Future oncology
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Review
Optimizing the use of trabectedin for advanced soft tissue sarcoma in daily clinical practice.
Compared with conventional chemotherapy for advanced soft tissue sarcoma, trabectedin has several distinguishing characteristics which, when optimized, may maximize clinical benefits for patients. In this review, evidence is examined with the aim of answering some vital questions about the use of trabectedin in clinical practice. Who should be treated? When should patients be treated? For how long should patients be treated? What is the safety profile of trabectedin? How should trabectedin be administered? In brief, trabectedin has shown activity and clinical benefit in nearly all subtypes of soft tissue sarcoma. ⋯ Trabectedin has a role for treatment of elderly patients in whom alternatives are lacking, and can be administered for prolonged periods without cumulative toxicity. A statistically significant improvement in median progression-free survival has been observed when trabectedin is administered uninterrupted until disease progression. The flexibility of trabectedin administration in terms of dose, interval and duration allows for patient-tailored treatment optimization.
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Multicenter Study
Eribulin in heavily pretreated metastatic breast cancer patients and clinical/biological feature correlations: impact on the practice.
This multicenter study describes the effectiveness of eribulin in current practice. ⋯ Our study confirms the effectiveness of eribulin mesylate in the treatment of patients with metastatic breast cancer and two or more lines of chemotherapy, in particular in the good disease control at the different metastatic sites.
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Randomized Controlled Trial
The HELIOS trial protocol: a phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia.
Ibrutinib is an orally administered, covalent inhibitor of Bruton's tyrosine kinase with activity in B-cell malignancies based on Phase I/II studies. We describe the design and rationale for the Phase III HELIOS trial (trial registration: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745) investigating whether ibrutinib added to bendamustine and rituximab (BR) provides benefits over BR alone in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. ⋯ The primary end point is progression-free survival. Secondary end points include safety, objective response rate, overall survival, rate of minimal residual disease-negative remissions, and patient-reported outcomes. Tumor response will be assessed using the International Workshop on Chronic Lymphocytic Leukemia guidelines.
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Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Nivolumab is approved in Japan and the USA for the treatment of patients with advanced melanoma. A Phase I trial reported overall objective response rates of 17, 32 and 29% in patients with advanced non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively, which included many heavily pretreated patients. 1-/2-year overall survival rates were 42%/24%, 63%/48% and 70%/50% for non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively. ⋯ Nivolumab is associated with a manageable adverse event profile. Numerous clinical trials are investigating nivolumab alone or in combination with other therapies in multiple cancer settings. This article summarizes the development of nivolumab as of November 2014.
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Management of metastatic castration-resistant prostate cancer has changed markedly over the last decade with major shifts in the treatment paradigm, although ultimately still will progress despite currently available therapies. The sequencing or combination of these agents is an area of active investigation, since definitive prospective randomized trials to define the optimal choice of drug sequence have yet to be done or resulted. This article will highlight pivotal trials for currently approved therapies for metastatic castration-resistant prostate cancer and a suggestion for sequencing of these agents, as well as highlighting investigations using novel therapies for advanced prostate cancer.