Current treatment options in oncology
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Curr Treat Options Oncol · Jan 2017
ReviewCheckpoint Inhibitors for the Treatment of Renal Cell Carcinoma.
The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents-but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients. ⋯ Clinically, there are nuances related to the use of immunotherapy that are important to understand in order to provide optimal care to patients. Potential autoimmune toxicities are important to identify early so they can be best mitigated with immunosuppression, and careful review of imaging with clinical correlation is important to ensure responding patients are not taken off treatment prematurely due to "pseudo-progression." Lastly, although immunotherapy is an important new tool, it exists among other active agents in the treatment of RCC, and further study is needed to understand where it best fits in the treatment paradigm. In this article, we review the most recent data for immune checkpoint inhibitors in metastatic renal cell carcinoma and more broadly discuss the rapidly evolving landscape of immunotherapy in RCC, including combination immunotherapies.
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Curr Treat Options Oncol · Jan 2017
ReviewThe Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer.
Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. ⋯ Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib's impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.
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Curr Treat Options Oncol · Nov 2016
ReviewPercutaneous Minimally Invasive Techniques in the Treatment of Spinal Metastases.
Spinal metastases are a common and morbid condition in America. Of the 1.6 million new cases of cancer estimated to be diagnosed in the USA in 2015, approximately 5-10 % will develop spinal metastases. This number is expected to increase as the life expectancy of cancer patients increases. ⋯ Each technique provides its own unique value in the various types of metastatic VCFs encountered, and understanding the uses, advantages, and safety profile of each specific treatment is imperative in providing the best patient care. Percutaneous treatment of metastatic spinal disease is an excellent alternative to medical and surgical management in carefully selected patients. We believe that a multidisciplinary approach and combination therapy allows for optimal pain reduction and improvement of function.
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Curr Treat Options Oncol · Aug 2016
ReviewDeficient Mismatch Repair and the Role of Immunotherapy in Metastatic Colorectal Cancer.
Division of colorectal cancers (CRCs) into molecular subsets yields important consequences for prognosis and therapeutic response. The microsatellite instability (MSI) immune subgroup, accounting for 15 % of early-stage and 3 % of metastatic CRCs, are a result of deficient cellular DNA mismatch repair (dMMR) mechanisms. dMMR CRCs are notable for greater survivability, yet lack of benefit from fluoropyrimidine-based therapy in early-stage disease as compared to proficient DNA mismatch repair (pMMR) CRCs but are substantially lethal when metastatic. ⋯ Next, we will discuss the previous and ongoing clinical trials specifically designed to evaluate immunotherapeutic treatment of dMMR CRCs. Building on the success of the early immune checkpoint inhibitor clinical trials for dMMR CRC, combinations with other anti-tumor immunotherapies may provide an even more robust response, thereby, creating an alternative treatment regimen for those who have failed standard therapies or possibly resulting in prophylactic therapies for patients with highly oncogenic hereditary mismatch repair deficiencies.
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Curr Treat Options Oncol · Aug 2016
ReviewTargeted Therapeutics in Patients With High-Grade Gliomas: Past, Present, and Future.
High-grade gliomas remain incurable despite current therapies, which are plagued by high morbidity and mortality. Molecular categorization of glioma subtypes using mutations in isocitrate dehydrogenase 1/2 (IDH1/2), TP53, and ATRX; codeletion of chromosomes 1p and 19q; DNA methylation; and amplification of genes such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor, alpha polypeptide provides a more accurate prognostication and biologic classification than classical histopathological diagnoses, and a number of molecular markers are being incorporated in the new World Health Organization classification of gliomas. However, despite the improved understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways, these observations have so far failed to result in the successful application of targeted therapies, as has occurred in other solid tumors. ⋯ Mutations in the IDH1/2 genes are central to gliomagenesis in a high proportion of grade II and III gliomas, and ongoing trials are examining vaccines against IDH1, small molecular inhibitors of IDH1 and IDH2, and metabolic components including NAD+ depletion to target IDH-mutated gliomas. The central role of DNA methylation in a subset of gliomas may be targetable, but better understanding of the relation between epigenetic alterations and resulting tumor biology appears necessary. Ultimately, given the prior failure of single-agent targeted therapy in high-grade gliomas, it appears that novel combinatorial therapy or targeted drugs with immunomodulatory or epigenetic approaches will likely be necessary to successfully combat these challenging tumors.