http://repub.eur.nl/res/aut/40038/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/32013/ 2012-01-01T00:00:00Z Context: Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Objective: Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. Evidence acquisition: A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Evidence synthesis: Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Conclusions: Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio. http://repub.eur.nl/res/pub/28147/ 2010-01-01T00:00:00Z Interferon (IFN) is a cytokine with a long history of use as immunotherapy in the treatment of various solid tumours and haematological malignancies. The initial use of IFN in cancer therapy was based on its antiproliferative and immunomodulatory effects, and it has been shown more recently to have cytotoxic and anti-angiogenic properties. These features make it a rational anticancer therapy; however, advances in our understanding of the molecular mechanisms involved in cancer development and growth and the availability of effective, alternative therapies have led to IFN therapy being superseded in many cancers. IFN is still commonly used in renal cell carcinoma (RCC), melanoma and myeloproliferative disorders, in which its optimal dose and treatment duration remain to be established despite extensive clinical experience. Preclinical studies of the mechanism of action of IFN suggest that different antitumour effects are relevant at different doses, providing a rationale to explore the use of different dose regimens of IFN, particularly when combined with other therapies. In particular, the advent of novel anti-angiogenic therapies in RCC means that the role of IFN needs to be re-examined with a focus on how best to maximise efficacy and minimise toxicity when used with these agents. This review will focus on the therapeutic use of IFN in these disorders, provide an overview of available data and consider what the data suggest regarding the potential optimal use of IFN in the future.