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1.
Ann Oncol ; 31(2): 228-235, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959339

RESUMO

BACKGROUND: Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. PATIENTS AND METHODS: Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m2 i.v., days 1-4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m2 to 80 mg/m2. RESULTS: The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06-2.98; P = 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79-1.75; P = 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. CONCLUSION: EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Receptores ErbB/genética , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/efeitos adversos , Humanos , Panitumumabe , Estudos Prospectivos , Resultado do Tratamento
2.
Ann Oncol ; 23(11): 2827-2834, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22734012

RESUMO

BACKGROUND: This prospective multicentre phase II trial assessed the feasibility and efficacy of perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in patients with gastro-oesophageal adenocarcinoma. METHODS: Patients with curatively resectable adenocarcinoma of the stomach, the gastro-oesophageal junction or the lower third of the oesophagus were enrolled. Patients received docetaxel 75 mg/m(2) plus cisplatin 60 mg/m(2) (day 1), followed by oral capecitabine 1875 mg/m(2) divided into two doses (days 1-14) every 3 weeks. There were three cycles preoperatively and three cycles postoperatively. The primary end point was the R0 resection rate. RESULTS: Fifty-one patients were recruited and assessed for feasibility and efficacy. 94.1% of patients received all three planned cycles preoperatively, and 52.9% received three cycles postoperatively. The R0 resection rate was 90.2%. 13.7% of patients showed complete pathological remission (pCR). Toxicity was acceptably tolerable. Without prophylactic granulocyte colony-stimulating factor administration, neutropenic fever developed in 21.5% of patients preoperatively (grade 3 or 4) and in 11.1% of patients postoperatively. CONCLUSIONS: DCX is a safe and feasible perioperative regimen in the treatment of gastro-oesophageal adenocarcinoma with a high percentage of cycles delivered pre- and postoperatively, compared with standard practice. The high efficacy in terms of R0 resection rate and pCR is very promising.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Esquema de Medicação , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do Tratamento
3.
Br J Cancer ; 105(4): 505-12, 2011 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-21792201

RESUMO

BACKGROUND: No comparisons of different doses of docetaxel-capecitabine in patients with advanced gastric cancer have been performed. METHODS: Patients with previously untreated metastatic/locally advanced gastro-oesophageal or gastric adenocarcinoma were enrolled in a prospective multicentre phase II trial. Two sequential cohorts received docetaxel 75 mg m(-2) (day 1) plus capecitabine 1000 mg m(-2) twice daily (days 1-14) (cohort I) or docetaxel 60 mg m(-2) (day 1) plus capecitabine 800 mg m(-2) twice daily (days 1-14) (cohort II) every 3 weeks. The primary end point was confirmed overall response rate. RESULTS: In all, 91 patients were enrolled (cohort I, n=40; cohort II, n=51) and 87 were evaluable for efficacy (n=38, 49, respectively). Overall response rate was 50.0% in cohort I and 23.5% in cohort II (exploratory analysis, P=0.014). Median times to tumour progression and overall survival were 5.6 and 10.1 months in cohort I and 3.7 and 7.2 months in cohort II, respectively. Dose reductions for docetaxel and capecitabine were required in 50.0% and 57.5% of patients in cohort I and 11.8% and 15.7% in cohort II, respectively. CONCLUSION: Starting treatment with full doses and reducing promptly seems to be the more promisingly effective strategy than starting cautiously with lower doses. Docetaxel/capecitabine 75/2000 mg m(-2) is a manageable, convenient outpatient combination with promising efficacy against advanced gastric cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Capecitabina , Estudos de Coortes , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
5.
Ann Oncol ; 14(8): 1227-33, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12881384

