RESUMO
BACKGROUND: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. RESULTS: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.
Assuntos
Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pemetrexede , Taxa de SobrevidaRESUMO
A novel vasorelaxant peptide, adrenomedullin (AM), has been isolated from the acid extract of human pheochromocytoma. We have recently shown that AM inhibits histamine- and acetylcholine-induced bronchoconstriction in anesthetized guinea pigs in vivo, and this bronchodilatory effect is long-lasting. Here, we measured plasma AM concentrations in nine patients with an acute attack of bronchial asthma. The results were compared with values in 30 age-matched normal control subjects and seven age-matched stable asthmatic patients. The mean AM concentrations of patients with an acute asthma attack (98 +/- 22 pg/mL) were clearly higher than those of normal control subjects (18 +/- 2 pg/mL) and stable asthmatic patients (21 +/- 3 pg/mL). Reverse-phase high-performance liquid chromatography (HPLC) showed that the major component of plasma immunoreactive AM in patients with an asthma attack and in normal subjects equally corresponded to authentic human AM(1-52). Our results suggest that plasma AM is markedly increased in many of the patients during an acute attack of bronchial asthma, but it is not observed in stable asthmatic patients. Although this report is preliminary, the observed increase of circulating AM during an acute asthma attack may represent a compensatory mechanism against the bronchoconstriction, probably through its bronchodilatory action.
Assuntos
Asma/sangue , Peptídeos/sangue , Vasodilatadores/sangue , Doença Aguda , Adrenomedulina , Adulto , Idoso , Humanos , Pessoa de Meia-IdadeRESUMO
A 79-year-old female presented with persistent dry cough, and a chest radiograph showed a mass shadow in the right upper lung. Bronchoscopic examination revealed that the right main bronchus was severely obstructed by a polypoid tumor, which was diagnosed pathologically as squamous papilloma. After the failure of the attempted endobronchial snare to remove the tumor, right upper lobectomy was performed. The polymerase chain reaction (PCR) examination showed the presence of human papilloma virus type 11 DNA in the resected tumor, suggesting that this virus was the cause of this solitary squamous papilloma of the lung.
Assuntos
Neoplasias Brônquicas/virologia , Papiloma/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Idoso , Neoplasias Brônquicas/diagnóstico , Broncoscopia , Feminino , Humanos , Papiloma/diagnóstico , Reação em Cadeia da PolimeraseRESUMO
A 67-year-old man presented with dyspnea on exertion. Bronchoscopic examination revealed a tumor arising from the middle portion of the trachea and extending to the right main bronchus. The pathological diagnosis was adenoid cystic carcinoma. Radiotherapy and subsequent endobronchial electrocautery were performed, and elicited a partial response. In the clinical course. Dumon and Ultraflex stents were placed in the trachea asynchronically. Brachytherapy and esophageal stent placement were also performed for tumor control in the trachea and esophagus. Autopsy revealed that the tumor had invaded the trachea and esophagus, and bacterial mediastinitis was also demonstrated. Because the tumor was successfully controlled during the following 4 years and 9 months, we concluded that endobronchial therapy such as stent placement or electrocautery is useful for maintaining good quality of life.
Assuntos
Carcinoma Adenoide Cístico/terapia , Qualidade de Vida , Neoplasias da Traqueia/terapia , Idoso , Braquiterapia , Broncoscopia , Carcinoma Adenoide Cístico/patologia , Terapia Combinada , Eletrocoagulação , Humanos , Masculino , Stents , Neoplasias da Traqueia/patologiaRESUMO
Photodynamic therapy (PDT) in early squamous cell carcinoma of the bronchus has been shown to result in complete response (CR) and cure. However, local recurrence after PDT develops frequently even after complete remission. Because the effect of PDT had been reported to depend on apoptosis, and apoptosis is inhibited by bcl-2 protein, the relationship between the expression of bcl-2 protein and local recurrence after PDT was examined immunohistochemically. From 1983 to 1997, 50 patients with 59 early squamous cell carcinoma of the bronchus received PDT, and a CR was obtained in 43 lesions (72.8%). As there was no recurrence among tumours that were disease-free for more than 2 years, in this study the tumours were defined as cured when recurrence did not occur 2 years subsequent to the receiving of PDT. Of these CR lesions, 31 carcinomas (53.4%) resulted in a cure. Bcl-2 immunoreactivity was detected in 23 tumours (46.9%) and p53 immunoreactivity was detected in 22 tumours (44.9%). When all tumours were divided into either a large tumour with a longitudinal tumour length of 10 mm or more, or a small tumour with a length of less than 10 mm, the large tumour expressed more bcl-2 protein than the small tumour (P = 0.0155). The degree of bcl-2 expression was significantly related with tumour size (P = 0.0155). The expression of bcl-2 and p53 protein was not associated with the cure rate due to PDT. Tumour length and T status in TNM staging were significantly related to the cure by univariate analysis. T status was the only predictor of the cure according to mutivariate analysis. Of 42 CR lesions, the expression of neither bcl-2 nor p53 protein was associated with local recurrence; only T status was significantly associated (P = 0.008). The relationship between the expression of oncoprotein and local recurrence after PDT was not documented in this study. The success of PDT may depend on the exact assessment of tumour size under optimized PDT illumination.
