and beyond between July 2009 and December 2010, were retrospectively reviewed. RESULTS: median age: 73 years old(range 70-79 years old); gender: male/female, 11/8; PS 0-1/≥2, 19/0; clinical stage: III B/IV/postoperative recurrence, 4/10/5; pathology: adeno/LCNEC/other, 17/1/1 patient. The objective response-rate and disease control-rate were 15. 8% and 57. 9%, respectively. Median progression-free survival time was 3. 2 months. There were no treatment-related deaths, and most of the toxicities of the treatment regimen were mild and acceptable. CONCLUSION: PEM monotherapy exhibits activity in previously treated elderly NSCLC patients and has an acceptably low toxicity. Further study is warranted to confirm our results.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Guanina/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pemetrexede , Terapia de Salvação
11.
Nihon Kokyuki Gakkai Zasshi ; 49(7): 523-7, 2011 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-21842690

RESUMO

A 64-year-old man, who had been treated with valsartan for hypertension since about 2 months previously, was admitted with exertional dyspnea. A chest X-ray film on admission showed infiltrative shadows in bilateral lower lung fields. Chest computed tomographic images showed diffuse ground-glass opacities, consolidation and traction bronchiectasis. His serum KL-6 level was markedly elevated, to 7,360 U/ml. Despite the withdrawal of valsartan, his symptoms deteriorated, and a drug lymphocyte stimulation test was positive for valsartan. Based on these findings, we diagnosed valsartan-induced pneumonitis. Glucocorticoids were administered, and his symptoms, chest radiograph findings and serum KL-6 level all improved. Currently, angiotensin II receptor blockers (ARBs), including valsartan, are often used as the first drug of choice to treat hypertension, but they can cause drug-induced pneumonitis. It has been previously reported that serum KL-6 levels may reflect the clinical activity of drug-induced pneumonitis. In cases of drug-induced pneumonitis with a high level of serum KL-6, glucocorticolds should be started at an early stage.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Mucina-1/sangue , Pneumonia/induzido quimicamente , Tetrazóis/efeitos adversos , Valina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Valina/efeitos adversos , Valsartana
12.
Nihon Kokyuki Gakkai Zasshi ; 49(11): 843-7, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22171489

RESUMO

A 68-year-old woman was admitted to our institution's respiratory section because of dyspnea on effort in January, 2007. She had previously received a diagnosis of Sjögren's syndrome because of dryness in her eyes in 1991. Chest radiography and chest CT in 2001 revealed diffuse multiple cystic lesions in both lungs which had progressed gradually for 6 years. Biopsy specimens obtained by video-assisted thoracoscopy showed lymphoid hyperplasia with follicular bronchiolitis and lymphocytic alveolitis. Narrowing of the small airways and obstructive lung disease with multiple bullae were observed and we suspected them to be related to peribronchiolar lymphocytic infiltration. These were lung involvements associated with Sjögren's syndrome. The patient's cystic lesions gradually worsened despite the administration of corticosteroid and cyclophosphamide. Cystic lesions in Sjögren's syndrome may be a treatment-resistant finding.


Assuntos
Cistos/etiologia , Pneumopatias/etiologia , Síndrome de Sjogren/complicações , Idoso , Feminino , Humanos
13.
Int J Clin Oncol ; 15(5): 447-52, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20464623

RESUMO

BACKGROUND: This study was conducted to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly and poor-risk patients with extensive-disease small-cell lung cancer (ED-SCLC). METHODS: Untreated SCLC patients who were >75 years of age or had a performance status of 2 or more were eligible. Amrubicin (35 or 40 mg/m(2) on days 1-3 every 3 weeks) was administered. RESULTS: Between January 2003 and May 2009, 27 patients were evaluated. The median number of treatment cycles was 4 (1-6). Grade 3 or 4 hematologic toxicities comprised neutropenia (63%), leukopenia (56%), thrombocytopenia (15%), and anemia (19%). Febrile neutropenia was observed in four (15%) patients. No treatment-related deaths occurred. The nonhematologic toxicities were mild. The overall response rate was 70%. Progression-free survival, median survival time, and the 1-year survival rate were 6.6 months, 9.3 months, and 30%, respectively. The 40 mg/m(2) dose was feasible and had a tendency to be more effective than the 35 mg/m(2) dose. CONCLUSIONS: Amrubicin exhibits activity and acceptable toxicities for elderly and poor-risk patients with ED-SCLC in the first-line treatment setting.


