RESUMO
BRIIL-2 is a clinical study for evaluation of efficacy and toxicity of third line treatment of pulmonary metastasis from renal cancer and melanoma with flexible bronchoscopic istillation of IL-2. Moreover, we evaluate local (BALT) and peripheral lymphocytic activation during this IL-2 administration. Up today we enrolled two patients with pulmonary metastasis from renal cancer already treated with two lines of molecular therapy, chemotherapy or systemic immunotherapy. Regarding to immunologic stimulation, lymphocytic fraction decreased from 21 to 2% in the first and from 10.5 to 6% in the second patient, indicating lymphocytic enrollment for activation, while TCD4/CD8 ratio is stable. In both patients we also observed a significant increase of HLA-DR in T lymphocytes (CD3) either in BAL or in peripheral blood. No significant major toxicities were observed after broncho-istillation, even if the dose was progressively increased. Thus IL-2 broncho-istillation could represent a valid administration modality to obtain an effective immunologic stimulation either local or systemic.
Assuntos
Broncoscopia , Carcinoma de Células Renais/secundário , Interleucina-2/uso terapêutico , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Linfócitos T/efeitos dos fármacos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Líquido da Lavagem Broncoalveolar/citologia , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/terapia , Terapia Combinada , Feminino , Tecnologia de Fibra Óptica , Antígenos HLA-DR/biossíntese , Antígenos HLA-DR/genética , Humanos , Instilação de Medicamentos , Interleucina-2/administração & dosagem , Neoplasias Renais/sangue , Neoplasias Renais/imunologia , Neoplasias Renais/cirurgia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Ativação Linfocitária/efeitos dos fármacos , Contagem de Linfócitos , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Nefrectomia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
OBJECTIVE: The aim of this study was to assess the diagnostic role of fiberoptic bronchoscopy in primitive lung cancers in relation to the sensibility, the specificity and the cost of the examination. MATERIALS AND METHODS: We analysed the diagnostic flow-charts of 473 patients with suspected primitive lung cancer consecutively examined during a period of 4 years (2003-2006). The results were analysed comparing patients observed in the period 2003-2004 with those observed during 2005-2006. The number and type of samples collected and the protocols utilized were considered. RESULTS: In overall patients the reliability of the fiberoptic bronchoscopy was 61.7%, with a significant increase from 47.5% in 2003-2004 to 74.4% in 2005-2006. An important role in improving the diagnostic relevance of the exam was assumed by the more frequent adoption of biopsies and trans-bronchial needle aspiration on parenchyma and mediastinal lymph nodes. CONCLUSIONS: The fiberoptic-bronchoscopy associated to advanced tissue sampling techniques represents the gold standard for the diagnosis of lung cancer, due to high sensitivity and specificity and moderate cost.
Assuntos
Broncoscopia/métodos , Neoplasias Pulmonares/patologia , Tecnologia de Fibra Óptica , Humanos , Sensibilidade e EspecificidadeRESUMO
The exposure to DNA reactive carcinogens is known to elicit a specific humoral immunological response, with the production of antibodies towards the carcinogen adducts. In analogy to chemical carcinogens, any chemotherapic, like Adriamycin, undergoes the same adduct formation, and for this reason could elicit specific antibodies. In this case we can suppose that an eventual immunological response could influence the efficacy of chemotherapy. The aim of this study was to verify if adriamycin adducted to DNA or transport proteins can elicit an immunological response of specific anti-adriamycin (ADM) antibodies in sera of 43 cancer patients treated with the drug. No specific antibodies were detected in these individuals. The lack of anti-adriamycin antibodies suggests that the therapeutic exposure to the drug does not elicit a specific immunological response.
