Expert opinion on investigational drugs
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There is convincing evidence that angiotensin II, through activation of the angiotensin II type 1 (AT1) receptor, is involved in the atherosclerotic process. Similarly, angiotensin receptor blockers decrease vascular inflammation, hypertrophy and thrombosis, which are the key components of the progression of atherosclerosis. In addition, in several animal models, angiotensin receptor blockade was able to inhibit atherosclerosis. ⋯ Contradictory results have been found on the reduction of the risk on myocardial infarctions and in-stent restenosis, although there is solid evidence for cerebroprotective effects of these receptor blockers. These differences may be related to the role of the AT2 receptor. This review discusses the role of angiotensin II and angiotensin receptor blockers in the atherosclerotic process and its translation into clinical practice.
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Expert Opin Investig Drugs · Jul 2007
Review Comparative StudyAromatase inhibitors in post-menopausal metastatic breast carcinoma.
To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR. ⋯ Weight gain, dyspnoea and peripheral oedema seem to be more frequent with MEG. At present, there is no proved overall survival difference in patients who are treated first with an AI and then with tamoxifen compared with the opposite sequence. In the metastatic setting, results are limited and are based on retrospective analyses.
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Expert Opin Investig Drugs · Jul 2007
ReviewBroadening the clinical use of platinum drug-based chemotherapy with new analogues. Satraplatin and picoplatin.
The three platinum-containing drugs that have been thus far approved by the FDA - cisplatin, carboplatin and oxaliplatin - have had a significant effect in the treatment of patients with some malignancies such as testicular, ovarian and colorectal cancer. However, much more remains to be achieved to widen the therapeutic use of this important class of drug, either via further analogue development or by judicious use of combining the existing drugs with new molecularly targeted agents. ⋯ There have also been advances in delivery vehicles for platinum drugs (e.g., the diaminocyclohexane [DACH]-based AP-5346 and aroplatin/liposomal cis-bis-neodecanoato-trans-(R,R)-1,2-diaminocyclohexane platinum (II) [L-NDDP] are in early clinical development). Platinum-based drugs have also been successfully combined with molecularly targeted drugs (e.g., the recent approval of the vascular endothelial growth factor monoclonal antibody bevacizumab with carboplatin and paclitaxel in patients with NSCLC).
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Inhaled mannitol has recently been given fast-track status as an investigational drug to treat the lung manifestations of cystic fibrosis. It seems to work in a similar way to nebulized hypertonic saline, osmotically inducing water flux into the bronchial lumen, thereby increasing the hydration of airway mucus, which can then be cleared more effectively by mucociliary clearance and coughing. ⋯ Longer-term studies studying end points of clinical relevance are ongoing. This article assesses its likely future role in cystic fibrosis.