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1.
Anticancer Res ; 40(1): 305-313, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892581

RESUMO

BACKGROUND: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. PATIENTS AND METHODS: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. RESULTS: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. CONCLUSION: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.


Assuntos
Neoplasias/complicações , Trombose/etiologia , Trombose/terapia , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Fatores de Risco
2.
J Geriatr Oncol ; 10(1): 143-148, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30366852

RESUMO

BACKGROUND: Although colorectal cancer (CRC) is a disease of the older patients, older patients are under-represented from randomized trials. Herein we conducted a retrospective analysis for the effect of panitumumab in the management of older patients (≥65 years) patients with metastatic CRC (mCRC) in the Hellenic Oncology Research Group's (HORG) database. METHODS: Τhe efficacy of panitumumab-based chemotherapy as front-line treatment in older patients with mCRC was assessed. RESULTS: In total, 110 older patients with KRAS exon 2 wild type tumors were treated with chemotherapy plus panitumumab. The median age was 74 years; 69.9% of the patients were male, with left-sided primary tumors (78.2%), ECOG Performance Status 0-1 (95.4%) and median number of metastatic sites 2. Sixty-two (Overall Response Rate-ORR: 56.4%; 95% CI: 48.8%-68.1%) achieved an objective response, while 21 (19.1%) had stable disease. Median Progression free survival (PFS) was 9.4 months (95% CI: 7.8-11.0 months) and median Overall survival (OS) 23.0 months (95% CI: 20.6-25.3 months). Additionally, a statistically significant difference in ORR (62.7% vs. 33.3%; p = .014), median PFS (12.9 vs. 5.7 months; p = .001) and median OS (31.6 vs. 16.7 months; p < .001) was observed in patients with left-sided compared to right-sided primary tumor. There was no treatment-related death. Grade 3-4 toxicities were neutropenia (8.9%) and diarrhea (14.5%) whereas skin rash grade 2 or 3 was recorded in 41.1% and 10.7%, respectively. CONCLUSIONS: The results of this retrospective study provide the evidence that combination chemotherapy plus panitumumab is active and well tolerated in older patients with mCRC.

3.
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
4.
Ann Gastroenterol ; 29(4): 390-416, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27708505

RESUMO

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

5.
Mol Clin Oncol ; 4(5): 723-727, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27123270

RESUMO

Malignant myoepithelioma of the breast is an extremely rare tumor composed entirely or almost entirely of malignant spindle cells with myoepithelial differentiation. Only a limited number of case reports have been descibed to date; therefore the biological behavior and treatment outcomes of this rare tumor have not been clearly determined. Herein, we present a case of a 74-year-old woman who was admitted with inflammatory-like cancer of the breast, presenting with invasion of the chest wall and axillary lymph node metastasis at the time of diagnosis. The histological examination revealed a tumor composed of epithelioid and spindle cells with moderate to marked nuclear atypia, with foci of hemorrhage and necrosis. The tumor cells were immunoreactive for vimentin, p63, p53, CD10, cytokeratin (CK)8/18, CKAE1-3 and S-100. Finally, a diagnosis of myoepithelial carcinoma of the breast was established. Neoadjuvant chemotherapy was first administered and proved to be ineffective. Due to locoregional progression that was associated with the development of an abscess and subsequent excessive bleeding, a palliative mastectomy was performed. Postoperatively, one more cycle of systemic chemotherapy was administered. However, the patient experienced an early relapse to the chest wall and succumbed to septic shock due to persistent local infection. The aggressiveness and chemoresistance of the tumor in this case was consistent with the existing bibliography.

6.
Ann Gastroenterol ; 29(2): 103-26, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27064746

RESUMO

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

7.
Ann Gastroenterol ; 29(1): 3-17, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26752945

RESUMO

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized.

8.
Ann Gastroenterol ; 29(1): 18-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26751386

RESUMO

Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered.

