Expert review of anticancer therapy
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Expert Rev Anticancer Ther · May 2014
ReviewPomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data.
Despite the improvements thanks to the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs), nearly all myeloma patients eventually become refractory to these drugs. Consequently, the outcome of these patients is very poor. Pomalidomide is a new IMiD with a similar structure to the commonly used IMiD thalidomide and lenalidomide. ⋯ Based on the results of a Phase III trial, the FDA and EMA agencies granted accelerated approval to pomalidomide, which is now considered a new effective strategy for relapsed and/or refractory myeloma patients. Very promising results were obtained when pomalidomide-dexamethasone was used in combination with other compounds. This review provides updated information about pharmacokinetics, mechanism of action, resistance, clinical efficacy and safety of pomalidomide.
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Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in the regulation of tumor angiogenesis (VEGFR1, 2, 3; angiopoietin-1 receptor), oncogenesis (stem cell growth factor receptor; RET; BRAF including BRAFV600E), and tumor microenvironment (PDGFR-β and FGFR). Based on data from the Phase III CORRECT study, regorafenib stands as a further option for patient affected by metastatic colorectal cancer who have exhausted previous available therapies. Its multi-targeted effect might explain activity in advanced lines of treatment, when cancer cells have been heavily challenged with previous lines of therapy and potentially developed multiple mechanisms of resistance, but also makes difficult to identify predictive biomarkers. In this article we examine preclinical as well as clinical data of regorafenib in the therapy of metastatic colorectal cancer, challenges for potential markers of efficacy and its role in the treatment algorithm.
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Expert Rev Anticancer Ther · Jan 2014
ReviewSequencing therapy in advanced prostate cancer: focus on sipuleucel-T.
Immunotherapies such as sipuleucel-T present new and unique challenges for the optimal timing and sequencing of therapies for metastatic castration-resistant prostate cancer (mCRPC). Key considerations for the sequencing of sipuleucel-T are its unique proposed mechanism of action, the time required to generate a clinically relevant immune response, and the observed efficacy in Phase III trials in 'early' or asymptomatic or minimally symptomatic mCRPC. There are three broad timing and sequencing options for sipuleucel-T in patients with rising prostate-specific antigen and radiologic evidence of disease: immediately after androgen-deprivation therapy failure, after failure of secondary hormonal maneuvers, or after chemotherapy. There are several other agents in Phase III development in mCRPC and any future approvals will impact on the current treatment algorithm, and raise further questions regarding how to optimize sequencing and timing of therapies for better clinical outcomes.
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Despite significant advances in the systemic treatment of metastatic renal cell carcinoma, long-term survival remains low. A potential way to improve outcomes in selected cases is the use of metastasectomy, which is part of the multimodal treatment of this disease. Although the evidence supporting this approach is limited, we believe it is a reasonable option for certain patients. This review summarizes the evidence supporting this approach.
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Expert Rev Anticancer Ther · Nov 2013
ReviewClinical trials of viral therapy for malignant gliomas.
Despite recent scientific advances in the understanding of the biology of malignant gliomas, there has been little change in the overall survival for this devastating disease. New and innovative treatments are under constant investigation. Starting in the 1990s, there was an interest in using viral therapeutics for the treatment of malignant gliomas. ⋯ Multiple Phase I and II trials demonstrated the safety of these techniques, but clinically showed limited efficacy. However, this led to a better understanding of the pitfalls of viral therapy and encouraged the development of new approaches and improved delivery methods. Here we review the prior and ongoing clinical trials of viral therapy for gliomas, and discuss how novel strategies are currently being utilized in clinical trials.