Alison Marguerite Ivey

Clinical and Radiographic Response With Combined BRAF-Targeted Therapy in Stage 4 Ameloblastoma

Affiliations of authors: Department of Medicine (FJK) and Clinical Trials Office (AMI), University of Florida Cancer Center; Department of Radiology (WD), Department of Radiation Oncology (WMM), and Department of Pathology, Immunology, and Laboratory Medicine (RWA), University of Florida College of Medicine, Gainesville, FL. Correspondence to: Frederic J. Kaye, MD, University of Florida College of Medicine, 2033 Mowry Rd, CGRC Rm 364, Gainesville, FL 32610 (e-mail: fkaye@ufl.edu).

Combination therapy for renal cell cancer: what are possible options?

Antiangiogenic therapy has shown promise in the treatment of patients with renal cell carcinoma (RCC). Two classes of antiangiogenic drugs, the anti-vascular endothelial growth factor antibody bevacizumab and the tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib, have shown efficacy in patients with RCC and are approved by the US Food and Drug Administration for treatment of this cancer. In practice, the clinical benefit of antiangiogenic drugs in RCC has been heterogeneous, and in patients who do respond, benefits are modest and/or short-lived. To improve efficacy, combination targeted therapy has been attempted, but with either very limited additional efficacy or nontolerable toxicities. Recent advances in the molecular understanding of tumor angiogenesis and mechanism of resistance, along with the rapid development of targeted drug discovery, have made it possible to further explore novel combination therapy for RCC.

Multidisciplinary neoadjuvant management for potentially curable pancreatic cancer

Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in the U.S. Despite advances in surgical technique, radiotherapy technologies, and chemotherapeutics, the 5‐year survival rate remains approximately 20% for the 15% of patients who are eligible for surgical resection. The majority of this group suffers metastatic recurrence. However, despite advances in therapies for patients with advanced pancreatic cancer, only surgery has consistently proven to improve long‐term survival. Various combinations of chemotherapy, biologic‐targeted therapy, and radiotherapy have been evaluated in different settings to improve outcomes. In this context, a neoadjuvant (preoperative) treatment strategy offers numerous potential benefits: (1) ensuring delivery of early, systemic therapy, (2) improving selection of patients for surgical therapy with truly localized disease, (3) potential downstaging of the neoplasm facilitating a negative margin resection in patients with locally advanced disease, and (4) providing a superior clinical trial mechanism capable of rapid assessment of the efficacy of novel therapeutics. This article reviews the recent trends in the management of pancreatic adenocarcinoma, with a particular emphasis on a multidisciplinary neoadjuvant approach to treatment.

Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma.

319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m2 bolus and Ox 85 mg/m2 D1; 5-FU 2,400 mg/m2CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w....