RESUMO
We aimed to ascertain the implementation of body composition assessment, by means of fat-free mass index (FFMI), fat mass index (FMI) and presence of sarcopenic obesity, in colorectal cancer population, on the basis of hospital length of stay (LOS) determination and to benchmark their discriminatory performance with other nutrition status algorithms, such as body mass index (BMI) and Malnutrition Universal Screening Tool (MUST). Ninety adult patients with operable colorectal cancer were enrolled. Study parameters included demographic and anthropometric data registration, BMI and MUST calculation and body composition parameters measurement within 24-h post-admission. Hospital LOS constituted the outcome of interest, using 7 days as cut-off point. Fifty-one patients (56.7%) were hospitalised for ≤7 days. The presence of sarcopenic obesity affected adversely hospital LOS (OR, 9.236; 95% CI, 3.278-26.173, P = 0.000). Low FFMI (OR, 7.457; 95% CI, 2.868-19.390, P = 0.000), malnutrition according to MUST (OR, 2.632; 95% CI, 1.280-5.413, P = 0.009) and high FMI (2.133; 95% CI, 1.111-4.094, P = 0.023) were the most powerful discriminators of accelerated hospitalisation. Loss of lean body tissue, gain of adipose tissue and sarcopenic obesity confer noteworthy prognostic value being superior or equivalent to MUST in terms of hospital LOS determination in colorectal cancer resection setting. BMI presents inferior discrimination performance in this field.
Assuntos
Composição Corporal , Neoplasias Colorretais/cirurgia , Tempo de Internação/estatística & dados numéricos , Desnutrição/epidemiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Tecido Adiposo , Idoso , Antropometria , Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Comorbidade , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Medição de RiscoRESUMO
OBJECTIVES: Relaxin (RLX) is involved in extracellular matrix and collagen remodelling. The therapeutic role of the circulating isoform RLX-2 as an anti-fibrotic factor in systemic sclerosis (SSc) has been investigated. Several RLX family peptide receptors (RXFPs) are recognized in humans: RLX-2 is a ligand for RXFP1/LGR7 and RXFP2/LGR8. The aim of this study was to define the pattern of expression of LGR7 in different types of human skin cells and to compare normal skin with lesional and unaffected skin from patients with limited SSc (lSSc). METHOD: We analysed RXFP1 immunolocalization on skin biopsies and cultured fibroblasts from lSSc patients and control subjects. Western blot analysis was carried out on fibroblast lysates. RESULTS: RXFP1 showed cytoplasmic localization on skin cells from control subjects and non-lesional skin from lSSc patients: keratinocytes, gland epithelial cells, endothelium, smooth muscle cells, and fibroblasts. Immunogold electron microscopy confirmed a diffuse epithelial cytoplasmic localization of RXFP1. A substantially lower RXFP1 expression was observed in scleroderma skin, with a lack of staining in most cells. Occasional weak reactivity was observed in cultured scleroderma fibroblasts, while control fibroblasts showed a diffuse cytoplasmic immunoreactivity of RXFP1, confirmed by Western blot analysis. CONCLUSIONS: The decreased cellular expression of RLX-2 receptor RXFP1 in scleroderma skin might represent a pro-fibrotic factor and contribute to the substantial inefficacy of RLX treatment in SSc, as reported in the literature. The pathophysiology of the decrease in RXFP1 may be linked to high RLX-2 serum levels previously detected in SSc, but it has yet to be elucidated.
