Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma
Annals of the Academy of Medicine, Singapore
; : 554-558, 2008.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-358777
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>INTRODUCTION</b>Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant. We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma. The trial considered a "no further interest" response rate of 10% and a target response rate of 30%. Utilising a Simon's minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required. Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed.</p><p><b>MATERIALS AND METHODS</b>Patients with advanced HCC, diagnosed based on histology or by World Health Organization (WHO) criteria, were administered gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on day 1 and day 8 of a 21-day schedule. Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy.</p><p><b>RESULTS</b>The trial was stopped early due to a lack of efficacy. A total of 15 patients were accrued. Twelve patients were hepatitis B positive and the other 3 patients were negative for both hepatitis B and C. Only 1 patient had a history of prior heavy alcohol use. Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis. This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities. Only 5 of 15 patients experienced grade III toxicities (nausea and emesis, 1 patient; anemia, 1 patient; thrombocytopenia, 1 patient; and neutropaenia, 2 patients). Only 1 patient experienced a partial response to the combination of gemcitabine and cisplatin. A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy. The median time to progression was 6 weeks. The progression-free curve showed a sharp descent in the initial part of the study, suggesting that many patients had disease progression after enrollment. The median overall survival was 18 weeks.</p><p><b>CONCLUSION</b>The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HCC.</p>
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
Problema de saúde:
Meta 3.8 Atingir a cobertura universal de saúde
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fatores de Tempo
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Estudos Prospectivos
/
Cisplatino
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Resultado do Tratamento
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Carcinoma Hepatocelular
/
Intervalo Livre de Doença
/
Usos Terapêuticos
/
Desoxicitidina
/
Tratamento Farmacológico
Tipo de estudo:
Estudo observacional
/
Estudo prognóstico
Limite:
Adulto
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Annals of the Academy of Medicine, Singapore
Ano de publicação:
2008
Tipo de documento:
Artigo