FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study

Suker, Mustafa; Nuyttens, J.; Koerkamp, Bas Groot; Eskens, Ferry A.L.M.; Eijck, Casper H.J. van

doi:10.1002/jso.25233

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…Late clinical presentation, early metastasis, and recurrence are mainly responsible for poor prognosis 2 . Currently, the primary therapeutic approaches are curative resection, adjuvant chemotherapy, and radiotherapy 3, 4, 5, 6. Despite extensive research and development efforts aimed at enhancing the clinical management of PDAC, the outcomes remain unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma

Guo

Fesler

Huang

et al. 2020

Molecular Therapy - Nucleic Acids

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Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. There is an urgent need to develop novel strategies to enhance survival and improve patient prognosis. MicroRNAs (miRNAs) play critical roles as oncogenes or tumor suppressors in the regulation of cancer development and progression. In this study, we demonstrate that low expression of miR-15a is associated with poor prognosis of PDAC patients. miR-15a expression is reduced in PDAC while closely related miR-16 expression remains relatively unchanged. miR-15a suppresses several important targets such as Wee1, Chk1, Yap-1, and BMI-1, causing cell cycle arrest and inhibiting cell proliferation. Ectopic expression of miR-15a sensitizes PDAC cells to gemcitabine reducing the half maximal inhibitory concentration (IC50) more than 6.5-fold. To investigate the therapeutic potential of miR-15a, we used a modified miR-15a (5-FU-miR-15a) with uracil (U) residues in the guide strand replaced with 5-fluorouracil (5-FU). We demonstrated enhanced inhibition of PDAC cell proliferation by 5-FU-miR-15a compared to native miR-15a. In vivo we showed the therapeutic power of 5-FU-miR-15a alone or in combination with gemcitabine with near complete elimination of PDAC lung metastatic tumor growth. These results support the future development of 5-FU-miR-15a as a novel therapeutic agent as well as a prognostic biomarker in the clinical management of PDAC.

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Section: Introductionmentioning

confidence: 99%

Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma

Guo

Fesler

Huang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…In recent years, a more efficient but also more toxic systemic therapy regimen consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has been used in patients with LAPC [3]. This novel systemic treatment has renewed interest in chemo-radiotherapy for LAPC, with several single center and multicenter studies reported in the last two years [4], [5].…”

Section: Introductionmentioning

confidence: 99%

The role of biological dose-escalation for pancreatic cancer

Bruynzeel

Lagerwaard

2019

Clinical and Translational Radiation Oncology

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The role of chemo-radiotherapy for treatment of locally advanced pancreatic cancer (LAPC) has been discussed for many years, and the absence of an overall survival benefit compared to gemcitabine chemotherapy alone in the recent LAP07 study seems to have increased the controversy. However, even in this study, chemo-radiotherapy resulted in decreased local progression (p = 0.03). In combination with increased efficacy of novel systemic therapy consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX), radiation dose-escalation may show to be beneficial in LAPC. Stereotactic body radiation therapy (SBRT) can be expected to be the most suitable approach to perform local radiation doseescalation, and has been shown to be both effective and tolerable at doses of 25-35 Gy in 3-5 fractions. Whether further dose-escalation for LAPC will be both feasible and useful is debatable, because of dose restrictions to adjacent critical organs at risk, and the observation that thus far a benefit of delivering BED 10 in excess of 70 Gy has not shown to improve local control significantly. If an attempt to further dose-escalate is performed, stereotactic MR-guided adaptive radiation therapy (SMART) theoretically has the highest potential. In addition to superior soft-tissue setup without the need for implanted fiducial markers and online MR-guidance during delivery with minimal safety margins, daily plan adaptation directed at avoiding undue high doses to critical organs such as the duodenum, stomach and bowel are advantages of this technique over current SBRT. This paper aims to illustrate the SMART technique, which has been delivered in 300 fractions for LAPC or locally recurrent pancreatic cancer at Amsterdam UMC since early 2016.

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“…Several studies demonstrated how FFN as NACT before surgery could be a manageable treatment option with high rate of R0 resection with [28] or without radiotherapy [29,30]. Opposite to those, the studies by Barenboim [31] and Suker [32] registered a low resection rate, which do not support the use of FFN to convert primary non-resectable cancer to resectable. Therefore, the resection rates can profoundly vary, from a 23.4% in the Lee [33] analysis with 64 patients evaluated, to a 44% in the Blazer [34] study where the patients’ population was limited to 25 patients.…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review

Napolitano

Formisano

Giardino

et al. 2019

Cancers

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The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138–0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.

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FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study

Cited by 21 publications

References 30 publications

Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma

Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma

The role of biological dose-escalation for pancreatic cancer

Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review

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