Background: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. Methods: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were  collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. Results: The addition of bevacizumab to capecitabine monotherapy cost  approximately $192,156 (95% confidence interval [CI], $135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to $149,455 (95% CI, $100,356 to $245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95% CI, $106,703 to $233,225). Conclusions: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.Roche Products Pty Lt

Carter, Hannah

Zannino, Diana

Simes, R John

Schofield, Deborah J

Howard, Kirsten

Zalcberg, John R

Price, Timothy J

Tebbutt, Niall C

English

Dissertação de Mestrado em Biologia Celular e Molecular, apresentada ao Departamento de Ciências da Vida da Universidade de Coimbra.Malaria has long been a threat to survival and persistently challenging at vaccine development. With a stuttering rise
in drug resistant strains of the human parasites - Plasmodium falciparum and Plasmodium vivax, it is of paramount
concern to identify new drug targets, which would render infection unsustainable at the earliest stage. As an
essential co-factor iron has a critical role in virtually every cell from the simplest prokaryotes to complex eukaryotes.
In humans, the fine tuning of iron homeostatic mechanism also dictates the outcomes to various infections.
Plasmodium with its intricate life cycle and immense replication potential exhibits a high demand for iron at multiple
stages during its development. During its intra-erythrocytic development Plasmodium has several possible iron
reservoirs at its disposal in the host cell such as the iron bound in ferritin, the cytosolic labile iron pool and
hemoglobin. The parasite’s mechanism for iron uptake from the host and, its storage still remain shrouded due to
the complexity in relating genome sequence of Plasmodium spp. to specific proteins and function. In this thesis
project we have attempted to explore the function of two novel iron transporters in Plasmodium: Divalent metal
transporter (DMT1) and Vacuolar iron transporter (VIT) homologues and, investigate the effect of compromise of
their function on parasite development and virulence. Understanding the iron transport mechanism will shed some
light on possible methods to target such machinery, if found essential.A malária continua a ser uma ameaça à sobrevivência e persiste ao desafio da formulação de uma vacina. Com o
aumento da prevalência das estirpes de Plasmodium falciparum e Plasmodium vivax resistentes aos fármacos
disponíveis, torna-se cada vez mais relevante a identificação de novos alvos moleculares para o desenvolvimento de
fármacos que inibam a infeção em fases precoces. O ferro, um co-factor essencial, tem um papel fundamental em
virtualmente todas as células, desde o mais simples procariota até ao mais complexo eucariota. No Homem, a
regulação da homeostase do ferro determina o resultado de várias infeções. Dado o seu ciclo de vida complexo e o
seu grande potencial replicativo, Plasmodium spp. requerem uma grande disponibilidade ferro durante o seu
desenvolvimento. Durante a sua maturação nos eritrócitos, Plasmodium tem na célula hospedeira várias reservas de
ferro disponíveis, tais como, o ferro ligado à ferritina, o ferro livre no citosol e o ferro contido na hemoglobina. Os
mecanismos utilizados pelo parasita na obtenção de ferro a partir do hospedeiro e no seu armazenamento
continuam elusivos. Um obstáculo reside em parte na dificuldade em relacionar uma dada sequência genómica
de Plasmodium spp. com a função da proteína resultante. Neste trabalho, tentámos explorar a função de dois
transportadores de ferro identificados em Plasmodium: o Transportador de metais divalentes (do inglês, DMT) e o
Transportador vacuolar de ferro (do inglês, VIT). Nesse âmbito estudámos o efeito da disrupção da sua função no
desenvolvimento e na virulência do parasita. A melhor compreensão desta maquinaria do parasita, se considerada
essencial, elucidará possíveis métodos para a modular e utilizar como alvo terapêutico

Lahree, Aparajita

Estudo Geral

Characterizing Iron transporters in Plasmodium species

Sydney eScholarship