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BACKGROUND: Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) targeting ALK and ROS1. The Barossa study is a multicenter, phase II basket study of brigatinib in patients with ROS1-rearranged solid tumors. ROS1 TKI-naive patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) were enrolled in cohort 1, and ROS1-rearranged NSCLC patients treated previously with crizotinib were enrolled in cohort 2. Patients with ROS1-rearranged solid tumors other than NSCLC were enrolled in cohort 3. PATIENTS AND METHODS: Eligible patients received brigatinib at the dose of 180 mg once daily with a 7-day lead-in period at 90 mg. The primary endpoint was the objective response rate (RECIST 1.1) assessed by independent central review in cohorts 1 and 2. RESULTS: Between July 2019 and June 2021, 51 patients were enrolled into the study. Of the 51, 47 patients had ROS1-rearranged NSCLC; 28 and 19 of these patients were enrolled in cohort 1 and cohort 2, respectively. The remaining four patients had other ROS1-rearranged solid tumors, including rectal, brain, and pancreas tumor in one patient each, and primary unknown tumor in one patient. The confirmed objective response rate was 71.4% [95% confidence interval (CI) 51.3% to 86.8%] in cohort 1 (TKI-naive NSCLC patients) and 31.6% (95% CI 12.6% to 56.6%) in cohort 2 (NSCLC patients treated previously with crizotinib). The median progression-free survival was 12.0 months (95% CI 5.5-22.9 months) in cohort 1 and 7.3 months (95% CI 1.3-17.5 months) in cohort 2. None of the patients in cohort 3 showed any treatment response. Pneumonitis was observed in 9.8% of all the patients. CONCLUSIONS: Brigatinib was effective in TKI-naive patients with ROS1-rearranged NSCLC. The safety profile of brigatinib was consistent with that reported from previous studies.
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BACKGROUND: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM). MATERIALS AND METHODS: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints. RESULTS: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity. CONCLUSIONS: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Gencitabina , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Cisplatino/uso terapêutico , Cisplatino/farmacologia , Cisplatino/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II-IIIA non-small cell lung cancer. METHODS: Patients received three cycles of docetaxel (60 mg m(-2)) plus cisplatin (80 mg m(-2)) and then received S-1 (40 mg m(-2) twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients. RESULTS: One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%). CONCLUSION: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Esquema de Medicação , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: We conducted a feasibility study of induction chemotherapy followed by gefitinib and thoracic radiotherapy (TRT) for unresectable locally advanced adenocarcinoma of the lung. PATIENTS AND METHODS: Patients received induction chemotherapy with cisplatin (80 mg/m(2), days 1 and 22) and vinorelbine (25 mg/m(2), days 1, 8, 22, and 29) followed by gefitinib (250 mg daily, beginning on day 43, for 1 year) and TRT (60 Gy/30 fractions, days 57-98). The primary end point was feasibility, which was defined as the proportion of patients who completed 60 Gy of TRT and received >75% of the planned dose of gefitinib without developing grade 2 or worse pneumonitis. RESULTS: Of the 38 enrolled patients, 23 patients [60.5% ; 80% confidence interval (CI) 48.8-71.3] completed treatment without experiencing grade 2 or worse pneumonitis. During the chemoradiation phase, grade 3-4 alanine aminotransferase elevations were observed in 37.1% of the patients. The overall response rate was 73.0% . The median survival time was 28.5 months (95% CI 22.5-38.2), and the 2-year survival rate was 65.4% . CONCLUSIONS: Although the results did not meet our criterion for feasibility, the toxicity was acceptable. This treatment warrants further evaluation among patients with locally advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução , Neoplasias Pulmonares/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cooperação do Paciente , Pneumonia/induzido quimicamente , Quinazolinas/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
BACKGROUND: The treatment of squamous cell carcinoma of the lung has not advanced sufficiently. Nedaplatin is a second-generation platinum compound that is active against squamous cell carcinoma of the lung, with a response rate of ~40%. PATIENTS AND METHODS: Eligible patients with advanced squamous cell carcinoma of the lung were treated with docetaxel (60 mg/m(2)) and nedaplatin (100 mg/m(2)) administered i.v. on day 1; these doses were determined in an earlier phase I study. The treatment cycles were repeated every 3 weeks. The primary end point was the response rate, and the secondary end points were overall survival, progression-free survival, and toxicity. RESULTS: Twenty-one patients were enrolled. Eighteen of the patients were male, and the median age was 67 years. The objective response rate was 62%. The median progression-free survival time was 7.4 months. The median survival time was 16.1 months, and the 1-year survival rate was 66.7% (95% confidence interval 46.5% to 86.8%). The most common adverse event was neutropenia (grade 3/4, 86%). Non-hematological toxic effects were relatively mild. One patient died of sepsis. CONCLUSIONS: Combination chemotherapy with nedaplatin and docetaxel is highly active and has an acceptable toxicity. Further investigation of nedaplatin and docetaxel is warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversosRESUMO
Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Carcinoma de Células Pequenas/patologia , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Irinotecano , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Terapia de Salvação , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
We conducted a prospective, randomized, double-blind, parallel study comparing the antiemetic activity and tolerability of treatment with droperidol (2.5 mg d.i.v. twice daily for 5 days) and placebo, both combined with granisetron (3 mg d.i.v. on the first day) and dexamethasone (16 mg d.i.v. on the first day, 8 mg d.i.v. on days 2, 3, and 4 mg d.i.v. on days 4, 5). A total of 180 lung cancer patients receiving high-dose cisplatin (80 mg/m(2))-containing chemotherapy were enrolled in the study, and 171 of them were capable of being evaluated. The clinical characteristics of the patients in the two treatment arms were well balanced. Complete protection from nausea and vomiting was recorded in the acute phase in 97% of patients who treated with droperidol versus 98% of patients who given the placebo (P=0.920), and in 42% versus 38% in the delayed phase (P=0.615). The multiple logistic regression analysis showed that a history of motion sickness was a significant risk factor for cisplatin-induced delayed emesis (odds ratio [OR]=5.98; 95% CI=2.15 to 16.7, P=0.0006). Droperidol-containing treatment was well tolerated by most patients, however, the incidence of sleepiness in the droperidol group was higher than in the placebo group (69% versus 30%, P<0.0001). In conclusion, our data did not support the hypothesis that addition of droperidol to granisetron and dexamethasone reduces the delayed emesis induced by high-dose cisplatin.
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Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Droperidol/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/mortalidade , Masculino , Segurança , Análise de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
We conducted a phase II trial of triplet chemotherapy consisting of vinorelbine, gemcitabine, and cisplatin in patients with advanced non-small cell lung cancer to assess its efficacy and toxicity. Thirty-three patients with chemotherapy-naïve stage IIIB disease (n=8), stage IV disease (n=23), or recurrence after surgical resection (n=2) were given intravenous infusions of vinorelbine 25 mg m(-2), gemcitabine 1000 mg m(-2), and cisplatin 40 mg m(-2) on days 1 and 8 at 3-week intervals. There were 16 partial responses, and the objective response rate was 48% (95% confidence interval: 31-66%). The median survival time was 13.5 months (95% confidence interval: 10.6-16.4 months), and the one-year survival rate was 61%. Grade 4 haematologic toxicity consisted of neutropenia in 72% of patients, and febrile neutropenia occurred in 42% of the patients. There was one toxic death, and it was attributed to neutropenic fever and haemoptysis. Autopsy revealed diffuse pulmonary haemorrhage secondary to bacterial abscesses and vasculitis in both lungs. The common nonhaematologic toxicities included grade 2-3 nausea (39%) and vomiting (18%). Triplet chemotherapy containing vinorelbine, gemcitabine, and cisplatin is effective in the treatment of chemo-näive patients with advanced non-small cell lung cancer, but produces unacceptable frequent febrile neutropenia.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Docetaxel , Relação Dose-Resposta a Droga , Feminino , Humanos , Ifosfamida/administração & dosagem , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivadosRESUMO
BACKGROUND: To determine the maximum tolerated dose and recommended dose of cisplatin and docetaxel administered by three consecutive weekly infusions in both non-elderly (< or =74 years) and elderly (> or =75 years) patients, we conducted two independent phase I studies for nonelderly and elderly patients with non-small cell lung cancer. METHODS: Between April 1998 and September 1999, 26 non-elderly (median, 54 years; range, 44-73 years) and 12 elderly (median, 76 years; range, 75-80 years) patients with non-small cell lung cancer were entered in these studies. The eligibility criteria of both cohorts were identical except for age. Chemotherapy consisted of cisplatin 25 mg/m2 and an escalated dose of docetaxel on days 1, 8 and 15 every 4 weeks. The initial dose of docetaxel was 20 mg/m2 and it was increased by 5 mg/m2 at each dose level. RESULTS: In the non-elderly and elderly cohorts, up to 45 or 25 mg/m2 of docetaxel, respectively, were administered. Dose-limiting toxicities were neutropenia, liver damage, pneumonia and omission of treatment on day 15 by leukopenia and refusal in the non-elderly cohort; pneumonia and omission of treatment on day 15 by refusal due to fatigue/asthenia or fever in the elderly cohort. We considered the recommended doses for phase II studies were cisplatin 25 mg/m2 and docetaxel 35 mg/m2 on days 1, 8 and 15 for non-elderly patients and cisplatin 25 mg/m2 and docetaxel 20 mg/m2 on days 1, 8 and 15 for elderly patients. Seven of 26 (27%) and seven of 12 (58%) patients achieved a partial response, median survival times were 8.7 and 7.2 months and 1 year survival rates were 27 and 27% in the non-elderly and elderly cohorts, respectively. CONCLUSIONS: Further evaluation of this combination chemotherapy is warranted for both nonelderly and elderly patients with non-small cell lung cancer but the dose of docetaxel should be lower for elderly than non-elderly patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Docetaxel , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Análise de SobrevidaRESUMO
Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA), and pro-gastrin-releasing peptide (proGRP) can be used as tumor markers for lung cancer. CEA is sensitive for adenocarcinoma, SCC and CYFRA for squamous cell carcinoma, and NSE and proGRP for small cell carcinoma. A tumor marker is generally used as a marker to monitor the clinical course. Serum levels of pro-GRP, reflect the disease course of patients with small cell lung cancer more accurately than NSE or CEA. Among the patients with clinical N0-1 non-small cell lung cancer high serum CEA levels, adenocarcinoma histology, and large tumor dimension were significant predictors of pathologic N2 disease. CEA played a new role in predicting metastasis to mediastinal lymph nodes A more effective treatment may enhance the value of tumor markers to predict relapse.
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Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/diagnóstico , Serpinas , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Humanos , Queratinas/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Fosfopiruvato Hidratase/sangue , Prognóstico , Proteínas Recombinantes/sangueRESUMO
Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) have been reported to be useful markers for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer (SCLC). Recently, pro-gastrin-releasing peptide (Pro-GRP) became available as a sensitive, specific, and reliable tumor marker for patients with SCLC. The aim of this study is to determine the most useful tumor marker to detect the relapse of SCLC. Furthermore, we analyzed the relationship between tumor markers at relapse and survival from relapse or response to salvage chemotherapy. Medical records were reviewed to obtain serum levels of Pro-GRP, NSE, and CEA before and after the initial chemotherapy, and at relapse. Consecutive 66 patients with SCLC, with an objective response and confirmed relapse treated at the National Cancer Center Hospital East, were analyzed in this study. The percentages of patients whose tumor marker level were elevated before treatment, decreased after the treatment, and increased again at relapse were 67% (95% CI, 55-78) for Pro-GRP, 20% (10-29) for NSE, and 38% (26-50) for CEA. Multivariate analysis indicated that poor performance status before initial treatment and elevated serum levels of lactate dehydrogenase at relapse were poor prognostic factors for patients with recurrent SCLC (P<0.005). None of the serum levels of Pro-GRP, NSE, and CEA at relapse was a significant prognostic factor and associated with an objective response to salvage chemotherapy. The present study demonstrated that serum levels of Pro-GRP reflect the disease course of patients with SCLC most accurately.
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Biomarcadores Tumorais/sangue , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Idoso , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Fosfopiruvato Hidratase/sangue , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Proteínas Recombinantes/sangue , Estudos Retrospectivos , Terapia de Salvação , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
We report a case of unique double primary lung cancers with neuroendocrine features in a 63-year-old male smoker. The mass in the left lower lobe (LLL) was a small cell/large cell carcinoma with spindle cell sarcomatous areas and organoid structure. The mass in the left upper lobe (LUL) was a tubular adenocarcinoma with neuroendocrine features including organoid nests showing occasional rosette formation, nuclear palisading in the periphery of the nests and positive immunoreaction for CD56, chromogranin A and synaptophysin. The difference in histological structures between the two masses led us to diagnose double primary lung cancer. The combination of small cell lung carcinoma and spindle cell carcinoma is very uncommon. The relationship between LLL and LUL tumors remains unclear. Multiple lung cancers with neuroendocrine features have only rarely been reported in the literature. The patient in our case died of widespread cancer 2 years and 4 months after the surgery without adjuvant chemotherapy, a longer postoperative survival time than in cases of ordinary extensive small cell lung cancer. Multiple lung cancers with neuroendocrine features are extremely rare and similar cases have not been reported in the literature. Neuroendocrine differentiation has attracted widespread attention and, therefore, examining neuroendocrine features in lung cancers is important.
Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Tumores Neuroendócrinos/patologia , Adenocarcinoma/química , Antígeno CD56/análise , Carcinoma/química , Carcinoma de Células Grandes/química , Carcinoma de Células Pequenas/química , Cromogranina A , Cromograninas/análise , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/química , Tumores Neuroendócrinos/química , Sinaptofisina/análiseRESUMO
The histogenesis of meningothelial-like nodule or so-called minute pulmonary chemodectoma remains unclear, with various immunohistochemical analyses giving inconsistent results. We performed an immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules. Thirty-one histologically defined meningothelial-like nodules in 14 cases were stained immunohistochemically. One case had multiple lesions with brown pigment granules, which were positively stained with Berlin blue method, indicating the presence of hemosiderin. All meningothelial-like nodules were positive for vimentin and epithelial membrane antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24 lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen. Alveolar macrophages were intensely positive for CD68 and lysozyme in all examined cases. We analyzed the clonality of 11 minute pulmonary meningothelial-like nodule lesions in two female cases based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). The HUMARA was found to be amplified with or without prior digestion by the methylation-sensitive restriction endonuclease HpaII. Six of 11 lesions showed monoclonal expansion. Five lesions in a multiple case showed different patterns of monoclonality. Our findings showed that minute pulmonary meningothelial-like nodules have meningothelial-like and phagocytic characteristics but no muscular phenotype. Furthermore, some minute pulmonary meningothelial-like nodules may show monoclonal expansion, whereas others are polyclonal. Our data indicate that minute pulmonary meningothelial-like nodules are reactive rather than neoplastic.
Assuntos
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Paraganglioma Extrassuprarrenal/genética , Paraganglioma Extrassuprarrenal/patologia , Biomarcadores/análise , Células Clonais , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Macrófagos Alveolares/citologia , Masculino , Paraganglioma Extrassuprarrenal/química , Reação em Cadeia da PolimeraseRESUMO
Atypical adenomatous hyperplasia (AAH) of the lung has been postulated as a possible precursor lesion of bronchioloalveolar carcinoma (BAC). The clonality of AAHs from seven female patients was analyzed to determine whether AAH is a monoclonal expansion. All AAHs were identified in lungs surgically resected for BAC. The clonality of the BAC and bronchiolar metaplasia in each case was also analyzed. Approximately 500 cells in each lesion were precisely microdissected from methanol-fixed sections. Adjacent normal lung tissue was collected as a normal control. DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). HUMARA was found to be amplified with or without previous digestion by the methylation-sensitive restriction endonuclease Hpa II. Five cases were informative. All 10 AAHs and 7 BACs obtained from the informative cases showed monoclonality, whereas the control cells showed polyclonality. Three different AAH lesions in a single case showed both possible patterns of monoclonality. BAC and contiguous AAH showed identical monoclonality in two cases. Two lesions of bronchiolar metaplasia, which was considered reactive, were polyclonal. Our results demonstrated the monoclonal nature of AAH, and this finding suggests that AAH is a precursor of BAC or a preneoplastic condition.
Assuntos
Adenoma/patologia , Pulmão/patologia , Adenocarcinoma Bronquioloalveolar/patologia , Idoso , Células Clonais/patologia , Feminino , Marcadores Genéticos , Humanos , Hiperplasia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Lesões Pré-Cancerosas/patologia , Receptores Androgênicos/genéticaRESUMO
Adenosquamous carcinoma of the lung is a subset of pulmonary carcinomas, and comprises less than 4% of lung carcinomas. Its histogenesis remains unclear. The clonality of adenosquamous carcinoma from four female patients was analyzed to determine whether the clonality between the squamous cell and adenocarcinomatous components coincides. Each lesion was precisely microdissected from methanol-fixed sections. Adjacent normal lung tissue was collected as a normal control. DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). HUMARA was found to be amplified with or without previous digestion by the methylation-sensitive restriction endonuclease HpaII. All four cases were informative. Squamous cell and adenocarcinomatous components showed identical monoclonal patterns in all four patients. In one case, only the squamous cell carcinomatous component showed loss of heterozygosity of the HUMARA locus. The results suggest that the squamous cell and adenocarcinomatous components originate from the same cell.
