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1.
Anticancer Res ; 42(12): 5795-5801, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36456130

RESUMO

BACKGROUND/AIM: Male breast cancer (MBC) is a very rare disorder affecting approximately 1 in 833 men. Genetic predisposition is one of the most important risk factors of MBC with BRCA2 being the most commonly mutated gene in males diagnosed with breast cancer. However, a large part of MBC heritability is still unexplained. This study sought to add to the data already available on the genetics of MBC. MATERIALS AND METHODS: Our study initially involved comprehensive analysis of BRCA1 and BRCA2, followed by analysis of 43 genes implicated in cancer predisposition in a series of 100 Greek patients diagnosed with MBC between 1995-2015. RESULTS: Pathogenic variants were identified in 13 patients, with BRCA2 being the most commonly affected gene, followed by BRCA1, RAD50, RAD51B, and MSH3. CONCLUSION: In agreement with previous reports, BRCA2 is the most important genetic factor of MBC predisposition, while the remaining known cancer predisposition genes are each very rarely involved, rendering conclusions as to their cumulative effect difficult to draw.


Assuntos
Neoplasias da Mama Masculina , Humanos , Masculino , Neoplasias da Mama Masculina/genética , Predisposição Genética para Doença , Genótipo , Doenças Raras , Fatores de Risco
2.
Cancers (Basel) ; 13(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925588

RESUMO

CHEK2 germline pathogenic variants predispose to breast cancer and possibly to other malignancies, with their spectrum and frequency being variable among populations. Τhe majority of CHEK2-associated breast tumors are hormone receptor positive; however, relevant clinical outcomes are not well defined. Herein, we illustrate the histopathological characteristics and clinical outcomes of 52 Greek breast cancer patients who are CHEK2 carriers. Genetic analysis was performed by Sanger/massively parallel sequencing, followed by MLPA. Subsequent haplotype analysis investigated possible founder effects. Blood relatives were offered cascade testing. CHEK2 variant spectrum was characterized by variability, while influenced by founder effects. The majority of carriers, i.e., 60.8%, were diagnosed with breast cancer before the age of 45. Notably, 91.5% of breast tumors were hormone receptor positive. Hormone therapy and mastectomy at diagnosis seem to have a positive trend on overall survival, after a median follow-up of 9.5 years. Remarkably, 41.9% of patients underwent risk-reducing surgery, one third of which involved salpingo-oophorectomy. Nearly half of families responded to cascade testing. Our data highlight the need for guideline-adherent choices, based on the evidence that CHEK2 carriers are at moderate risk for breast cancer and no risk for ovarian cancer, while underscore the possible role of chemoprevention with tamoxifen.

3.
Clin Breast Cancer ; 20(2): 152-159, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31980407

RESUMO

INTRODUCTION: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations. PATIENTS AND METHODS: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests. RESULTS: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups. CONCLUSIONS: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.


Assuntos
Neoplasias da Mama/genética , Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Carcinoma Medular/genética , Segunda Neoplasia Primária/genética , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Carcinoma Medular/mortalidade , Carcinoma Medular/patologia , Carcinoma Medular/terapia , Quimioterapia Adjuvante , Análise Mutacional de DNA , Feminino , Seguimentos , Predisposição Genética para Doença , Testes Genéticos/estatística & dados numéricos , Grécia , Heterozigoto , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Head Neck Pathol ; 14(3): 689-700, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31749124

RESUMO

To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm2 were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm2). TIL density and CD8+ counts weakly correlated with each other (Spearman's rho = 0.348). Heterogeneous CD8+ counts/mm2 were demonstrated in 28% of the tumors. In univariate analysis, a significant interaction was observed between CD8 expression and nodal status with respect to outcome; in node-positive patients, those with high CD8+ tumors had 77% lower risk of relapse (interaction p < 0.001) and 74% lower risk for death (interaction p = 0.002) compared to patients with low CD8+ tumors. In multivariate analysis, higher TIL density independently conferred lower risk for relapse in the entire cohort (HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017) and in node-positive patients (HR 0.41; 95% CI 0.23-0.75; p = 0.003) and, similarly, for death (p = 0.025 and p = 0.003, respectively). High CD8+ was not a significant independent prognostic marker in any analysis setting. The assessment of CD8+ infiltrates does not seem to offer additional prognostic information over the morphologically assessed TIL density. It also appears that the favorable prognostic impact of higher TIL density and CD8+ infiltrates mostly concerns node-positive but not node-negative disease. If validated in larger node-positive cohorts, these findings are worth considering for the diagnostic development of immune cell infiltrates in LSCC.


