Future oncology
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Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). ⋯ In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
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Improvements in therapies have significantly changed survival of cancer patients. However, the clinical history and oncologic treatment put cancer patients at higher risk for developing cardiovascular problems. ⋯ Recognition of a cardiac impairment during or after a potential cardiotoxic treatment requires a stringent assessment of clinical symptoms and signs of heart failure associated with an evaluation of the left ventricular ejection fraction, which, however, detects the damage already installed. Circulating cardiac biomarkers are promising in detecting cardiotoxicity and will likely change the approach for identifying patients at risk.
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Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action.
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Carfilzomib is a proteasome inhibitor that irreversibly binds to its target, resulting in sustained proteasomal inhibition with minimal off-target effects. As a single agent, carfilzomib has demonstrated durable antimyeloma activity with manageable toxicities, which has resulted in its approval in Argentina, Israel, Mexico and the USA for the treatment of patients with relapsed and refractory multiple myeloma. Data from ongoing Phase III studies that are evaluating carfilzomib in earlier lines of therapy may facilitate an expanded indication for this agent, as well as for regulatory approval in the EU. This article summarizes the chemistry, pharmacokinetics, pharmacodynamics and available clinical data for carfilzomib in the treatment of patients with multiple myeloma.
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EMA licensed eribulin mesylate in 2011 for women with advanced breast cancer already treated with at least two lines of chemotherapy, including anthracyclines and taxanes. Azienda Sanitaria Firenze experience is reported to assess the efficacy and safety of eribulin in the real-life setting. ⋯ Eribulin maintains its activity out of clinical trials, without unexpected toxicities.