Assuntos
Fibroblastos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/metabolismo , Escleroderma Sistêmico/metabolismo , Pele/metabolismo , Idoso , Células Cultivadas , Feminino , Fibroblastos/patologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Pele/patologiaRESUMO
Trastuzumab (T) is effective in metastatic breast cancer (MBC) with HER2 overexpression and/or amplification, but resistance to T develops in a significant number of HER2-positive patients. Understanding the mechanisms of resistance is critical to the care of these patients. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 256 patients with T-treated MBC. Clinical information was collected retrospectively from the patients' medical records. Central review of HER2 status by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC) revealed that of the 227 eligible patients only 139 (61%) were truly HER2-positive. PTEN, ER, PgR, and Ki67 were evaluated by IHC, while PTEN status was evaluated by FISH as well. PIK3CA mutations were identified with single nucleotide polymorphism (SNP) genotyping. Median time to progression (TTP) was 14.4 months for the HER2-positive and 10.3 for the HER2-negative patients (log-rank, P = 0.22). Survival from the initiation of T (survivalT) was 50.4 months for the HER2-positive and 35.3 for the HER2-negative subgroups (P = 0.006). Higher risk of progression was associated with HER2-positive status and the presence of PIK3CA mutations (P = 0.014). PTEN loss, as determined by IHC, was associated with lower survivalT in the whole population (P = 0.029) and in the HER2-positive population (P = 0.017). PIK3CA mutations and/or PTEN loss status were evaluated together as a single parameter, to estimate the impact of activation of the PI3K/AKT molecular pathway, and it was significantly associated with both decreased TTP (P = 0.003 in the total population, P = 0.004 in HER2-positive patients) and survival (survivalT, P = 0.011 in total, P = 0.006 in HER2-positive). In this trastuzumab-treated breast cancer population, PIK3CA activating mutations were associated with shorter TTP and PTEN loss with decreased survival. The activation of the PI3K/AKT pathway from either defect was associated with both TTP and survival, indicating the adverse effect of this pathway's status on trastuzumab efficacy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Mutação/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Análise Serial de Tecidos , Trastuzumab , Resultado do TratamentoRESUMO
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disorder characterized by a progressive fibrosis which involves skin and internal organs, caused by microvascular damage. The earliest clinical sign of the disease is Raynauds Phenomenon, a vasospastic response to cold or stress stimuli, followed by the skin and organ involvement over time. This kind of vascular manifestation originates from the microvascular structural alteration, characterized by an abnormal myocyte cell proliferation, intima cell proliferation and adventitia fibrosis. The microvascular damage seems to be the consequence of the autoimmune attack to the endothelium, followed by inflammatory cascade and massive deposition of collagen. From the beginning of the disorder, serum Endothelin-1 (ET- 1) is found in very high concentration: this protein, today, is considered one of the most important mediators of scleroderma vascular alterations. Furthermore, many recent studies have shown that ET-1 is involved in the inflammatory and fibrotic processes, increasing the concentration of pro-fibrotic and pro-inflammatory cytokines. The aim of this review is to clarify the ET-1 role in SSc, in particular the relationship between ET-1 and cytokine expression, adding another element to the understanding of scleroderma disease.
Assuntos
Citocinas/biossíntese , Endotelina-1/fisiologia , Escleroderma Sistêmico/imunologia , Actinas/análise , Humanos , Escleroderma Sistêmico/tratamento farmacológicoRESUMO
Haptoglobin (Hpt) is an acute phase protein characterized by three major phenotypes (Hpt 1-1, Hpt 2-1 and Hpt 2-2). The Hpt 2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, the Hpt 2-2 phenotype induces a shift from Th1 to Th2 response and increases fibrotic processes. On this basis, we performed serum proteomic analysis of patients with Systemic Sclerosis (SSc), a connective tissue disorder associated with Th2-type immune response and characterized by interstitial and perivascular fibrosis due to different factors (including genetic, environmental, immunological and microchimeric factors). Serum of 23 SSc outpatients patients (4 males, 19 females, mean age 54+-5.3 years) diagnosed according to the American Rheumatism Association (ARA) criteria, were considered for the proteomic analysis and compared to serum of 21 control subjects. Serum depleted of HAP was analyzed by 2-DE, and Hpt chain spots were identified by WB. The expression frequency of each Hpt α chain in SSc patients and controls was compared and quantitative analysis of spot expression (percent Vol) was performed. Above all,, our study amplifies the limited data in the literature on proteomic analysis in SSc, also confirming previous data that revealed a significant increase of haptoglobin type 2-2 and a concomitant decrease of the 1-1 phenotype in SSc patients. Moreover, our results demonstrate that c spots are more prevalent in SSc patients than in controls (91.3% vs 55.5%, p<0.05), while the expression frequency of a and b spots does not change. In patients Hpt 2-1 or Hpt 1-1 e spot is less abundant. According to our results, the c and e spots can be considered markers for SSc and thus be of use for the early diagnosis of connective tissue disorders and in establishing appropriate treatment.
