Current treatment options in oncology
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Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. ⋯ This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.
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Curr Treat Options Oncol · Jun 2016
ReviewCAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia.
Adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) represents a powerful targeted immunotherapy that has shown great promise in some of the most refractory leukemias. CAR-modified T cells directed against CD19 have led the way, setting a high standard with remission rates as high as 90 % in clinical trials for relapsed/refractory acute lymphoblastic leukemia (ALL). Yet, the first demonstration of efficacy was in another disease, chronic lymphocytic leukemia (CLL), in which CD19-targeted CAR T cells eradicated bulky, highly refractory disease. ⋯ As might be expected with a highly effective therapy using a single mechanism of action, escape pathways have emerged. Combinatorial approaches are needed to anticipate and prevent this mode of relapse. Lastly, toxicity management is vital to ensure the safety of this exciting cancer immunotherapy.
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Curr Treat Options Oncol · Jun 2016
ReviewCheckpoint Inhibitors and Other Immune Therapies for Hodgkin and Non-Hodgkin Lymphoma.
Treatment for relapsed/refractory (R/R) Hodgkin and non-Hodgkin lymphoma remains challenging. The introduction of rituximab to B cell non-Hodgkin lymphoma (B-NHL) treatment significantly improved patients' response rate and survival; however, approximately one third of patients with diffuse large B cell lymphoma, the most common B-NHL subtype, still have a relapse or become refractory after first-line therapy. More recently, antibody therapies and small-molecule inhibitors were approved for treating R/R lymphomas; these agents include brentuximab vedotin, ibrutinib, and idelalisib. ⋯ Formal approval of these drugs is being awaited, as are the results of combination therapy with checkpoint inhibitors and other treatment modalities, including conventional chemotherapy, small-molecule inhibitors, and other immune therapies. Although response rates have been promising, attention must be paid to the management of unique immune-related adverse events, which warrant close monitoring in some cases. Identification of biomarkers that predict response or severe adverse events using either the tumor specimen or peripheral blood would aid in selecting patients suited for these types of treatment as well as determining the ideal sequence of treatment within the realm of immune therapies.
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Curr Treat Options Oncol · Jun 2016
ReviewSABR vs. Limited Resection for Non-small Cell Lung Cancer: Are We Closer to an Answer?
Lobectomy is currently the guideline-recognized gold standard for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) in patients who are surgical candidates. In patients who are not medically fit for surgery, stereotactic ablative radiotherapy (SABR) is the treatment of choice with good reported rates of local control and overall survival. For patients at high risk for lobectomy, sublobar resection (SLR) may achieve similar outcomes as lobectomy, especially for peripheral tumors ≤2 cm. ⋯ Co-existing interstitial lung disease can cause increased treatment-related toxicity in both SABR and surgery. Toxicity is generally well tolerated for SABR and SLR, though treatment-related mortality may be higher in surgery. Ongoing comparative effectiveness research, especially through randomized control trials, is crucial in further delineating the roles of SLR and SABR in the treatment of ES-NSCLC.
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Curr Treat Options Oncol · Apr 2016
ReviewThe Use of EGFR Tyrosine Kinase Inhibitors in EGFR Wild-Type Non-Small-Cell Lung Cancer.
The objective response rate and progression-free survival observed with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with metastatic epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) are modest. The adverse events associated with EGFR TKIs are manageable but they must be considered in the context of the limited efficacy. The development of anti-PD-1 immunotherapy as second-line therapy has reduced the role of EGFR TKIs in EGFR wild-type NSCLC. ⋯ My practice pattern for patients with EGFR wild-type NSCLC is platinum-based chemotherapy as first-line therapy, immunotherapy as second-line therapy, and single-agent chemotherapy as third-line therapy for patients with preserved performance status who want to pursue further therapy. Only a small proportion of patients are eligible for fourth-line therapy, and I prefer to enroll them in clinical trials rather than use EGFR TKIs. I suspect that the use of EGFR TKIs in clinical use and as a comparator arm for clinical trials will continue to decline over the next several years.