Assuntos
Antineoplásicos/imunologia , Adutos de DNA/imunologia , Doxorrubicina/imunologia , Epirubicina/imunologia , Imunoglobulina G/sangue , Neoplasias/sangue , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Epirubicina/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: This study evaluated the toxicity of high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeks and compared the dose-intensity achieved with this schedule with that obtained in a previous study we conducted in which the same regimen was given every 3 weeks without G-SCF (EC 21). The secondary objective was to explore the activity of this regimen. PATIENTS AND METHODS: Between December 1991 and March 1994, 41 patients (pts), 19 with locally advanced breast cancer (LABC) and 22 with metastatic breast cancer (MBC), were given high-dose epirubicin (Hd-Epi) (120 mg/m2) and cyclophosphamide (CTX) (600 mg/m2) on day 1 every 14 days (EC 14) plus granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/d s.c. on days 2-12). A total of 8 cycles in LABC pts (4 pre- and post-surgery), and 6-8 cycles in MCB pts were administered. The results were compared with those obtained in the previous study. RESULTS: The incidence of WHO grade 3-4 neutropenia was significantly reduced in the EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214 and 250 evaluable cycles, respectively, p<0.0001), as well as the incidence of neutropenic fever (7% vs. 3%, p=0.05). Grade 3-4 anemia (36.6% vs. 8% pts, p=0.001) and grade 3-4 thrombocytopenia (17.1% vs. 0 pts, p=0.002), were significantly more frequent in EC 14 + G-CSF. No significant differences in the other side effects were found. A total of 17 of 207 of the cycles (8.2%) were delayed in the EC 14 + G-CSF vs. 58/271 (21.4%) in the EC 21 (p<0.0001). The main reasons for these treatment delays were neutropenia (1% vs. 15%), anemia (3% vs. 0) and thrombocytopenia (1% vs. 0). As a result of treatment acceleration and differences in dose delays, the patients on EC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m2/wk vs. 36.8 mg/m2/wk; CTX 292.52 mg/m2/wk vs. 182.9 mg/m2/wk). A complete response at surgery was obtained in 9/19 (47.4%) LABC pts. An objective CR was obtained in 11/22 MBC pts (50%) and a partial response in 8/22 (36.4%), yielding an overall response rate of 86.4%. CONCLUSIONS: Hd-Epi + CTX is very active against both LABC and MBC. The administration of G-CSF allows dose intensification of both drugs (a 59.5% increase of the actual dose intensity) with acceptable clinical tolerance (a lower incidence of neutropenia but a higher incidence of anemia and thrombocytopenia). Only a specifically designed phase III trial will lead to definitive conclusions regarding the greater antitumor activity of accelerated CSF-including regimens as compared to standard chemotherapy for advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Filgrastim , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Proteínas Recombinantes/uso terapêutico , Indução de RemissãoRESUMO
BACKGROUND: Vinorelbine as single-agent has achieved an overall response rate of > 20% as second-line treatment and 40%-50% as first-line treatment. The aim of this study was to evaluate the activity and toxicity of the combination of vinorelbine and thiotepa as second-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-three patients (31: anthracycline-based chemotherapy, 16: high-dose epirubicin) were given vinorelbine 30 mg/m2 and thiotepa 12 mg/m2 d 1 and 8 every 21 days. RESULTS: Among the 32 evaluable patients two complete responses and seven partial responses were observed, for an overall response rate of 28% (C.I. 12-44). The median duration of response was 9 months and the median time to progression 6 months. Significant toxicity was primarily leukopenia (72%); anemia was also frequent (48%) as well as local phlebitis (39%). CONCLUSION: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Resistência a Medicamentos , Feminino , Humanos , Tábuas de Vida , Menopausa , Pessoa de Meia-Idade , Metástase Neoplásica , Flebite/induzido quimicamente , Indução de Remissão , Terapia de Salvação , Análise de Sobrevida , Tiotepa/administração & dosagem , Tiotepa/efeitos adversos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , VinorelbinaRESUMO
Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high-dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Resultado do TratamentoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Ácido Fólico/administração & dosagem , Ácido Fólico/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
One hundred sixteen patients with unresectable locally advanced non-small cell lung cancer (NSCLC) were accrued in a prospective randomized trial comparing (A), chemotherapy (cisplatin and etoposide [VP-16]) for two courses plus radiation therapy (30 + 20 Gy split course), followed by an additional two courses to (B), the same regimen plus the addition of lonidamine (LND). There were 93 patients evaluable for response (46 in the chemotherapy/radiation arm and 47 in the chemotherapy/radiation/LND arm). One hundred fifteen patients were evaluable for toxicity. The overall response rates, median time to progression, and median survival time were similar in both arms. For the group of patients with squamous cell histology, time to progression was 27 weeks on arm A and 38 weeks on arm B (P = 0.01). Two-year survival in the squamous cell group in arm A was 9%, in arm B, 39%. LND does not give rise to additional toxicity, although myalgia and testicular pain are characteristic side effects.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Indazóis/administração & dosagem , Neoplasias Pulmonares/terapia , Pirazóis/administração & dosagem , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Fatores de TempoRESUMO
Sixty-five cancer patients pretreated with chemo or radiotherapy, with granulocytopenia less than 1000/mm3 and without fever, were entered into this study: 30 of them were submitted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group. 20% of the treated subjects versus 68.6% of the controls presented a subsequent infection (P less than 0.001), the lung representing the most frequent site of the infectious disease in both groups (3/6 and 14/24 respectively). These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile, granulocytopenic cancer patients, especially as far as gram-negative infections are concerned. Because of the high prevalence of lung cancer in the patients of our study, and a related prevalence of lung infections, at the present time, a wider use of this antibiotic in every kind of solid tumor cannot be generalized.