Assuntos
Haptoglobinas/biossíntese , Haptoglobinas/genética , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/genética , Biomarcadores , Western Blotting , Eletroforese em Gel de Poliacrilamida , Feminino , Regulação da Expressão Gênica/fisiologia , Frequência do Gene , Humanos , Imunoglobulina G/biossíntese , Isomerismo , Masculino , Pessoa de Meia-Idade , Albumina Sérica/metabolismoRESUMO
Raynaud?s phenomenon (RP) and cutaneous fibrosis are the distinctive manifestations of scleroderma, in which Endothelin-1 plays a fundamental pathogenetic role. Bosentan, an Endothelin-1 receptor antagonist used for the treatment of pulmonary arterial hypertension, retards the beginning of new sclerodermic digital ulcers (DU). This open-label, observational, retrospective study verified the effect of Bosentan on RP and skin fibrosis in sclerodermic outpatients affected by pulmonary arterial hypertension without DU. Fourteen subjects (13 women, 1 man; mean age 60 ± 7.5 years; ten with limited and four with diffuse scleroderma) were observed at baseline (T0) and after four (T1), twelve (T2), twenty-four (T3) and forty-eight (T4) weeks during treatment with Bosentan. They were evaluated for daily quantity and duration of RP attacks and skin thickness (using modified Rodnan total skin score, MRSS). Videocapillaroscopic evaluation was performed at T0 and T4. Bosentan decreased significantly the number and duration of RP attacks, beginning at T2 (p<0.05). Videocapillaroscopy showed significant improvement of microcirculatory patterns at T4 (p<0.05). MRSS decreased throughout the study, reaching the statistical significance at T3 and T4 (p<0.01) in the whole cohort. The present data suggest that Bosentan is effective in stabilizing the microcirculation involvement and in improving skin fibrosis irrespective of scleroderma patterns.
Assuntos
Antagonistas dos Receptores de Endotelina , Doença de Raynaud/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Pele/patologia , Sulfonamidas/uso terapêutico , Idoso , Bosentana , Hipertensão Pulmonar Primária Familiar , Feminino , Fibrose , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Effective anthracycline-free combinations need to be evaluated in metastatic breast cancer (MBC), due to the increased number of patients treated with anthracycline-based adjuvant chemotherapy. PATIENTS AND METHODS: Patients with MBC were randomized to paclitaxel and carboplatin (PCb) every 3 weeks or docetaxel and gemcitabine (GDoc) every 3 weeks or weekly paclitaxel (Pw). Trastuzumab was given to patients with HER-2 over-expressing tumors. The primary endpoint of the study was survival. Quality of life (QoL) and cost were assessed. RESULTS: Totally, 416 eligible patients entered the study. Median survival times were 29.9 months for PCb, 26.9 for GDoc and 41.0 for Pw (P = 0.037). According to multivariate analysis, adjuvant chemotherapy, >1 metastatic sites, lack of maintenance hormonal therapy, and worse performance status (PS) were significant adverse prognostic factors for survival, while Pw when compared to GDoc improved survival (P = 0.03), as well as when compared to PCb in the subgroup of patients with PS = 1 (P = 0.01, treatment by PS interaction P = 0.03). No significant differences in terms of time to progression were found. Severe myelotoxicity and mucositis were more frequent with GDoc, while severe neuropathy with PCb and Pw. QoL changes did not differ significantly between treatment groups, while cost analysis favored Pw. CONCLUSIONS: Pw appears to be the most preferable choice among the 3 anthracycline-free taxanes-based regimens tested in the present study.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Taxoides/administração & dosagem , Trastuzumab , GencitabinaRESUMO
BACKGROUND: Erythropoietin corrects and prevents anemia and decreases the need for red blood cell (RBC) transfusions; its impact on quality of life (QOL) of cancer patients receiving chemotherapy is not clear. PATIENTS AND METHODS: 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were randomized to receive or not 10,000 IU epoetin-alpha thrice weekly. QOL was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale and various subscales at baseline, at two months and at the end of the study. RESULTS: Changes in the average QOL scores were similar in the two groups. The improvement in Hb levels was significantly higher for the epoetin-alpha group, with a decrease in transfusion requirements compared to the control group. CONCLUSION: Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales, despite improving Hb levels and reducing transfusion requirements.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eritropoetina/uso terapêutico , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Anemia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transfusão de Sangue , Epoetina alfa , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Qualidade de Vida , Proteínas Recombinantes , Resultado do Tratamento , Adulto JovemRESUMO
The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT-PCR). The overall concordance between kRT-PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT-PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.
