NeoGemTax: Gemcitabine and Docetaxel as Neoadjuvant Treatment for Locally Advanced Nonmetastasized Pancreatic Cancer

Sahora, Klaus; Kuehrer, Irene; Schindl, Martin; Koelblinger, Claus; Goetzinger, Peter; Gnant, Michael

doi:10.1007/s00268-011-1113-8

Cited by 49 publications

(32 citation statements)

References 49 publications

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“…Recent meta-analyses have provided evidence of BRPC and LAPC being advantageous over neoadjuvant strategies (30): i) Neoadjuvant treatment may avoid handicapping postoperative surgical complications (31); ii) neoadjuvant treatment may assist in avoiding unnecessary major abdominal surgery during treatment; iii) chemotherapeutic agents have an improved effect owing to increased vascularization and subsequent drug delivery to neoplastic tissues without surgical trauma (32); iv) for BRPC and LAPC patients, neoadjuvant therapy leads to down-staging of the disease and increasing the rate of R0 resections (26,33-39); v) a number of studies identified a decreased incidence of anastomotic fistulas following neoadjuvant treatment (40)(41)(42)(43); and xi) analyses of the costs of various treatments for pancreatic cancer identified an economic advantage for neoadjuvant treatment regimens (40,44). As the most significant factor predicting long-term survival in pancreatic cancer patients is an R0 resection, the most important factor of neoadjuvant treatment for LAPC and BRPC patients is increasing the rate of R0 resections.…”

Section: Neoadjuvant Treatmentmentioning

confidence: 99%

Neoadjuvant chemotherapy for pancreatic cancer: Effects on cancer tissue and novel perspectives

et al. 2017

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Abstract. Chemotherapy for pancreatic cancer has diversified following the addition of more treatment regimens; however, in spite of this, pancreatic cancer remains a fatal disease. Preoperative (neoadjuvant) chemotherapy (NAC) or neoadjuvant chemoradiation therapy (NACRT) has been developed and implemented. For patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), a number of clinical trials have been conducted; NACRT was demonstrated to improve resectability, R0 resection rate, overall survival rate, disease-free survival rate and even an LAPC and BRPC survival advantage over NAC. However, from the knowledge obtained from resected specimens following preoperative treatment, residual pancreatic cancer tissues following NAC are rich in chemoresistant cancer stem-like cells and epithelial-mesenchymal transition (EMT) markers. Conversely, metformin, angiotensin receptor blocker, statins and low-dose paclitaxel are well-known as drugs that inhibit EMT, which is associated with cancer stem cell-like characteristics. Although clinical effectiveness is unlikely to be achieved using one of these as an anticancer agent, it is reasonable to use these drugs for patients with comorbidities in the treatment of pancreatic cancer. Furthermore, gemcitabine (GEM) affects antitumor immunity by stimulating the expression of major histocompatibility complex class I-related chain A on the surface of cancer cells to enhance the cytotoxicity of natural killer cells. Considering EMT and antitumor immunity, there is a possibility that GEM and nanoparticle albumin-bound paclitaxel therapy is the most suitable regimen for treating pancreatic cancer. However, even as preoperative treatment progresses, R0 resection is the most important factor for the long-term survival of pancreatic cancer patients.

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Section: Neoadjuvant Treatmentmentioning

confidence: 99%

Neoadjuvant chemotherapy for pancreatic cancer: Effects on cancer tissue and novel perspectives

et al. 2017

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“…Data from prospective trials containing patients with borderline resectable disease demonstrate that the surgical resection rate ranges from 24 to 64%, and the R0 resection rate ranges from 87 to 100% [56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Although most of these studies are small, neoadjuvant chemoradiation appears to be associated with good potential for downstaging and R0 resection in this population, which may be in part due to careful patient selection with adequate staging studies, and strict adherence to the definition of borderline resectable.…”

Section: • Neoadjuvant Chemoradiation For Borderline Resectable Diseasementioning

confidence: 99%

“…Neoadjuvant therapy with the intent of sterilizing the margin could be considered in patients with vascular involvement, with particular attention to restaging to tailor surgical recommendations. Several studies suggest that neoadjuvant chemoradiation may enhance margin-negative resectability rates and improve local control [37,[56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Unfortunately, many of the studies are confounded by inclusion of patients with locally advanced unresectable tumors and lack of strict definition of borderline resectable disease.…”

Section: Borderline Resectable Diseasementioning

confidence: 99%

“…The gemcitabine and oxaliplatin as neoadjuvant therapy for locally advanced, nonmetastatic pancreatic cancer trial (NeoGemTax) treated a similar population of 12 borderline resectable and 13 unresectable patients and a similar 32% resection rate was observed. The R0 resection rate was 87% and a median OS of 16 months was observed for those who underwent resection compared with 12 months for those who did not [75]. Despite a lack of radiation and inclusion of patients with locally advanced unresectable disease in these trials, the overall resection and R0 resection rates were high, indicating that chemotherapy alone has a role in the n eoadjuvant setting.…”

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confidence: 98%

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The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

et al. 2016

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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...

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“…After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % and the 1-year overall survival was 100 %. Table 2 shows results of some key studies of neoadjuvant strategy in patients with pancreatic cancer [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. The pragmatic trial from the Intergroup would throw light on how to manage these patients optimally-all patients with borderline resectable pancreatic cancer receive FOLFIRINOX for 4 cycles followed by chemoradiotherapy with capecitabine and if stable or responding, patients are taken for surgery 6-8 weeks post-completion of radiotherapy.…”

Section: Neoadjuvant Therapymentioning

confidence: 99%