Assuntos
Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
14.
Gan To Kagaku Ryoho ; 37(11): 2161-3, 2010 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-21084818

RESUMO

A 56-year-old man was admitted to our hospital because of increasing chest discomfort and abnormal chest shadow. Computed tomography (CT) of the chest revealed an anterior mediastinal mass, pleural dissemination and lung metastasis. Percutaneus needle biopsy guided by CT showed that the mass was advanced thymic cancer (stage IV b according to the classification proposed by Masaoka). After failure of combination chemotherapy of cisplatin, vincristine, doxorubicin and etoposide (CODE), he received 4 cycles of carboplatin plus paclitaxel and then achieved confirmed stable disease. In terms of toxicity profile, grade 4 anemia, grade 2 leucopenia and neutropenia were observed, and particularly non-severe toxicity was not observed in terms of non-hematologic toxicity. Carboplatin plus paclitaxel can be an active agent against pretreated thymic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Timo/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
15.
Int J Clin Oncol ; 14(4): 332-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19705244

RESUMO

BACKGROUND: Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib. METHODS: We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records. RESULTS: Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100). CONCLUSION: As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.


Assuntos
Anticoagulantes/uso terapêutico , Antineoplásicos/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Varfarina/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/secundário , Interações Medicamentosas , Feminino , Gefitinibe , Humanos , Coeficiente Internacional Normatizado , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Tempo de Protrombina , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Varfarina/efeitos adversos
16.
Oncol Rep ; 20(4): 727-30, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18813810

RESUMO

One of the dose-limiting toxicities of irinotecan (CPT-11) is delayed-onset diarrhea, which is the greatest barrier to treatment with CPT-11-containing regimens. CPT-11 is converted to its active metabolite, SN-38, which is conjugated by hepatic uridine diphosphate glucuronosyl transferase to SN-38 glucuronide (SN-38G). SN-38G, once excreted in the intestinal lumen via bile, is extensively deconjugated by bacterial beta-glucuronidase with the regeneration of SN-38 in the intestinal lumen, which may cause diarrhea. However, the metabolism of CPT-11 and its metabolites by intestinal microflora are yet to be reported. This study was carried out to investigate the microbial transformation of CPT-11 and SN-38 using an anaerobic mixed culture of rat cecal microorganisms. No reaction in the mixed cultures was observed when CPT-11 or SN-38 lactone was added to the culture medium. When CPT-11 was added to the culture broth, a significant amount of water-soluble CPT-11 was detected in the spent culture medium. In contrast, only a slight amount of SN-38 was found in the supernatant when SN-38 lactone was added to the broth. A significant quantity of SN-38 was found in the sediment. In conclusion, these results strongly suggest that SN-38 produced from SN-38G by the action of bacterial beta-glucuronidase is rapidly adsorbed by the intestinal bacterial cell walls in the sediment because of the hydrophobic and lipophilic nature of SN-38, and a small amount of SN-38 remains in the intestinal luminal fluid. Thus, we need to reconsider the role of SN-38 in the intestinal lumen in CPT-11-induced late-onset diarrhea.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Bactérias/metabolismo , Camptotecina/análogos & derivados , Intestinos/microbiologia , Animais , Camptotecina/efeitos adversos , Camptotecina/metabolismo , Diarreia/induzido quimicamente , Irinotecano , Masculino , Ratos , Ratos Wistar
17.
Hum Pathol ; 74: 148-155, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29320753

RESUMO

To discover novel tumor markers for lung adenocarcinoma (AC), we performed proteomics analysis and reported a correlation between S100A16 membranous expression in AC tissues and a poor prognosis. However, some patients with a good prognosis also showed S100A16 membranous staining. We re-evaluated immunohistochemically stained tissues, and found membrane-positive and nucleus-negative expressions to be significantly higher in the presence of the following: male, smoker, positive nodal metastasis, higher p-TNM stage, larger tumor, poorer differentiation, positive for lymphatic invasion, positive for vascular invasion, and positive for pleural invasion (all factors P < .05). This pattern of staining was also an independent prognostic factor. Furthermore, we analyzed S100A16 mRNA expression using TCGA and Kaplan-Meier plotter databases, and found that higher S100A16 mRNA expression in AC was significantly correlated with poorer survival. To our knowledge, there has been no comprehensive study focused on both S100A16 protein and mRNA expression levels in AC patients. Our results suggest that the subcellular localization of S100A16 and S100A16 mRNA expression levels is a promising prognostic marker for AC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Metástase Linfática/patologia , Proteínas S100/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Idoso , Biomarcadores Tumorais , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Fatores Sexuais , Fumar , Taxa de Sobrevida
18.
Case Rep Oncol ; 10(1): 333-338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28559816