Assuntos
Neoplasias da Mama/genética , Receptores ErbB/genética , RNA Mensageiro/análise , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Adulto , Idade de Início , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-4 , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Quimioterapia Adjuvante , Mastectomia , Adulto , Idoso , Androstadienos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma/radioterapia , Carcinoma/secundário , Carcinoma/cirurgia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Estrogênios , Feminino , Fluoruracila/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Humanos , Metástase Linfática , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/cirurgia , Segunda Neoplasia Primária/epidemiologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tamoxifeno/administração & dosagemRESUMO
BACKGROUND: Cancer of unknown primary (CUP) lacks established therapy although it affects 3% of cancer patients. We evaluated the irinotecan-oxaliplatin combination (IROX regimen) in previously untreated patients with non-favorable subsets of unknown primary carcinomas. METHODS: This was a multicenter phase-II trial. Protocol treatment consisted of oxaliplatin 80 mg/m(2) followed by irinotecan 160 mg/m(2) administered every 3 weeks. The primary end points were response rate and toxicity, and secondary end points were time to progression and survival. RESULTS: Forty-seven patients with liver, bone or multiple visceral metastases entered into the trial and received a median 6 chemotherapy cycles (1-11). The regimen was very well tolerated with one febrile neutropenia case and six cases with diarrhea grade 3 (16%). In intent-to-treat analysis the tumor response rate was 13% (95% CI = 4.8-25.7%) and 12 patients (27%, 95%CI 13.9-40.4%) had at least 4 months' duration of disease stabilization. The median time to progression was 2.7 months and the median survival was 9.5 months, with 40% of patients alive at 1 year. CONCLUSIONS: The IROX regimen demonstrated similar efficacy and a favorable toxicity profile compared to other more toxic chemotherapy combinations in patients with poor-prognosis CUP.
Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/mortalidade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , OxaliplatinaRESUMO
Somatic tyrosine kinase (TK) domain mutations of the epidermal growth factor receptor (EGFR) gene are associated with sensitivity of non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKI's), however their incidence in distinct populations is not clarified. We sequenced exons 18-21 of the EGFR TK domain from 60 Greek and Czech patients, enrolled in an adjuvant chemotherapy trial following total resection for stages I-IIIa disease. Somatic mutations were found in 9/60 patients (15.0%), several being novel. EGFR mutations were more common in Stage I tumors (p = 0.023), they were also more common in women and never smokers; however, no other significant association of clinicopathological features with mutations was found. Median TTP and OS of patients with and without mutations were 13.2 and 40 months compared to 22.9 and 43.2 months, respectively. These differences were not statistically significant. K-ras (5/60, 8%) and EGFR mutations were found to be mutually exclusive. We identified a wide spectrum of somatic EGFR TK mutations reporting a relatively high incidence (15%) in NSCLC patients of Greek and Czech origin. As ethnicity seems to be a factor for the origin of these mutations, further studies in distinct populations are warranted.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação de Sentido Incorreto , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Éxons , Feminino , Genes ras/genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated. MATERIALS AND METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients aged < and > than 45 years old were compared and evaluated for prognostic significance regarding outcome. RESULTS: The data for NSCLC patients (1906), of whom 115 were aged <45, were retrieved. In comparative analysis, the young patients were more frequently asymptomatic at diagnosis, while older patients presented significantly higher rates of thoracic pain, cough and fatigue (p<0.01). The young patients were more commonly diagnosed with adenocarcinoma and less frequently with squamous cancer than patients aged over 45. Although the stage distribution was distinct, with older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the rates of early lung cancer (stages I-IIIa) were similar. The overall survival (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277). Among patients who underwent first-line palliative chemotherapy, young individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months (p=0.0049). Univariate and multivariate regression analyses established the prognostic usefulness of the performance status, disease stage and disease-free interval for the risk of death, both in the total number of patients (1906) and in young patients (115). CONCLUSION: This large retrospective series failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity with differing biological behavior, since the same clinicopathological prognostic factors were valid in both age groups. Molecular phenotypic studies are needed to shed light on this controversial subject.