Assuntos
Biomarcadores Tumorais/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Laríngeas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
5.
Breast Cancer Res Treat ; 169(1): 105-113, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29335925

RESUMO

PURPOSE: Male breast cancer (MBC) is a rare cancer entity, with mutations in BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing has already entered clinical practice for female breast cancer, whereas the performance of panel testing in MBC has not been studied extensively. Therefore, the aim of this study was to evaluate the clinical utility of panel testing for MBC, by the largest gene panel used so far, through investigation of patients deriving from a population with known founder effects. METHODS: Genomic DNA from one hundred and two Greek MBC patients, unselected for age and family history, was used to prepare libraries which capture the entire coding regions of 94 cancer genes. RESULTS: Loss-of-function (LoF) mutations were found in 12.7% of the cases, distributed in six genes: BRCA2, ATM, BRCA1, CHEK2, PMS2, and FANCL. BRCA2 mutations were the most frequent, followed by ATM mutations, accounting for 6.9 and 2%, respectively, while mutations in other genes were detected in single cases. Age at diagnosis or family history was not predictive of mutation status. Beyond mutations in established breast cancer predisposing genes, LoF mutations in PMS2 and FANCL among MBC patients are reported here for the first time. CONCLUSIONS: Our findings, using the largest gene panel for MBC patients so far, indicate that BRCA testing should be the primary concern for MBC patients. Until sufficient evidence arises from larger studies, multiple-gene panels may be of limited benefit for MBC and their families, at least for MBC patients of specific descent.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama Masculina/genética , Predisposição Genética para Doença , Idoso , Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/patologia , Quinase do Ponto de Checagem 2/genética , Efeito Fundador , Testes Genéticos , Mutação em Linhagem Germinativa/genética , Humanos , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade , Deleção de Sequência/genética
6.
Br J Cancer ; 117(2): 164-170, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28641315

RESUMO

BACKGROUND: Sequential anthracyclines and taxanes are standard adjuvant chemotherapy for patients with high-risk axillary node-positive breast cancer. We compared a sequential to a concurrent regimen in high-risk node-negative early breast cancer. METHODS: Patients were eligible if they had tumours >2 cm or T1c with two of the following characteristics: no oestrogen receptor (ER) and progesterone receptor (PR) expression, histological grade III, Ki67 >40% and vascular, lymphovascular or perineural invasion. They were randomised to receive four cycles of epirubicin 90 mg m-2 followed by four cycles of docetaxel 75 mg m-2 (sequential regimen) or six cycles of epirubicin 75 mg m-2 plus docetaxel 75 mg m-2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with G-CSF prophylaxis only for the concurrent arm. The primary endpoint was disease-free survival (DFS). RESULTS: Between 2001 and 2013, 658 women received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 years, 43.9% of the patients were premenopausal and of the tumours 44.2% were ⩽2 cm, 52.7% histological grade 3 and 35.3% hormone receptor-negative. After a median follow-up of 70.5 months, there were 29 (8.8%) vs 42 (12.8%) disease relapses (P=0.102) and 11 (3.3%) vs 19 (5.8%) deaths (P=0.135), in the sequential and concurrent arm, respectively. The 5-year DFS rates were 92.6% vs 88.2% for sequential and concurrent arm, respectively (hazard ratio (HR): 1.591; 95% confidence interval (CI): 0.990-2.556; P=0.055). Toxicity included grade 2-4 neutropenia in 54% vs 41% (P=0.001), febrile neutropenia 2.7% vs 6.1% (P=0.06), nausea/vomiting 18.5% vs 12.4% (P=0.03) of patients in the sequential and concurrent arm. There were no toxic deaths. CONCLUSIONS: Sequential compared with the concurrent administration of anthracyclines and taxanes is associated with a non-significant but possibly clinically meaningful improvement in DFS. In the era of molecular selection of patients for adjuvant chemotherapy, this study offers valuable information for the optimal administration of anthracyclines and taxanes in patients with node-negative disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias
7.
Pharmacogenomics ; 13(14): 1595-607, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23148636