RESUMO

Pazopanib, a multitargeting tyrosine kinase inhibitor, has single-agent activity in patients with advanced soft-tissue sarcoma. Herein, we describe 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft-tissue sarcoma. These 2 patients had multiple lung metastases. According to previous reports and our past experience, the risk of pneumothorax may be higher in patients with multiple lung metastases. Although a causal relationship is uncertain, the risk of pneumothorax when prescribing pazopanib for these patients should be considered.

19.
Oncol Res Treat ; 40(10): 594-602, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28950283

RESUMO

BACKGROUND: Several studies have reported that S100A14 plays important roles during different steps of the tumorigenic process and tumor progression of several types of cancer. The aim of the present study was to investigate the clinicopathological and prognostic significance and functional roles of S100A14 in lung adenocarcinoma. PATIENTS AND METHODS: S100A14 expression was immunohistochemically studied in 166 consecutive resected lung adenocarcinomas, and its correlation with clinicopathological parameters was evaluated. Functional roles of S100A14 in lung adenocarcinoma were investigated based on invasion and migration assays on a small interfering (si)RNA-treated lung adenocarcinoma cell line. RESULTS: S100A14 expression was detected in 82 of the 166 (49.4%) lung adenocarcinomas. S100A14 expression was significantly correlated with sex, poorer tumor differentiation, higher disease stages, larger tumor size, lymph node metastasis, intratumoral vascular invasion, intratumoral lymphatic invasion, pleural invasion, and poorer prognosis. Invasion and wound healing assays showed that S100A14 siRNA knockdown cells had significantly decreased invasion and migration abilities compared with siRNA control cells. CONCLUSION: S100A14 is expressed in a subset of lung adenocarcinoma, and its expression is related to certain clinicopathological parameters. Furthermore, S100A14 expression was strongly correlated with migration and invasion in lung adenocarcinoma cells.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas de Ligação ao Cálcio/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adenocarcinoma/mortalidade , Idoso , Linhagem Celular Tumoral , Membrana Celular/patologia , Movimento Celular/genética , Estudos de Coortes , Citoplasma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes/patologia , Prognóstico , RNA Interferente Pequeno/genética , Estudos Retrospectivos
20.
Onco Targets Ther ; 10: 5273-5279, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29138580

RESUMO

PURPOSE: Although cisplatin-based adjuvant chemotherapy improves the survival of patients with resected non-small-cell lung cancer, not all patients show a survival benefit, and some patients experience severe toxicity. Therefore, identifying biomarkers is important for selecting subgroups of patients who may show improved survival with platinum-based adjuvant chemotherapy. S100A16 is thought to play key roles during different steps of tumor progression. The aim of this study was to evaluate the use of S100A16 expression as a prognostic marker in patients with completely resected lung adenocarcinoma receiving platinum-based adjuvant chemotherapy. METHODS: S100A16 expression was immunohistochemically studied in 65 consecutive lung adenocarcinoma patients who underwent complete resection and received platinum-based adjuvant chemotherapy. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A16 expression on disease-free survival (DFS) and overall survival (OS). RESULTS: S100A16 expression was detected in 26 of the 65 (40.0%) lung adenocarcinoma patients. Although S100A16 expression was not correlated with DFS (P=0.062), it was significantly correlated with OS (P=0.009). In addition, multivariable analysis revealed that S100A16 expression independently predicted a poorer survival (HR =4.79; 95% CI =1.87-12.23; P=0.001). CONCLUSION: The present study revealed that S100A16 is a promising candidate as a prognostic marker for platinum-based adjuvant chemotherapy in resected lung adenocarcinoma. A further large-scale study is needed to confirm the present results.

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