Neoadjuvant interferon‐based chemoradiation for borderline resectable and locally advanced pancreas cancer: a Phase II pilot study

Jensen, Eric H.; Armstrong, Leonard; Lee, Chung K.; Tuttle, Todd M.; Vickers, Selwyn M.; Sielaff, Timothy D.; Greeno, Edward

doi:10.1111/hpb.12086

Cited by 17 publications

(14 citation statements)

References 14 publications

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“…Fifty‐six full‐text articles were reviewed, in which 17 studies were excluded due to duplicated studies, no relevant important data, or low research quality and the full‐text versions of two articles could not be obtained. In the end, 39 prospective studies occurring in the time frame of January 2000 to April 2015 were eligible to be included in this review (Fig. ).…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta‐analysis of prospective studies

Zhan

et al. 2017

Cancer Medicine

118

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Section: Resultsmentioning

confidence: 99%

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta‐analysis of prospective studies

Zhan

et al. 2017

Cancer Medicine

118

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“…We conducted these studies using a Syrian hamster model, as these animals are permissive to human adenovirus replication and provide a unique immunocompetent model to objectively analyze the impact of an adenovirus-produced immunostimulatory cytokine [ 23 – 25 ]. With this model, we assessed the use of an OAd expressing hamster IFN in therapeutic protocols similar to the IFN-based therapy used in PDAC clinical trials [ 5 , 7 , 10 ]. We believed that the use of an OAd, which is known to enhance the killing effect of chemotherapy and radiation [ 20 – 22 , 31 – 34 ], in conjunction with a chemo-radio sensitizer such as IFN [ 6 , 7 , 10 ] would greatly improve the effectiveness of chemoradiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, IFN-α (IFN) based therapy regimens have appeared as a promising tool to treat pancreatic cancer. The clinical trials employing neoadjuvant and adjuvant IFN therapies are designed to combine the effectiveness of surgery with chemo-radio sensitization and the immunostimulatory effects of IFN [ 5 – 10 ]. Thus, clinical trials treating PDAC patients with adjuvant IFN-α (IFN) therapy in combination with radiation, 5-FU, and Cisplatin reported 16-36% increases in the 2-year survival [ 7 , 10 , 11 ], and a 35% increase in the 5-year survival [ 9 , 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Combination of interferon-expressing oncolytic adenovirus with chemotherapy and radiation is highly synergistic in hamster model of pancreatic cancer

et al. 2018

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Recent clinical trials utilizing Interferon-alpha (IFN) in combination with chemoradiation have demonstrated significant improvements in the survival of patients with pancreatic cancer. However, efficacy was limited by the systemic toxicity of IFN and low intratumoral levels of the cytokine. We sought to address these drawbacks by using an Oncolytic Adenovirus expressing IFN (OAd-hamIFN) in combination with chemotherapy and/or radiation in regimens mimicking the IFN-based therapies used in clinical trials. IFN expressed from OAd-hamIFN potentiated the cytotoxicity of radiation and chemotherapy (5-FU, Gemcitabine, and Cisplatin), and enhanced pancreatic cancer cell death in both in vitro and in vivo experimental settings. Notably, synergism was demonstrated in therapeutic groups that combined the interferon-expressing oncolytic virus with chemotherapy and radiation. In an in vivo immunocompetent hamster model, treatment regimens combining oncolytic virus therapy with 5-FU and radiation demonstrated significant tumor growth inhibition and enhanced survival. This is the first study to report synergism between an IFN-expressing oncolytic adenovirus and chemoradiation-based therapies. When combined with an IFN-expressing OAd, there is a significant enhancement of radiation and especially chemoradiation, which may broaden the application of this new therapeutic approach to the pancreatic cancer patients who cannot tolerate existing chemotherapy regimens.

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“…It has been demonstrated in vivo that immune checkpoint inhibitors such as antiePD-L1 might enhance the radiation response in PDAC. Using murine pancreatic cancer allografts, the blockade of PD-L1 improved the tumor response to high radiation doses and reduced the development of liver metastasis (105). These data await clinical confirmation (106), and further investigation is ongoing.…”

Section: Targeted Therapy and Immunotherapymentioning

confidence: 84%

Management of Borderline Resectable Pancreatic Cancer

Toesca

Koong

Poultsides³

et al. 2018

International Journal of Radiation Oncology*Biology*Physics

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With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.

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Neoadjuvant interferon‐based chemoradiation for borderline resectable and locally advanced pancreas cancer: a Phase II pilot study

Abstract: Interferon-based neoadjuvant CRT may allow for resection of locally advanced pancreatic cancer, but with significant toxicity. In the absence of surgical resection, survival remains dismal.

Cited by 17 publications

References 14 publications

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta‐analysis of prospective studies

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta‐analysis of prospective studies

Combination of interferon-expressing oncolytic adenovirus with chemotherapy and radiation is highly synergistic in hamster model of pancreatic cancer

Management of Borderline Resectable Pancreatic Cancer

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