RESUMO

AIM: The association between two polymorphisms of ERCC1 and treatment outcomes after platinum-based chemotherapy in patients with advanced urothelial cancer (UC) was examined. MATERIALS & METHODS: Genotyping of 19007C>T and 8092C>A polymorphisms was determined by PCR amplification and RFLP in 113 advanced UC patients, treated with platinum-based chemotherapy. RESULTS: Seventy eight patients (69%) were carriers of the 19007T polymorphic allele: 51 (45%) heterozygotes and 27 (24%) homozygotes. Fifty three (47%) patients were carriers of the 8092A polymorphic allele: the frequencies of C/A and A/A genotypes were 37% and 10%, respectively. The T/T genotype was independently associated with prolonged median cancer-specific survival (not-reached vs 14.8 months; p = 0.026). There was no interaction between T/T or any other genotype with the type of platinum derivative (cisplatin/carboplatin). CONCLUSION: 19007C>T, especially in its homozygotic state, but not 8092C>A polymorphism, could be a useful prognostic marker in advanced UC treated with platinum-based chemotherapy.


Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Estudos de Associação Genética , Platina/administração & dosagem , Neoplasias Urológicas/tratamento farmacológico , Idoso , Biomarcadores Farmacológicos , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único/genética , Resultado do Tratamento , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia
8.
Clin Ther ; 34(10): 2132-42, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23063374

RESUMO

BACKGROUND: In 2008, colorectal cancer was the fourth most common cause of cancer-related death worldwide. Monotherapy with monoclonal antibodies directed against the epidermal growth factor receptor, such as cetuximab and panitumumab, has recently been introduced in the management of metastatic colorectal cancer (mCRC) patients. OBJECTIVE: The aim of this study was to conduct a cost-minimization analysis comparing panitumumab with cetuximab in the treatment of patients with epidermal growth factor receptor-expressing mCRC with nonmutated (wild-type) Kirsten rat sarcoma viral oncogene homolog in Greece. The perspective of analysis was that of payers (Social Security Sickness Fund) and the country's National Health Service (NHS). METHODS: The model was designed to contain probabilistic parameters to account for uncertainty and variation in these parameters. All resources consumed in local hospitals in the management of patients in each case were evaluated. Two analyses were performed: 1 evaluating cost per milligram and another evaluating cost per vial. RESULTS: From a payer perspective, the mean 20-week total cost per patient for panitumumab and cetuximab was: (1) per-milligram analysis: €16,349 and €18,242, respectively; and (2) per-vial analysis: €18,808 and €19,701. From the NHS perspective, the mean total costs per patient were slightly higher; however, the use of panitumumab was associated with a 17.7% and 12.4% cost reduction in per-milligram and per-vial analysis, respectively. The results of probabilistic models confirmed those of the deterministic analyses. CONCLUSION: In the Greek NHS and Social Security Sickness Fund setting, panitumumab monotherapy potentially constitutes a cost-saving option (versus cetuximab monotherapy) in the management of patients with mCRC and no mutation of Kirsten rat sarcoma viral oncogene homolog.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Modelos Econômicos , Anticorpos Monoclonais/economia , Anticorpos Monoclonais Humanizados , Antineoplásicos/economia , Cetuximab , Neoplasias Colorretais/economia , Neoplasias Colorretais/patologia , Redução de Custos , Custos de Medicamentos , Receptores ErbB/antagonistas & inibidores , Grécia , Custos Hospitalares , Humanos , Modelos Estatísticos , Metástase Neoplásica , Panitumumabe , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética
9.
Anticancer Res ; 32(4): 1273-81, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22493359