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Fatores Etários , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To compare the efficacy of two different schedules of epirubicin and paclitaxel, as first-line chemotherapy, in patients with advanced breast cancer (ABC). PATIENTS AND METHODS: From October 1997 until May 1999, 183 eligible patients with ABC entered the study. Chemotherapy in group A (93 patients) consisted of four cycles of epirubicin at a dose of 110 mg/m(2) followed by four cycles of paclitaxel at a dose of 225 mg/m(2) in a 3-hour infusion. All cycles were repeated every 2 weeks with granulocyte colony-stimulating factor support. The therapeutic regimen in group B (90 patients) consisted of epirubicin (80 mg/m(2)) immediately followed by paclitaxel (175 mg/m(2) in a 3-hour infusion) every 3 weeks for six cycles. RESULTS: In total, 79 patients (85%) in group A and 72 patients (80%) in group B completed treatment. The median relative dose-intensity of epirubicin was 0.96 in both groups, and that of paclitaxel was 0.96 and 0.97 in groups A and B, respectively. The complete response rate was higher in group A (21.5% v 9% P =.02). Nevertheless, there was no significant difference in the overall response rate between the two groups (55% v 42%, P =.10). Severe neutropenia was more frequently observed with concurrent treatment. After a median follow-up of 16.5 months, median time to progression was 10 months in group A and 8.5 months in group B (P =.27), and median survival was 21.5 and 20 months, respectively (P =.17). CONCLUSION: The present study failed to demonstrate a significant difference in overall response rate between dose-dense sequential administration of epirubicin and paclitaxel compared with the combination of the two drugs given on the same day, even though the sequential treatment resulted in a significantly higher complete response rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS: Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. RESULT: Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. CONCLUSION: MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Progressão da Doença , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Prognóstico , Taxoides/administração & dosagem , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Neoplasias Urológicas/patologia , Vimblastina/administração & dosagemRESUMO
A phase II study was conducted to evaluate the activity of paclitaxel and carboplatin in advanced head and neck cancer. Twenty-four patients with measurable locoregional squamous cell carcinoma and metastatic disease were entered. All had been heavily pretreated with radiotherapy, surgery and chemotherapy and were at second recurrence or disease progression when they entered the trial. Patients received Paclitaxel 200 mg/m2 with carboplatin 7 AUC once every 3 weeks with premedication with dexamethasone and diphenyldramine and ranitidine. Twenty-three patients were evaluable for response. Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months. Toxicity was tolerable. Four patients showed Grade III (WHO) and 6 Grade II neutropenia. Nineteen (79%) of patients who received more than two courses of chemotherapy presented neurotoxicity. The combination of paclitaxel and carboplatin was effective in heavily pretreated patients with squamous cell carcinoma of the head and neck.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do TratamentoRESUMO