9.
Breast Cancer Res Treat ; 148(3): 591-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25399229

RESUMO

Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive early breast cancer. However, which is the preferable taxane in a dose-dense regimen remains unknown. We conducted a randomized study to compare the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with node-positive early breast cancer. Following surgery women with HER2-negative breast cancer and at least one infiltrated axillary lymph node were randomized to receive four cycles of FEC (700/75/700 mg/m(2)) followed by four cycles of either paclitaxel (175 mg/m(2)) or docetaxel (75 mg/m(2)). All cycles were administered every 14 days with G-CSF support. The primary endpoint was disease-free survival (DFS) at 3 years. Between 2004 and 2007, 481 women were randomized to paclitaxel (n = 241) and docetaxel (n = 240). After a median follow-up of 6 years, 51 (21%) and 48 (20%) women experienced disease relapse (p = 0.753) and there was no significant difference in DFS between the paclitaxel- and docetaxel-treated groups (3-year DFS 87.4 vs. 88.3%, respectively; median DFS not reached; p = 0.633). Toxicities were manageable, with grade 2-4 neutropenia in 21 versus 31% (p = 0.01), thrombocytopenia 0.8 versus 3.4% (p = 0.06), any grade neurotoxicity 17 versus 7.5% (p = 0.35) and onycholysis 4.9 versus 12.1% (p = 0.03) for patients receiving paclitaxel and docetaxel, respectively. There were no toxic deaths. Dose-dense paclitaxel versus docetaxel after FEC as adjuvant chemotherapy results in a similar 3-year DFS rate in women with axillary node-positive early breast cancer. Due to its more favorable toxicity profile, paclitaxel is the taxane of choice in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Resultado do Tratamento
10.
BMJ Open ; 4(5): e004652, 2014 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-24859998

RESUMO

OBJECTIVES: Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection of KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations. SETTING: Diagnostic molecular laboratory located in Athens, Greece. PARTICIPANTS: 2425 patients with colorectal cancer participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: 2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15) analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing. RESULTS: KRAS exon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2 wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF mutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method. CONCLUSIONS: The HRM method developed was shown to be a reliable method for KRAS, NRAS and BRAF mutation detection. Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was observed between Greek and Romanian patients with colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos de Coortes , Grécia , Humanos , Técnicas de Diagnóstico Molecular/métodos , Desnaturação de Ácido Nucleico , Romênia
11.
Anticancer Drugs ; 25(7): 841-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24625457

RESUMO

An appreciable percentage of patients with relapsed/refractory germ-cell tumors (GCTs), candidates for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (HCT), fail to mobilize adequate hematopoietic stem cells (HSCs) numbers with granulocyte colony-stimulating factor (G-CSF)±salvage chemotherapy. Plerixafor has shown a potential to mobilize adequate CD34+HSCs numbers in this context. Here, we applied plerixafor in combination with G-CSF after salvage chemotherapy in 'poor' mobilizers with relapsed/refractory GCTs for HDC+HCT. Patients with relapsed/refractory GCTs (n=10) received salvage paclitaxel-ifosfamide-cisplatin (TIP) chemotherapy+G-CSF to mobilize adequate HSCs to support HDC, mainly with two courses of high-dose thiotepa-etoposide-carboplatin (TEC). Patients failing to achieve the minimum collection threshold of 2.0×10/kg CD34+ cells, to support at least one cycle of HDC, were administered plerixafor before the anticipated HSC collection during subsequent cycle(s). Overall, seven patients mobilized adequate CD34+ cells (>5.0×10/kg) aiming to support two cycles of HDC. Three patients did not mobilize adequate numbers of CD34+ cells after previous G-CSF plus salvage TIP, and plerixafor was added in subsequent cycle(s). This led to a collection of adequate CD34+ cells, able to support HDC with TEC (1-2 cycles). Hematopoietic engraftment for neutrophils (absolute neutrophil count>500/µl) and platelets (platelet count>20 000/µl) with plerixafor-mobilized HSCs occurred after a median of 9 and 14 days, respectively. Salvage TIP+G-CSF leads to successful HSC mobilization in patients with less heavily pretreated GCTs, whereas the addition of plerixafor to G-CSF+TIP led to mobilization of adequate HSCs that supported autografting after one to two TEC cycles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Neoplasias Embrionárias de Células Germinativas/terapia , Adulto , Cisplatino/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Masculino , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Paclitaxel/administração & dosagem , Transplante Autólogo , Adulto Jovem
12.
Cancer Chemother Pharmacol ; 69(2): 351-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21748359

