Probably more than any country, Singapore has made significant investment into the biomedical enterprise as a proportion of its economy and size. This focus recently witnessed a shift towards a greater emphasis on translational and clinical development. Key to the realisation of this strategy will be Academic Medical Centres (AMCs), as a principal tool to developing and applying useful products for the market and further improving health outcomes. Here, we explore the principal value proposition of the AMC to Singapore society and its healthcare system. We question if the values inherent within academic medicine--that of inquiry, innovation, pedagogy and clinical exceptionalism--can be compatible with the seemingly paradoxical mandate of providing cost-effective or rationed healthcare.
Academic Medical Centers ; economics ; organization & administration ; Cost-Benefit Analysis ; Financing, Government ; Health Care Costs ; Health Care Rationing ; Quality of Health Care ; Singapore

Adenocarcinoma ; pathology ; therapy ; Choriocarcinoma, Non-gestational ; pathology ; therapy ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms ; secondary ; Middle Aged ; Neoplasms, Germ Cell and Embryonal ; pathology ; therapy ; Urinary Bladder Neoplasms ; pathology ; therapy ; Uterine Neoplasms ; pathology ; therapy

INTRODUCTIONAdvanced 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.

MATERIALS AND METHODSPatients 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; etiology ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; drug therapy ; etiology ; Male ; Middle Aged ; Prospective Studies ; Time Factors ; Treatment Outcome