Neoadjuvant FOLFIRINOX for Borderline Resectable Pancreas Cancer: A New Treatment Paradigm?

Christians, Kathleen K.; Tsai, Susan; Mahmoud, Anna; Ritch, Paul S.; Thomas, James P.; Wiebe, Lauren Allison; Kelly, Tracy; Erickson, Beth; Wang, Huamin; Evans, Douglas B.; George, Ben

doi:10.1634/theoncologist.2013-0273

Cited by 182 publications

(110 citation statements)

References 11 publications

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“…Beyond the standard cancer treatment options, chemotherapy and radiation, there has been minimal progress made in improving PaCa patient survival. One of the latest attempts is the development of FOLFIRINOX, a combination of five chemotherapeutic agents, which has shown some progress but is associated with toxic side effects if not managed properly [3][4][5][6][7][8]. With the need to develop more effective treatment options, alternative approaches, such as thermal therapy, may offer a viable strategy [9].…”

Section: Introductionmentioning

confidence: 99%

Dual thermal ablation of pancreatic cancer cells as an improved combinatorial treatment strategy

Baumann¹,

Baust²,

Snyder³

et al. 2017

Liver Pancreat Sci

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Pancreatic cancer (PaCa) is one of the leading causes of cancer related deaths in the world today. It is estimated that 95% of patients diagnosed with PaCa will die because of limited treatment options. As standard treatments have not yielded an improvement in patient outcome, alternative approaches, such as thermal ablation, may offer a new treatment path. We previously reported the lethal temperatures necessary for PaCa ablation for both freeze and heat based treatments. In this study, we investigated the response of PaCa cells in vitro to a combination treatment of heating and freezing, dual thermal ablation (DTA), in an effort to further improve ablation efficacy.PaCa cell lines, PANC-1 and BxPC-3, were subjected to heating (45 to 50°C), freezing (-10 to -20°C), or DTA exposure. Post-exposure viability was assessed over a 7-day recovery interval. Modes of cell death were analyzed using fluorescence microscopy and flow cytometry.Our results indicated that in comparison to single thermal modalities, DTA resulted in greater cell destruction at a more rapid rate. Specifically, -15°C had a moderate impact on day one cell viability (PANC-1=80%; BxPC-3=21%) and 50°C (PANC-1=74%; BxPC-3=18%) caused a slow decline in cell number post-treatment. The combination of these treatments resulted in an increased cell death one-day post-treatment (PANC-1=28%; BxPC-3=5%) and achieved complete cell destruction within three days. Overall, these data suggest that a combination of heat and freeze ablation, DTA, may provide for an improved treatment strategy for PaCa.

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Section: Introductionmentioning

confidence: 99%

Dual thermal ablation of pancreatic cancer cells as an improved combinatorial treatment strategy

Baumann¹,

Baust²,

Snyder³

et al. 2017

Liver Pancreat Sci

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“…In the other hand, FOLFIRINOX has been studied as neoadjuvant option for locally advanced and borderline resectable patients [63][64][65] . The neoadjuvant therapy can benefit by converting a few locally advanced tumors into resectable ones and increase R0 resectability in borderline tumors [66,67] .…”

Section: Folfirinox Regimen -Fluorouracil Leucovorin Irinotecan Andmentioning

confidence: 99%

Pancreatic cancer: treatment approaches and trends

Pereira¹,

Corrêa²

2018

JCMT

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Pancreatic cancer is one of the most challenging diseases due to its often late diagnose which results in limited therapeutic options and poor prognosis. To date, the only curative treatment is complete tumor removal surgery but only a few patients are eligible to do it. The median survival period after surgery followed by chemotherapy adjuvant treatment is about 2 years. Since its approval by the FDA, Gemcitabine has become the first-line chemotherapy agent for treatment of advanced pancreatic cancer. The FOLFIRINOX regimen is also used as a treatment scheme for pancreatic cancer; however, this regimen has resulted in small improvements in overall patient's survival. It is appropriated to clarify that the FOLFIRINOX regimen can only be administered in patients with good performance status. Due to the absence of outstanding result after patient's treatment with diverse chemotherapeutic agents combinations or unsuccessful administration of single-agent drugs to treat pancreatic cancer, the immunotherapy has become a new hope. A more comprehensive understanding of cancer microenvironment and the chemical communication between cancer cells and immune cells can result in new therapeutic approaches that will improve the elimination of pancreatic cancer cells, enhancing life quality for these patients and increasing the overall survival.

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“…On the basis of the results of this Actions Concertées dans les Cancers Colo-Rectaux et Digestifs (ACCORD) trial, neoadjuvant therapy with FOLFIRINOX is currently available and leads to the most consistent results for the treatment of metastatic pancreatic cancer and LAPC (45). There are a number of retrospective studies of NAC using FOLFIRINOX for LAPC and BRPC (34,(46)(47)(48)(49). Hosein et al (34) performed a retrospective study of NAC using FOLFIRINOX for LAPC with a 62.5% R0 resection rate, 83% 1-year PFS rate and 100% 1-year OS rate.…”

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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Neoadjuvant FOLFIRINOX for Borderline Resectable Pancreas Cancer: A New Treatment Paradigm?

Cited by 182 publications

References 11 publications

Dual thermal ablation of pancreatic cancer cells as an improved combinatorial treatment strategy

Dual thermal ablation of pancreatic cancer cells as an improved combinatorial treatment strategy

Pancreatic cancer: treatment approaches and trends

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

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