The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

Abstract

Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting. Radiation and chemoradiation have also been incorporated into neoadjuvant strategies, and delivery of alternative fractionation regimens is being explored. This review provides an overview of neoadjuvant therapies for pancreatic cancer. KEYWORDS• 5-fluorouracilPancreatic adenocarcinoma is considered one of the most aggressive malignancies. Most patients are diagnosed with advanced stage disease and only 15-20% of patients are considered candidates for curative resection. An additional 5-10% is diagnosed with borderline resectable or locally advanced disease. Although surgical resection is considered the only potentially curative treatment, resection alone results in low cure rates with median overall survival (OS) rates of approximately 20 months [1,2]. Pancreatic cancer is biologically aggressive and lacks therapeutic agents that are effective against micrometastases. Even in patients who undergo complete surgical resection followed by adjuvant chemotherapy with or without radiation, the risk for systemic recurrence can be as high as 77%, and may be either locoregional or distant in nature [3].Response rates to adjuvant therapies are variable and there is no reliable method to identify which patients will respond to treatment. Nonetheless, some randomized studies demonstrate OS and disease-free survival advantages associated with adjuvant therapies for resectable pancreatic cancer [4,5].Unlike adjuvant therapy, a neoadjuvant treatment approach potentially allows for in vivo assessment of tumor response. In addition, the use of early systemic therapy prior to surgery allows treatment of radiographically undetectable metastatic disease in some patients. It has been reported that 670REviEW Russo, Ammori, Eads & Dorth future science group disease progression occurs in 45-74% following neoadjuvant chemoradiation [6][7][8][9] and 30-78% following neoadjuvant chemotherapy [10] . Noncurative surgery and its associated risks can be avoided in patients who demonstrate disease progression following n eoadjuvant therapy.Neoadjuvant treatment also has the potential to improve compliance [11] as adjuvant therapy is frequently delayed due to recovery from surgery. It is estimated that approximately 25% of patients undergoing curative resection for pancreatic cancer do not receive the planned postoperative treatment due to surgical co...

Expression and prognostic significance of TRPV6 in the development and progression of pancreatic cancer

“…At present, gemcitabine is the first line chemotherapy of pancreatic cancer. There are no randomized data favoring neoadjuvant (including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine) overwhelming adjuvant therapy (27). Docetaxel/ oxaliplatin (DocOx) combination as the second line treatment for advanced pancreatic cancer is an effective option (28).…”

Vascular beds maintain pancreatic tumour explants for ex vivo drug screening

“…To investigate the responses to chemotherapeutic drugs, we cultured PANC-1 tumour explants and VTEs and treated each with gemcitabine (GEM) or abraxane (ABX; Russo, Ammori, Eads, & Dorth, 2016). We also tested PANC-1 cell spheroids, as this is a commonly used model to study tumours in vitro.…”

Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies

“…Interestingly, radiochemotherapy was claimed to be superior to monotherapy treatment by Gillen and colleagues [ 103 ]; however, only marginal benefit of preoperative gemcitabine with or without radiation has been reported in another study. 5-FU based chemoradiation has been widely applied as neoadjuvant treatment for resectable tumours [ 104 ]; anyhow, its efficacy is far from being optimal. It also showed considerable toxicity, with 32% of patients requiring hospitalization in one of the conducted studies [ 92 ].…”