RESUMO

BACKGROUND: Capecitabine is a rationally designed oral, tumor-activated fluoropyrimidine carbamate with high activity in metastatic breast cancer. This multicenter phase II study was designed to evaluate further the efficacy and safety of capecitabine in patients with metastatic breast cancer previously treated with a taxane-containing regimen. PATIENTS AND METHODS: All patients had to have documented progression after paclitaxel- or docetaxel-containing chemotherapy. Treatment comprised 3-week cycles of oral capecitabine 1250 mg/m(2) twice-daily for 14 days followed by a 7-day rest period. RESULTS: One hundred and thirty-six patients were enrolled. Disease stabilization occurred in 63 patients (46%) and the overall response rate was 15% (95% confidence interval 10% to 23%), providing an overall tumor control rate of 62%. Median time to progression was 3.5 months, median duration of response was 7.5 months and median overall survival was 10.1 months. Capecitabine was generally well-tolerated: most treatment-related adverse events were grade 1/2 in intensity; grade 3/4 treatment-related adverse events were hand-foot syndrome (13%), diarrhea (8%), vomiting (4%) and nausea (3%). There were no treatment-related deaths. CONCLUSIONS: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer. Due to its favorable safety profile and convenient oral administration, capecitabine can be given as an outpatient therapy. Capecitabine should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Taxoides , Administração Oral , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Capecitabina , Intervalos de Confiança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/análogos & derivados , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Probabilidade , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento
6.
Eur J Cancer ; 39(11): 1511-6, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12855256

RESUMO

Alveolar soft part sarcoma (ASPS) is a rare tumour. Published series about treatment and outcome are scarce. Conclusive data about the response to chemotherapy are not available. The aim of this study was to analyse the efficacy of palliative chemotherapeutic treatment options and the incidence and mode of presentation of brain metastases. We retrospectively analysed our own sarcoma data-base and reviewed the literature. From our registry containing 757 patients, we identified 8 patients with ASPS. From the literature, 47 cases of adult patients and 13 children with sufficient data about chemotherapy were identified. Response to first-line chemotherapy in 68 patients was: complete remission (CR) 4%, partial remission (PR) 3%, stable disease (SD) 41%, progressive disease (PD) 51%. 285 patients with stage IV disease were evaluable for the analysis of metastatic sites. The incidence of brain metastases was 30.5% (87/285). Brain metastases were detected at a median interval of 48 months (range 0-396 months) after the primary diagnosis. Median survival after the diagnosis of brain metastases was 12 months. The median survival for patients with stage IV disease treated by chemotherapy was 36+ months (range 10-132 months) (31 patients evaluable) with a median follow-up of 46 months (range 10-135 months). ASPS shows a high incidence of brain metastases, at least 3 times higher than that of other soft tissue sarcomas. Chemotherapeutic regimens used for the treatment of other soft tissue sarcomas lack efficacy in ASPS. Staging investigations for ASPS should routinely include imaging of the brain. ASPS patients should not be treated with chemotherapy outside of controlled clinical trials. New targets for specific biologically-directed therapies need to be developed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Adulto , Neoplasias Encefálicas/secundário , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Indução de Remissão , Sarcoma Alveolar de Partes Moles/secundário , Análise de Sobrevida
7.
Onkologie ; 26(1): 63-5, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12624520

RESUMO

BACKGROUND: Metastatic gastric cancer is usually treated with cisplatin- and 5-FU-based chemotherapy regimens. There are good data for the combination regimen ECF (epirubicin, cisplatin and 5-FU), which is therefore often regarded as a reference treatment. Docetaxel shows promising activity against gastric cancer as single agent and in combinations. To develop a well-tolerable combination chemotherapy for an ambulant setting we initiated a randomized phase II study, comparing docetaxel and 5-FU continuous infusion (DF) with ECF. CASE REPORT: A 66-year-old patient with the history of a curatively resected gastric cancer 2 years previously presented with abdominal masses and lesions in his spleen. Histology proved metastases of gastric adenocarcinoma. The patient was treated with docetaxel (75 mg/m2, d1) and 5-FU continuous infusion (200 mg/m2/d, d1-21, q3w) within our study. Already after 2 cycles of chemotherapy he showed symptomatic improvement and partial remission of his tumor, which was confirmed after the 3rd cycle. In our ongoing study so far 50 patients are evaluable for response. Objective tumor response (CR + PR) could be documented in 44% of patients in the DF arm as well as in the ECF arm. CONCLUSION: Docetaxel and 5-FU continuous infusion is an active regimen which could possibly be used as an alternative to established treatment protocols.