RESUMO

BACKGROUND: The epithelial to mesenchymal transition (EMT) has been associated with metastatic dissemination and poor outcome in several solid tumour types. Our aim was to study its incidence and its prognostic significance in cancer of unknown primary (CUP). PATIENTS AND METHODS: One hundred tumour samples of CUP were loaded in tissue microarrays and were studied for immunohistochemical (IHC) expression of E-cadherin, N-cadherin, vimentin, the EMT transcription factor (SNAIL) and the stem cell marker octamer-binding transcription marker 4(OCT4). An EMT phenotype was defined as low expression of E-cadherin, expression of N-cadherin with/without vimentin with concomitant expression of SNAIL, as assessed by percentage of tumour cell staining. RESULTS: Among 100 CUP cases, the histological diagnosis was adenocarcinoma in 55, squamous carcinoma in 20 and undifferentiated carcinoma in 15, with a high grade seen in 46. Therapy consisted of palliative chemotherapy, mostly platinum based. The median progression-free survival and overall survival (OS) were 7 and 12 months respectively. Distributional studies resulted in selection of IHC cut-offs for E-cadherin (negative when expressed in <60% of tumour cells), N-cadherin, vimentin (positive when expressed in ≥40% of tumour cells), SNAIL (positive when stained in ≥80% of tumour cells). An EMT phenotype was observed in 8 cases (8.1%) and was strongly associated with poor OS (median OS EMT(-)=13 months vs. median OS EMT(+)=8 months, p=0.023). When we used staining intensity (H-Score), an EMT phenotype was observed in 16 patients and carried borderline adverse prognostic utility for outcome (median OS 9 vs. 14 months, p=0.07). The presence of the EMT phenotype correlated significantly with male gender, high grade and presence of visceral metastases (χ(2) p<0.05), while EMT mediator expression was correlated to high NOTCH 2/3 expression. Other factors, prognostic for poor survival, were male gender, PS≥2, non-platinum therapy (χ(2) p<0.05). CONCLUSION: EMT is infrequently seen in tumours of CUP. However, an adverse prognostic significance for patient outcome has been identified and may warrant studies of therapeutic targeting.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Primárias Desconhecidas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/epidemiologia , Neoplasias Primárias Desconhecidas/patologia , Fator 3 de Transcrição de Octâmero/metabolismo , Fenótipo , Prognóstico , Fatores de Transcrição da Família Snail , Análise Serial de Tecidos , Fatores de Transcrição/metabolismo , Vimentina/metabolismo
10.
Clin Lung Cancer ; 11(1): 30-5, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20085865

RESUMO

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rapidly progressive tumor that is increasing in frequency worldwide. Treatment options are limited, and response to chemotherapy is poor. The aim of this phase II study was to evaluate the activity of the carboplatin/pemetrexed combination as first-line chemotherapy in patients with unresectable MPM. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed MPM and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Treatment consisted of pemetrexed 500 mg/m2 and carboplatin area under the concentration-time curve of 5 mg/mL/min, both administered on day 1 of a 21-day cycle. The treatment continued until 6 cycles were completed or until unacceptable toxicity or disease progression were observed. RESULTS: A total of 62 patients were enrolled. Of these patients, 18 (29%) had a confirmed partial response, whereas the disease remained stable in 34 patients (54.9%) and progressed in 10 patients (16.1%). The median overall survival (OS) was estimated at 14 months (95% CI, 11.8-16.2 months), and the median time to progression was 7 months (95% CI, 5.8-8.2 months). The difference in median OS between the epithelial histologic subtype (16 months) and the sarcomatoid subtype (11 months) was statistically significant. CONCLUSION: This study confirmed the activity of the carboplatin/ pemetrexed combination in the first-line treatment of patients with MPM. It is a viable option, especially in cases in which side effects are generally anticipated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Progressão da Doença , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Masculino , Mesotelioma/mortalidade , Mesotelioma/fisiopatologia , Pessoa de Meia-Idade , Pemetrexede , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/fisiopatologia , Taxa de Sobrevida , Resultado do Tratamento
11.
Acta Oncol ; 47(6): 1148-55, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18607872