The purpose was to evaluate the efficacy and safety profile of docetaxel as first-line chemotherapy for patients with locally advanced or metastatic biliary tract carcinoma. 25 chemotherapy-naïve patients with unresectable or metastatic biliary tract carcinoma were entered into this phase II trial. Docetaxel was given at the dose of 100 mg/m2 as a 1-h infusion on day 1, after appropriate premedication with dexamethasone; treatment was repeated every 21 days. Patients were assessed for response every three chemotherapy cycles. 24 patients were evaluable for response and 25 for toxicity. A total of 98 cycles were administered with a median of three cycles/patient. Two complete (CR=8%) and three partial (PR=12%) responses were observed (overall response rate: 20%; 95% confidence interval (C.I.) 4-36%); in addition, 6 (24%) patients had stable disease and 14 (58%) progressive disease. With a median follow-up of 8 months, the median duration of response was 4 months, the median time to tumour progression (TTP) was 6 months and the overall median survival was 8 months. The 1-year survival rate was 26%. Grade 3 and 4 granulocytopenia occurred in 36 and 20% of the patients, respectively, and febrile neutropenia was observed in 16% of them; there were no treatment-related deaths. Grade 2-3 fatigue was reported in 24% of patients. These results indicate that docetaxel is an active drug against adenocarcinomas of the biliary tract.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Paclitaxel/uso terapêutico , Taxoides , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivados , Cooperação do Paciente , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Ninety previously untreated patients with advanced epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages IIC, III, and IV) were randomized, after initial cytoreductive surgery, to receive paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 as a 3-hour infusion with either carboplatin at an area under the concentration-time curve of 7 (group A) or carboplatin at an area under the concentration-time curve of 7 on courses 1, 3, and 5, alternating with cisplatin 75 mg/m2 on courses 2, 4, and 6 (group B). Treatment was given every 3 weeks, up to a total of six courses. Sixty-one patients (33 and 28 patients in groups A and B, respectively) had residual disease after the initial cytoreductive surgery. Patients with measurable or evaluable disease had a high overall response (82% v 57%). A 52% and 39% complete response rate for groups A and B, respectively, with no statistically significant difference between the groups was also observed. With a median follow-up of 12 months (range, 0.33 to 24 months), 29 patients have progressed (18 and 11 in groups A and B, respectively), and 13 have died (seven and six, respectively). Median time to progression was 20.36 months (range, 0.20 to 23.54 months) for group A, whereas this has not yet been reached for group B. Median survival has not yet been reached, but there is no significant difference between the two groups (P = .6972). Treatment was generally well tolerated. Grade 3 and 4 neutropenia was 20% and 32% for groups A and B, respectively, while grade 3 and 4 thrombocytopenia was 4% and 7%, respectively, with no significant difference between the two groups. In conclusion, both combinations seem very active for the treatment of advanced epithelial ovarian cancer and are associated with acceptable toxicity.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Carboplatina/efeitos adversos , Causas de Morte , Cisplatino/efeitos adversos , Terapia Combinada , Progressão da Doença , Esquema de Medicação , Feminino , Seguimentos , Grécia , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/efeitos adversos , Indução de Remissão , Taxa de Sobrevida , Trombocitopenia/induzido quimicamenteRESUMO
Six patients with metastatic breast cancer and malignant pleural effusions and 13 patients with known or suspected ovarian cancer, underwent immunoscintigraphy after intracavitary (intrapleural or intraperitoneal) administration of iodine-131-(131I) or indium-111-(111In) labeled tumor associated monoclonal antibodies HMFG2 and H17E2. This method proved to be sensitive and specific with a true-positive result in 13 out of 14 patients with tumor and a true-negative result in five out of five patients without tumor. At any one time, 65%-80% of the whole-body radioactivity was closely associated with the cavity into which the radiolabeled antibody was administered while the radioactivity in the blood was always low, (approximately 4 X 10(-3) of administered dose/ml of blood). Concentrations of radiolabeled antibody (per gram of tumor tissue) ranged from 0.02%-0.1% of the injected dose in intracavitary tumors, but only 0.002% in a retroperitoneal metastasis. The specificity of this approach was documented in four control patients with benign ovarian cysts and in two patients who were imaged using both specific and nonspecific radiolabeled antibody. We conclude that the intracavitary administration of 131I- or 111In-labeled HMFG2 and H17E2 is a favorable route of administration and offers significant advantages over previously reported intravenous administration for the localization of breast or ovarian metastases confined to the pleural or peritoneal cavities.