Assuntos
Neoplasias Brônquicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares , Fotoquimioterapia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Idoso , Neoplasias Brônquicas/química , Neoplasias Brônquicas/genética , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/genética , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análiseRESUMO
A 54-year-old man was referred to our hospital because of hemoptysis. Fiberoptic bronchoscopy revealed irregular mucosa of the right B1, B2, B3, B8, B9, and B10, and the left B1+2 and B3. Bronchoscopic and histological findings indicated bronchial varices.
Assuntos
Brônquios/irrigação sanguínea , Varizes/patologia , Broncoscopia , Hemoptise/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Varizes/complicaçõesRESUMO
BACKGROUND: To determine the efficacy, toxicity and pharmacokinetics of intrapleural cisplatin (CDDP) and etoposide as a treatment for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC). METHODS: Seventy patients with MPE associated with NSCLC were enrolled in this study. In 68 patients, a catheter was inserted into the pleural cavity, within 24 h after complete drainage of the pleural effusion, CDDP (80 mg/m2) and etoposide (80 mg/m2) were simultaneously administered successfully via the catheter and the catheter was clamped. Seventy-two hours later, the catheter was unclamped to allow drainage. The catheter was removed when the accumulated intrapleural fluid decreased to 20 ml or less per day. RESULTS: The pharmacokinetic profiles showed high maximum concentrations of CDDP (free form, 88 microg/ml) and etoposide (182. 4 microg/ml) in intrapleural fluids. CDDP did not remain for a long period (free form, beta-phase half-life = 10.51 h) in the fluids, while etoposide persisted for a long period (beta-phase half-life = 62.53 h). The overall response rate was 46.2%, the median survival time 32.3 weeks, the 1-year survival rate 28.7% and the 2-year survival rate 12.8%. The most serious adverse reactions were WHO grade 3 anemia (3 patients), grade 3 nausea and vomiting (17 patients), grade 3 constipation (1 patient), grade 3 pulmonary toxicity (1 patient), grade 4 fever (1 patient), grade 3 infection (1 patient) and grade 3 mental disorder (1 patient). CONCLUSION: Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/farmacocinética , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/farmacocinética , Feminino , Humanos , Injeções Intralesionais , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/mortalidade , Análise de SobrevidaRESUMO
We encountered a case of small-cell lung cancer in a patient with subacute sensory neuropathy that began 5 months before the cancer was diagnosed. A 60-year-old man complained of abnormalities in the functioning of his peripheral sensory systems (senses of pain, touch, position, and vibration). A chest X-ray film obtained on admission showed an anterior mediastinal tumor. The anti-Hu antibody was found in his serum. The diagnosis was small-cell lung cancer. Combination chemotherapy (cisplatin and irinotecan, CPT-11) was begun and the response was a complete remission. The symptoms of neuropathy continued. The anti-Hu antibody was useful in the diagnosis in the case of small-cell lung cancer combined with subacute sensory neuropathy.
Assuntos
Anticorpos Anti-Idiotípicos/análise , Autoanticorpos/análise , Biomarcadores Tumorais/análise , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Humanos , Irinotecano , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiossensibilizantes/uso terapêutico , Animais , Camptotecina/uso terapêutico , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irinotecano , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dosagem RadioterapêuticaRESUMO
A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, surgically unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled. Irinotecan was administered as a 90 min intravenous infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose escalation was done in 15 mg m(-2) increments. Dose-limiting toxicity was defined as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or grade 4 haematologic toxicity according to the WHO criteria. Radiation was delivered to the primary tumour and regional lymph nodes (40 Gy), followed by a boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six eligible patients were evaluated for toxic effects and clinical outcome. Severe oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of the five patients given 60 mg m(-2) developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 45 mg m(-2) in the phase II study. The objective response rate was 76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose-limiting toxicities of weekly irinotecan combined with thoracic irradiation. The maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(-2) wk(-1), respectively. This combined therapy for locally advanced non-small cell lung cancer is promising and shows acceptable toxicity.