RESUMO

INTRODUCTION: Taxane/platinum combinations exhibit synergistic cytotoxicity and activity against a broad range of solid tumours. We sought to optimise the regimen as a suitable outpatient palliative treatment for cancer of unknown primary (CUP). PATIENTS AND METHODS: Eligible CUP patients with adenocarcinoma or poorly differentiated carcinoma, performance status of 0-2, adequate organ function and assessable disease were treated with docetaxel 75 mg/m(2) and carboplatin at an area under the concentration time-curve (AUC) of 5, both as 30-minute intravenous infusions, every three weeks. Patients with isolated axillary adenopathy, squamous cell cervical or inguinal adenopathy and PSA or germ-cell serum tumour markers were excluded. RESULTS: Forty-seven patients entered the trial, 24 with predominantly nodal disease or non-mucinous peritoneal carcinomatosis (favourable risk) and 23 with visceral metastases (unfavourable risk). A median of 6 cycles of chemotherapy were administered, with relative dose intensities of both drugs >90%. Response rates were 32% (46% in favourable risk, 17% in unfavourable), comparable to the activity of paclitaxel/platinum regimes, though complete remissions were seen only in favourable risk patients. Granulocyte-colony stimulating factor support was used in a third of treatment cycles. Toxicity was mild and manageable, with grade 3-4 neutropenia in 26% of patients, febrile neutropenia in 7% and severe non-hematologic side-effects in less than 8% of patients. No toxic deaths or severe neurotoxicity were seen. Median time to progression (TTP) and overall survival (OS) were 5.5 and 16.2 months respectively. Survival was driven mainly by favourable-risk patients (22.6 months), as those with visceral metastases had a poor median survival of only 5.3 months. Good performance status and low-volume disease predicted for superior outcome, while docetaxel relative dose-intensity was a positive prognosticator only in favourable-risk patients. CONCLUSIONS: One-hour docetaxel/carboplatin is a convenient, safe and effective outpatient palliative treatment for CUP patients, providing meaningful survival prolongation only in favourable-risk patients. Insights in the molecular biology of CUP are needed for the development of targeted therapeutic manipulations of malignant resistance and progression.


Assuntos
Adenocarcinoma/tratamento farmacológico , Assistência Ambulatorial , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Pacientes Ambulatoriais , Cuidados Paliativos/métodos , Adulto , Idoso , Assistência Ambulatorial/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Carboplatina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Grécia , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Taxoides/administração & dosagem , Resultado do Tratamento
12.
J Pers Assess ; 90(4): 348-55, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18584443

RESUMO

The aim of this study was to investigate symptoms of anxiety and depression in testicular cancer survivors (TCSs) and to identify personality traits associated with psychological distress in these patients by means of the MMPI (Hathaway & McKinley, 1943). A total of 50 TCSs and 50 age-adjusted healthy men participated in the study, and we used the following self-report instruments: Montgomery-Asberg Depression Rating Scale (Montgomery & Asberg, 1979), Hamilton Anxiety Rating Scale (Hamilton, 1959, 1969), Spielberger's State-Trait Anxiety Inventory (Spielberger, 1970, 2005), and the MMPI. TCSs displayed higher rates on all psychopathology scales studied compared to controls, but the majority of the patients' scores were within the "normal range," indicating rather mild psychological distress. TCSs' MMPI profiles showed higher rates on Scales 1, 3, 6, and 9 compared to controls; and within the TCSs sample, symptoms of depression were most closely associated with Scales 3 and 5. Similarly, anxiety symptoms were mainly associated with Scale 3. These findings indicate that TCSs present mild symptoms of psychological distress, mainly anxiety and depressive symptoms, suggesting that careful assessment and consultation in TC patients is essential to help them deal with distress after treatment and to minimize possible risk factors.


Assuntos
Personalidade , Estresse Psicológico , Sobreviventes/psicologia , Neoplasias Testiculares/psicologia , Adulto , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade
13.
BMC Cancer ; 6: 228, 2006 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-16999858

RESUMO

BACKGROUND: Surgery can cure a significant percentage of ovarian carcinoma confined to the pelvis. Nevertheless, there is still a 10-50% recurrence rate. We administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian carcinoma. METHODS: Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175 mg/m2 and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3 weeks. RESULTS: Sixty-nine patients with no residual disease following cytoreductive surgery and minimal or modified surgical staging were included in this analysis. Grade 3 or 4 neutropenia occurred in 29.9% of patients, while neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78-96) and 79% (95% CI: 69-89), respectively. Significantly fewer patients with stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with only one of these two factors (73% vs 92%, p = 0.03). CONCLUSION: Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3 may benefit from more extensive treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Grécia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
14.
Urology ; 66(2): 382-5, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16098366