Assuntos
Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores Androgênicos/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Células Clonais , DNA de Neoplasias/análise , Feminino , Ligação Genética , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Cromossomo XRESUMO
BACKGROUND: Docetaxel, cisplatin and mitomycin C are some of the active drugs used in the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose of the three drugs in combination for such patients. METHODS: Chemotherapy-native patients with metastatic NSCLC were enrolled in this study. The doses of docetaxel and cisplatin were fixed at 60 and 80 mg/m2, respectively. It was planned to increase the dose of mitomycin C from 4 to 6 and 8 mg/m2. All drugs were administered on day 1 and repeated every 3-4 weeks. RESULTS: All six patients received 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin, three of them with 4 mg/m2 of mitomycin C (level 1) and the other three with 6 mg/m2 of mitomycin C (level 2). Two of the three level 2 patients experienced dose-limiting toxicities (DLTs) in first cycle: febrile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was concluded to be 60 mg/m2 for docetaxel, 80 mg/m2 for cisplatin and 6 mg/m2 for mitomycin C. Evaluation of the data from all of the cycles, however, showed that four of the six patients experienced DLTs. CONCLUSIONS: The addition of mitomycin C to docetaxel and cisplatin resulted in relatively high toxicities. It was impossible to use a high enough dose of mitomycin C to improve the survival of NSCLC patients. We therefore concluded that further evaluation of this combination is unwarranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hiponatremia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivadosRESUMO
Sclerosing hemangioma of the lung remains poorly understood, and it is still unclear whether this lesion is neoplastic or not. It consists of two major cell types, pale cells and cuboidal cells. We analyzed the clonality of each cell types from six female cases of surgically resected sclerosing hemangioma. The pale cells and cuboidal cells were separated by microdissection from methanol-fixed sections, and DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor (HUMARA) gene or the phosphoglycerate kinase (PGK) gene. The HUMARA and PGK genes were found to be amplified with or without digestion by the methylation-sensitive restrictive endonuclease HpaII. Five of six cases were informative. Pale cells and cuboidal cells showed the same monoclonality in all of the informative cases, whereas the control cells showed a polyclonal pattern. Our results demonstrated that sclerosing hemangioma is caused by monoclonal expansion of cells, confirming that it is a neoplasia. Moreover, the present data indicate that both pale cells and cuboidal cells are derived from the same cell.
Assuntos
Células Clonais/patologia , Histiocitoma Fibroso Benigno/patologia , Neoplasias Pulmonares/patologia , Adolescente , Adulto , DNA de Neoplasias/análise , Feminino , Histiocitoma Fibroso Benigno/genética , Humanos , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Fosfoglicerato Quinase/genética , Reação em Cadeia da Polimerase , Receptores Androgênicos/genéticaRESUMO
Although percutaneous ethanol injection is widely used to treat hepatic tumors, this technique has not been applied to lung tumors. We performed a preliminary experiment with percutaneous ethanol injection into the rabbit lung, and evaluated the local and systemic effects of absolute ethanol injection on pulmonary structures in order to assess the feasibility and safety of this technique as a local treatment for human lung tumors. Percutaneous injection of absolute ethanol into the rabbit lung was performed under CT guidance. The volume of ethanol injected ranged from 0.6 to 1.0 ml (approximately 0.2-0.5 ml/kg). Follow-up CT scans were performed 1, 2, 7 and 30 days after the injection. The animals were killed at intervals (range: 3 h-30 days), and the lung was examined histologically. The ethanol was well tolerated and did not induce significant systemic side-effects. All doses induced necrosis in the injected lung, but none was lethal. Although ethanol spilling into the thoracic cavity induced effusion and pleuritis, these reactions were manageable. Alcohol injection produced an area of necrosis surrounded by pulmonary edema associated with polymorphonuclear cells invasion within 24 h; moreover, granulation change, epithelial regeneration, and alveolar septal fibrosis had appeared by one week. The necrosis was sometimes multifocal, probably due to transbronchial spread of the injected ethanol. In conclusion, the feasibility and safety of absolute ethanol injection were confirmed. Neither severe systemic side effects nor lethal extensive necrosis were observed with injected ethanol; however, an unexpected side effect, multifocal necrosis, was seen. The latter reaction suggests that careful observation and care would be essential after alcohol injection into the lung.