Assuntos
Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/análogos & derivados , Neoplasias Esplênicas/secundário , Neoplasias Gástricas/tratamento farmacológico , Taxoides , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biópsia por Agulha , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Baço/patologia , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/patologia , Neoplasias Gástricas/patologia , Resultado do Tratamento
8.
Onkologie ; 25(6): 541-6, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12566899

RESUMO

OBJECTIVES: Aim of this study was to evaluate the feasibility and toxicity of oral trofosfamide given as maintenance therapy to adult patients with bone and soft tissue sarcomas following first or later line induction chemotherapy, and to determine the clinical efficacy in terms of impact on progression-free and overall survival. PATIENTS AND METHODS: 49 patients with locally advanced or metastatic high-grade soft tissue and bone sarcomas were identified retrospectively according to the inclusion criteria of the analysis. They were treated with oral trofosfamide at a dose of 100-150 mg per day continuously. All patients were pretreated with one or more lines of chemotherapy resulting in partial remission or stable disease. Patients were treated until progression of disease or unacceptable toxicity occurred. Progression- free and overall survival were measured from the beginning of maintenance therapy. RESULTS: Median follow-up for all patients was 33 months (range 10-98). Toxicity was mild and predominantly hematologic. Only 1 patient had to stop treatment due to renal toxicity. The median progression-free survival was 7 months with 27% of patients continuing maintenance treatment at 1 year. Median overall survival is 14 months. Patients with metastatic disease showed a median survival of 23 months from diagnosis of metastases. 3 patients with stable disease following induction chemotherapy reached partial remission while under trofosfamide maintenance. CONCLUSION: Oral maintenance therapy with trofosfamide is well-tolerated and seems to prolong progression-free and overall survival compared to the course of advanced soft tissue and bone sarcomas without maintenance chemotherapy.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Ciclofosfamida/análogos & derivados , Ciclofosfamida/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Ósseas/mortalidade , Ciclofosfamida/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Estudos Retrospectivos , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade
9.
Oncology ; 59(1): 14-7, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10895060

RESUMO

PURPOSE: This study was performed to investigate the activity and safety of high dose 5-fluorouracil (5-FU) given as a weekly 24-hour infusion in combination with folinic acid plus mitomycin C in patients with advanced gastric cancer. PATIENTS AND METHODS: Chemonaive patients with locally advanced inoperable, recurrent or metastatic gastric cancer were treated with 15 mg/m(2) i.v. mitomycin C as bolus on day 1 of a 7-week cycle followed by a 2-hour infusion of folinic acid (500 mg/m(2)) and a 24-hour infusion of 5-FU (2,600 mg/m(2)) given on days 1, 8, 15, 22, 29, and 36 as outpatient treatment. RESULTS: Thirty evaluable patients (median age 58 years and median ECOG performance status 1) received 1-4 cycles (median 3). 53% of the patients had liver metastases. Treatment-related toxicity was low with 10% of patients experiencing diarrhea >/=grade 3, 3% mucositis grade 3 and 3% nausea grade 3 (CTC). Hematological toxicity was mild with 13% thrombopenia grade 3 and no leukopenia grade 4. Eleven patients achieved a partial remission (major response rate 37%; 95% confidence interval 22-53%). Median time to progression was 5 months and median overall survival time was 7 months. CONCLUSION: This regimen is a well-tolerated outpatient treatment for patients with advanced gastric cancer with efficacy being comparable to other chemotherapy protocols.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Metástase Neoplásica
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