RESUMO

OBJECTIVES: To evaluate the safety profile and therapeutic value of the combination of estramustine, mitoxantrone, and vinorelbine in the treatment of hormone-refractory prostate cancer. METHODS: Fifty-two patients with hormone-refractory prostate cancer were included in the study. Median age was 70 years (range, 49 to 100 years), World Health Organization performance status ranged from 0 to 2. The treatment schedule consisted of estramustine capsules (140 mg 3 times daily on days 1 to 3 and days 8 to 10 per os), intravenous mitoxantrone (12 mg/m2 on day 2), and intravenous vinorelbine (25 mg/m2 on day 2 and day 9), given in a 3-week cycle. RESULTS: Thirty-one percent of patients with measurable soft-tissue disease demonstrated an objective response, which included six complete and ten partial responses in all involved organs (bone responses not included). Twenty-nine patients (56%) had a greater than 50% reduction in serum prostate-specific antigen level. The median duration of response was 6.9 months, and the median survival for all patients was 14.5 months. CONCLUSIONS: The combination of estramustine, vinorelbine, and mitoxantrone is safe, well tolerated, and relatively active in patients with hormone-refractory prostate cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estramustina/administração & dosagem , Estudos de Viabilidade , Hormônios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Neoplasias da Próstata/mortalidade , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
15.
Anticancer Res ; 23(2C): 1687-91, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12820441

RESUMO

BACKGROUND: The addition of CPT-11 to 5FU/leucovorin resulted in survival benefit in patients with advanced colorectal cancer suggesting that this combination could be used successfully in the adjuvant setting. We studied the toxicity profile of postoperatively administered CPT-11 plus leucovorin (LV)-modulated 5FU and radiotherapy in patients with rectal cancer. PATIENTS AND METHODS: Thirty-seven patients with Dukes' B2 and C rectal adenocarcinoma were treated with CPT-11, 80 mg/m2 ii.v. over 90 minutes followed by LV 200 mg/m2 over 2 hours and 5FU 450 mg/m2 i.v.-bolus weekly for 4 weeks followed by a 2-week rest period. One cycle included 4 infusions. The first cycle of chemotherapy was followed by pelvic radiation to a total dose of 45 Gy to the whole pelvis and a boost of 5 Gy to the tumor bed. 5FU was administered daily as a rapid infusion during the first 3 as well as the last 3 days of radiotherapy. CPT-11 plus LV-modulated 5FU was continued for a total of 6 cycles or consent withdrawal. RESULTS: The main toxicity was reversible diarrhea (grade 3 and 4) in 9 (26%) patients during chemotherapy and in 3 (9%) patients during chemoradiotherapy. Furthermore, grade 3 leucopenia in 2 (6%) and 1 (3%) patient was observed during chemotherapy and chemoradiotherapy, respectively. CONCLUSION: This study provides evidence that adjuvant therapy using CPT-11 plus LV modulated 5FU and radiotherapy can be used in patients with rectal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante/efeitos adversos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
16.
Am J Clin Oncol ; 25(1): 23-30, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11823690

RESUMO

We conducted a phase III study in patients with advanced colorectal carcinoma (ACC). The total number of patients randomized from October 1993 until July 1998 was 192, whereas therapy was started on 179 and 158 (82.3%) have been evaluable. The treatment schedules consisted of weekly bolus administration for 6 weeks of 5-fluorouracil (5-FU), 600 mg/m2 (arm I) versus 5-FU (500 mg/m2) intravenous bolus and interferon-alpha, 5 MU subcutaneously, three times a week (arm II) versus leucovorin 200 mg/m2 in 2-hour infusion and 5-FU 500 mg/m2 intravenous bolus at the midtime of leucovorin infusion (arm III) followed by a 2-week rest period. Treatment was continued for six cycles or until progression. This study failed to show any superiority of the modulated 5-FU versus single administration of 5-FU. There were no significant differences between the three arms in the overall response rate (10.3% versus 11.3% versus 12.9%, p = 0.95), the time to tumor progression (median, 3.9 versus 3.8 versus 6.0 months, p = 0.59), or survival duration (median, 14.7 versus 12.4 versus 16.3 months, p = 0.71). The incidence of severe (grades III and IV) toxicity was significantly higher in patients in arm II and III (24.5% and 18.6%) versus arm I (6.0%) (p = 0.01). Because modulated 5-FU failed to show superiority versus 5-FU, new agents and new strategies are needed for the treatment of advanced colorectal carcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Análise de Sobrevida
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