RESUMO

PURPOSE: To assess the antitumor activity and toxicity of gemcitabine, cisplatin, and docetaxel (GCD) regimen in patients with locally advanced or metastatic urothelial cancer. PATIENT AND METHODS: Chemotherapy-naïve patients, aged ≤70 years with measurable or evaluable disease and a performance status (PS) of 0-2 were treated with sequential cisplatin 80 mg/m(2) (d1), gemcitabine 1,100 mg/m(2) (d1 and d14), and docetaxel 80 mg/m(2) (d14) every 28 days. RESULTS: Sixty patients with an ECOG PS of 0-2 were enroled. Most (71.7%) patients had stage IV disease. A median number of 4 chemotherapy cycles per patient (range, 1-9) was administered. Eight (13.3%) patients achieved a CR and 16 (26.7%) a partial response (PR) (intention-to-treat: ORR 40%; 95% CI 27.6-52.4%). Thirteen (21.7%) and 23 (38.3%) patients experienced stable and progressive disease, respectively. The median time to progression (TTP) was 7.7 months (range, 0.7-43.4), and the median overall survival 21.4 months (range, 0.7-68.6). Grade 3 and 4 neutropenia occurred in 27 (45%) patients and grade 3 and 4 thrombocytopenia in five (8.3%). Three (5%) patients developed febrile neutropenia. There were no treatment-related deaths. Severe non-haematological toxicity was infrequent. CONCLUSIONS: The GCD combination is an active and well-tolerated regimen in patients with chemotherapy-naive locally advanced or metastatic TCC and merits to be further investigated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Músculos/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Docetaxel , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Náusea/induzido quimicamente , Invasividade Neoplásica , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
13.
Hell J Nucl Med ; 14(2): 163-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21761020

RESUMO

Paragangliomas, also described as ectopic pheochromocytomas are infrequent neuroectodermal neoplasms that could be found wherever paraganglionic tissue exists. We present a rare case of a manifold non-functional primary hepatic paraganglioma in a 71 years old female. The combination of structural computed tomography and magnetic resonance imaging and of a functional modality, octreotide scan supported diagnosis. The role of nuclear medicine is crucial because it may help to determine future treatment in cases where there is suspicion of this tumour. However it has certain limitations, largely related to the physiological radionuclidic biodistribution. This case is described because of its relative rarity and also to emphasize the need to be studied by multidisciplinary collaboration.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Idoso , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Humanos , Radioisótopos do Iodo , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Doenças Raras/diagnóstico , Doenças Raras/diagnóstico por imagem , Somatostatina/análogos & derivados , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos
14.
Cancer Chemother Pharmacol ; 68(1): 63-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20830475

RESUMO

PURPOSE: To evaluate efficacy and toxicity of a combination of pegylated liposomal doxorubicin and irinotecan in patients with refractory small-cell lung cancer. PATIENTS AND METHODS: Thirty-one patients with early relapse after first-line therapy with cisplatin/etoposide were treated with pegylated liposomal doxorubicin 15 mg/m(2) and irinotecan 125 mg/m(2) on days 1 and 15. Treatment was repeated every 28 days. RESULTS: A total of 144 chemotherapy courses were administered. All patients were evaluable for toxicity and twenty-six (84%) for response. Grade 3 neutropenia occurred in two (6.5%) patients and grade 1 thrombocytopenia in one (3.2%). Fatigue was the most frequent grade 3 non-hematologic toxicity and was observed in seven patients (23%). Four (12.9; 95% CI: 1.1-24.7%) patients achieved a partial response, and disease stabilization was observed in additional two (6.5%) patients (Tumor Growth Control: 19.4; 95% CI: 5.5-33.3%). The median TTP was 2.03 months, and the median survival time was 3.16 months. CONCLUSIONS: The combination of pegylated doxorubicin and irinotecan is very well tolerated but with modest activity in patients with refractory SCLC.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Doxorrubicina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Progressão da Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Resultado do Tratamento
15.
Oncology ; 78(5-6): 356-60, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20798557

RESUMO

PURPOSE: To evaluate the efficacy and tolerability of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11) as first-line treatment of advanced biliary tract cancer. PATIENTS AND METHODS: Patients with histologically confirmed nonresectable biliary adenocarcinoma were treated with oxaliplatin (85 mg/m(2)) and irinotecan (200 mg/m(2)) every 3 weeks. RESULTS: Twenty-eight patients were enrolled between May 2005 and March 2009. The overall objective response rate was 17.9% with an additional 21.4% of patients with stable disease (disease control rate 39.3%). The median overall survival time was 9.2 months (95% CI 5.8-12.5) and the median progression-free survival time 2.7 months (95% CI 2.2-3.2). Grades 3 and 4 neutropenia occurred in 1 (3.6%) and 4 (14.3%) patients, respectively, and febrile neutropenia in 3 (10.7%). Grade 3-4 diarrhea was observed in 2 (7.1%) patients and grade 3 asthenia in 1 (6%). There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and irinotecan has a modest antitumor activity with manageable toxicity as first-line treatment in metastatic cancer of the biliary tract and therefore it cannot be recommended as front-line treatment for unresectable biliary tract cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Camptotecina/análogos & derivados , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Ampola Hepatopancreática/patologia , Antineoplásicos/toxicidade , Antineoplásicos Fitogênicos/toxicidade , Neoplasias do Sistema Biliar/patologia , Camptotecina/uso terapêutico , Camptotecina/toxicidade , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Neoplasias do Ducto Colédoco/tratamento farmacológico , Neoplasias do Ducto Colédoco/patologia , Feminino , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Compostos Organoplatínicos/toxicidade , Oxaliplatina
16.
Oncology ; 78(3-4): 229-36, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20523083