Assuntos
Agranulocitose/complicações , Infecções Bacterianas/prevenção & controle , Neoplasias/complicações , Norfloxacino/uso terapêutico , Infecções Bacterianas/etiologia , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , HumanosRESUMO
Fifty-three cases of metastatic pleural effusion (30 haemorragic and 23 serofibrinous) were treated with 4 mg of Corynebacterium parvum (CP) injected weekly into the pleural cavity after total thoracentesis. Of the 53 effusions, 24 were metastases from lung cancer and 29 from breast cancer. Complete response (CR) was assessed as total resolution of pleural effusion after explorative thoracentesis. The results were as follows: 15 CR after two injections of CP, 30 CR after three, and 5 CR after the fourth administration. Three of 53 cases could not be evaluated because of early death. Of the 30 clearly haemorragic effusions, 25 turned into serofibrinosis after the first intrapleural injection of CP and the other five after the second. These findings indicate that intracavitary CP is the most adequate treatment for the control of neoplastic pleural effusion because it induces a significant clinical improvement with milder side effects with respect to other drugs and/or physical agents commonly used.
Assuntos
Vacinas Bacterianas/administração & dosagem , Derrame Pleural/terapia , Propionibacterium acnes/imunologia , Vacinas Bacterianas/efeitos adversos , Neoplasias da Mama/complicações , Feminino , Humanos , Neoplasias Pulmonares/complicações , Microscopia de Contraste de Fase , Pleura , Derrame Pleural/etiologia , Derrame Pleural/patologiaRESUMO
Sixty granulocytopenic patients (granulocytes less than 1000/mm3) affected with solid tumors, previously submitted to antiblastic therapy and with infections, were treated with three antibiotic combinations: amikacin + ceftazidime, amikacin + piperacillin or amikacin + aztreonam. In 68% of the cases the infections were due to gram-negative and in the remaining 32% to gram-positive microorganisms. The results obtained with the three treatments show a slight but significant statistical difference (p less than 0.05), due to the greater efficacy of the amikacin + ceftazidime combination on gram-positive and amikacin + aztreonam on gram-negative bacteria.
Assuntos
Agranulocitose/complicações , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Neoplasias/complicações , Adulto , Aztreonam/uso terapêutico , Infecções Bacterianas/etiologia , Ceftazidima/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperacilina/uso terapêutico , Distribuição AleatóriaRESUMO
Lonidamine was studied in advanced cancer patients. The drug was given orally by single or repeated administrations. Single doses ranged from 150 to 450 mg. Repeated administrations were performed with progressively increasing doses: 450-900 mg daily. Lonidamine lacked severe toxic effects after both single and prolonged administrations. The most common side effect was myalgia; gastrointestinal discomfort was also reported. 1 patient with lung cancer experienced an episode of arrhythmia which subsided upon discontinuation of treatment and did not reoccurr++ when treatment was reinstated. 1 partial and 2 minor responses were observed in the 6 patients with breast cancer.
Assuntos
Antineoplásicos/administração & dosagem , Indazóis/administração & dosagem , Pirazóis/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Sistema Digestório/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Indazóis/efeitos adversos , Indazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Músculos/efeitos dos fármacos , Neoplasias/tratamento farmacológicoAssuntos
Neoplasias Pulmonares/epidemiologia , Adulto , Fatores Etários , Idoso , Bronquite/complicações , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Ocupações , Fatores Sexuais , Fumar , Traumatismos Torácicos/complicaçõesRESUMO
The authors have performed percutaneous fine needle aspiration (FNA) biopsy in 140 patients with pulmonary lesions of suspected neoplastic nature. In 63% of the cases histologic diagnosis could be made on the bioptic sample. Comparison of these findings with those obtained with conventional exfoliative cytology suggest that the latter technique gives higher percentage of histological characterization, it is free of complications and easier to perform. Thus, FNA appears to be an additional, irreplaceable tool when conventional methods fail to provide clear-cut information regarding the histologic nature of pulmonary lesions.