Disease and Therapy of Pancreatic DisorderReviewTherapeutic Advances in Pancreatic Cancer
Section snippets
Resectable Cancer
Pancreatic ductal adenocarcinoma (PDAC) is usually detected at a late stage, when <20% of patients are eligible for potentially curative resection; most of these patients have disease recurrence. Although mortality from PDAC has decreased significantly, particularly among patients treated at high-volume centers, pancreatectomy continues to cause significant morbidities that can affect physicians' ability to deliver adjuvant therapy. It is therefore important to optimize surgical techniques in
Borderline Resectable Pancreatic Cancer
A major development in the clinical management of pancreatic cancer over the last several years has been the recognition of a subset of tumors that cannot be clearly categorized as resectable or locally unresectable. These borderline resectable pancreatic tumors might technically be resectable, but have a high likelihood for positive margins with upfront surgery. A consistent, objective, and standardized definition of borderline resectable pancreatic cancer is required to design and conduct
Locally Advanced and Metastatic Disease
Most patients (80%) present with advanced tumors that cannot be removed by surgery; their management is a significant unmet challenge. More than 50% of patients come to clinical attention with metastatic disease, and an additional 30%–40% present with locally advanced tumors.32, 33 The prognosis for these patients is poor. Patients with locally advanced disease have a median survival time of 8–12 months, and patients with distant metastases have significantly worse outcomes, with a median
Advances in Chemotherapy for Metastatic Disease
The development of improved systemic treatments is a high priority for pancreatic cancer. In 1997, gemcitabine monotherapy was established as standard of care because it was shown to have greater clinical benefit than weekly 5-FU therapy.35 Since then, gemcitabine chemotherapy combinations have been intensely evaluated. Despite frequently encouraging early-phase data, phase III trials of such combinations have yet to demonstrate a statistically significant survival benefit over gemcitabine
Advances in Targeted Therapy
Our increased understanding of the molecular and genetic changes associated with tumorigenesis has led to the development of agents that specifically target these alterations. Targets have included KRAS and downstream factors, such as mitogen-activated protein kinase, epidermal growth factor receptor, vascular endothelial growth factor A, and type I receptor for insulin-like growth factor.60 The characteristically dense stroma and desmoplastic reaction surrounding most pancreatic
Locally Advanced Disease
There are few data from randomized, controlled trials to indicate the best treatment approaches for patients with locally advanced disease. A number of trials have been performed during the past 30 years, often assessing some combination of chemotherapy and radiation. However, it has been difficult to draw conclusions from these studies because of variations in the dose and methods of radiation, use of radiosensitizers, and chemotherapy controls. Combined chemoradiotherapy clearly prolongs
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Conflicts of interest The authors disclose no conflicts.
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Authors share co-senior authorship.