RESUMO

BACKGROUND: Non-platinum-containing regimens have been proposed as alternatives to platinum-based doublets in the first-line treatment of patients with non-small cell lung cancer (NSCLC). However, conflicting results about their equivalence have been reported. METHODS: We reviewed the records of patients enrolled in randomized controlled first-line trials conducted by the Hellenic Oncology Research Group from February 1997 to September 2006. The outcome of patients treated with first-line non-platinum-based chemotherapy who received platinum-based chemotherapy upon progression (cohort A) or platinum-based first-line chemotherapy followed by non-platinum-containing second-line chemotherapy (cohort B) was retrospectively analyzed. RESULTS: Two-hundred and sixty-seven patients were identified in cohort A, and 123 in cohort B. Median follow-up time was 12.5 and 15.7 months for cohorts A and B. A significantly higher response rate and time to tumor progression (TTP) was recorded for patients treated with platinum-based compared to those receiving non-platinum-based first-line chemotherapy (45.5 vs. 21.3%, p < 0.0001 and 5.8 vs. 3.1 months, p= 0.002, respectively). Platinum-based regimens administered as second-line treatment resulted in a 13.1% response rate. TTP for second-line chemotherapy did not differ significantly between the two cohorts. Median overall survival was 13.3 and 15.7 months for cohorts A and B (p = 0.538). CONCLUSION: Both sequences resulted in similar efficacy in terms of overall survival. Encouraging median survival was achieved for selected patients with NSCLC who received both first- and second-line chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Platina/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
Thyroid ; 20(6): 597-600, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20553195

RESUMO

BACKGROUND: Although thyroid carcinoma is more indolent than other solid tumors, distant metastatic disease due to differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC) is often refractory to treatment and thus a challenge for clinicians. New agents such as tyrosine kinases inhibitors have been introduced recently for therapy of metastatic thyroid cancer but they have toxic side effects as well as therapeutic benefits. The objective of this study was to determine the hematologic toxicities of sunitinib, a multiple receptor tyrosine kinases inhibitor, when used to treat progressive, advanced DTC and MTC. METHODS: Six patients with DTC and four with MTC who were treated with sunitinib were retrospectively studied for short-term hematological toxicities related to red cell and platelet mass and the major leukocyte series. RESULTS: Before the start of sunitinib treatment, 5 of 10 patients (50%) received external beam radiation therapy and 6 of 10 (60%) had hematologic abnormalities. During sunitinib treatment, some grade of neutropenia was noted in 6 of 10 patients (60%), anemia in 1 of 10 (10%), thrombocytopenia in 7 of 10 (70%), and lymphocytopenia in 4 of 10 (40%). Monocytopenia was present in all 10 patients. Considering grades 3 and 4 hematologic toxicities, neutropenia was noted in 2 of 10 (20%), anemia in 1 of 10 (10%), and thrombocytopenia in 1 of 10 (10%). There was no grade 3 or 4 lymphocytopenia, but we noted a 52.4% (+/-17.47% standard deviation) decrease in monocyte counts. All patients had macrocytosis, despite normal circulating folate and cobalamin levels. In one patient with DTC, sunitinib had to be permanently discontinued because of hematological toxicity. CONCLUSIONS: Despite the fact that most patients with DTC had received large doses of radioiodine and some had received external beam radiation therapy, both of which have myelosuppressive potential, treatment with sunitinib was well tolerated in most patients with DTC as well as in the patients with MTC. These results are encouraging, but, as our series was small and did not evaluate efficacy, more extensive studies in DTC and MTC are needed to determine the possible roles of sunitinib in these very different tumors.


Assuntos
Carcinoma Medular/tratamento farmacológico , Inibidores Enzimáticos/efeitos adversos , Sistema Hematopoético/efeitos dos fármacos , Indóis/efeitos adversos , Pirróis/efeitos adversos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Diferenciação Celular , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Sunitinibe , Neoplasias da Glândula Tireoide/patologia
18.
Breast Cancer Res Treat ; 119(1): 95-104, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19636702

RESUMO

A randomized multicenter phase III study was conducted to compare the sequential docetaxel followed by epirubicin/cyclophosphamide combination with that of FEC regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer. Seven hundred and fifty-six women with axillary lymph node-positive breast cancer were randomized to receive either 4 cycles of docetaxel (100 mg/m(2)) followed by 4 cycles of epirubicin (75 mg/m(2)) plus cyclophosphamide (700 mg/m(2)) (experimental arm) or 6 cycles of FEC (epirubicin 75 mg/m(2), cyclophosphamide 700 mg/m(2), and 5-fluorouracil 700 mg/m(2); control arm). All regimes were administered every 3 weeks. The primary end point was five-year disease-free survival (DFS). After a median follow-up period of 5 years, 233 (30.8%) relapses had occurred (108 and 125 in the experimental and control arms, respectively; P = 0.181). The five-year DFS was 72.6% (95% CI 63.8-81.3%) and 67.2% (95% CI 58.0-76.4%) for women randomized in the experimental and control arms, respectively (P = 0.041; log rank test). There was no difference in the overall survival between the two arms (83.8 and 81.4% in the experimental and control arms, respectively; P = 0.533). The experimental arm was associated with increased neutropenia requiring administration of granulocyte colony-stimulating factor in 90.5% of the patients as compared with 74.1% in the control arm (P = 0.0001). The sequential docetaxel followed by epirubicin/cyclophosphamide adjuvant chemotherapy regimen resulted in improved five-year DFS in women with axillary node-positive early breast cancer at the expense of increased but manageable myelotoxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Metástase Linfática , Adulto , Idoso , Neoplasias da Mama/metabolismo , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
19.
Int J Cardiol ; 122(3): 195-201, 2007 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-17289172

RESUMO

BACKGROUND: Cardiac function impairment is a known side effect of epirubicin-based chemotherapy. Activation of natriuretic peptides is demonstrated in patients with heart failure. AIMS: To identify prospectively the cardiotoxic profile of epirubicin-based chemotherapy in breast cancer patients and to evaluate the sensitivity of proANP and NT-proBNP as early biochemical markers of cardiac dysfunction. METHODS: Forty cancer patients divided in two nonrandomized groups received either epirubicin and paclitaxel (Group A, n=26) or mitoxantrone and docetaxel (Group B, n=14). Control groups, Group C (n=13) and Group D (n=20), consisted of female patients with heart failure and healthy women respectively. Natriuretic peptides and LVEF were determined in all patients. RESULTS: A statistically significant difference was recorded regarding LVEF before and after treatment in Group A patients (p=0.0001). Three patients had a significant LVEF decline between 10% and 18% from baseline values, while three reached an LVEF value below 50%. All of them presented an increase in proANP and NT-proBNP values (mean increase 270.31+/-124 fmol/ml and 303.57+/-108 fmol/ml, respectively). A significant correlation between the increase in plasma proANP (r=0.8, p<0.0001), as well as NT-proBNP (r=0.7, p<0.0001) and the decrease in LVEF was observed. Regarding Group A, levels of proANP increased from 192.25 fmol/ml before treatment to 287.84 fmol/ml after treatment (p=0.0001), whereas NT-proBNP increased from 152.50 to 242 fmol/ml (p<0.0001) respectively. During follow up, two Group A patients developed congestive heart failure twelve and fourteen months after the completion of chemotherapy respectively. A significant LVEF decline was recorded in both patients during the episode. Regarding Group B, no statistically significant differences were demonstrated. CONCLUSION: ProANP and NT-proBNP levels might be used as reliable and sensitive markers in the detection of early cardiac impairment caused by epirubicin-based chemotherapy.


Assuntos
Antineoplásicos/toxicidade , Fator Natriurético Atrial/sangue , Neoplasias da Mama/sangue , Doenças Cardiovasculares/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Adulto , Biomarcadores/sangue , Neoplasias da Mama/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Oncology ; 70(4): 280-4, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17047399

RESUMO

BACKGROUND: A multicenter phase II study was conducted in order to evaluate the efficacy and safety of oxaliplatin as first-line treatment of patients with locally advanced or metastatic carcinoma of the biliary tract. PATIENTS AND METHODS: Twenty-nine chemo-naïve patients with locally advanced or metastatic biliary tract carcinoma received oxaliplatin 130 mg/m(2) i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. RESULTS: An objective response (3 complete responses, 3 partial responses) was achieved in 6 patients (20.6%, 95% CI 5.95-35.4). Disease control (complete response, partial response and stable disease) was observed in 14 patients (48.2%). The median time to tumor progression was 3 months (range 0.7-39) and the median overall survival was 7 months (range 1-39). The 1-year survival rate was 32%. Toxicity was mild. CONCLUSION: Oxaliplatin is an active agent against biliary tract carcinoma and therefore should be further investigated in combination with other cytotoxic drugs.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
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