Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer

Tran, Nguyen H.; Sahai, Vaibhav; Griffith, Kent A.; Nathan, Hari; Kaza, Ravi K.; Cuneo, Kyle C.; Shi, Jiaqi; Kim, Edward; Sonnenday, Christopher J.; Cho, Clifford S.; Lawrence, Theodore S.; Zalupski, Mark M.

doi:10.1016/j.ijrobp.2019.08.057

Cited by 31 publications

(32 citation statements)

References 37 publications

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“…Murphy and colleagues report the potential benefit of neoadjuvant fluorouracil, leucovorin, oxaliplatin, and, irinotecan (FOLFIRINOX) and losartan followed by surgical resection in a phase II clinical trial. Of the 49 enrolled patients, 42 underwent attempted surgery and an R0 (margin-negative) resection was achieved in 69% (CI 55%-82%) (25). With neoadjuvant therapy, overall median progression-free survival increases to 17.5 months and overall survival to 31.4 months, although control outcomes were not given (24).…”

Section: Diagnosis Of Pancreatic Adenocarcinomamentioning

confidence: 99%

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

et al. 2020

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This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next discuss current treatment paradigms for pancreatic cancer and the shortcomings of targeted therapy in this disease. Targeting major driver mutations in pancreatic cancer, such as dysregulation in the KRAS and TGF-β signaling pathways, have failed to improve survival outcomes compared to non-targeted chemotherapy; thus, we describe new advances in therapy such as Ras binding pocket inhibitors. We then review next-generation approaches in nanomedicine and drug delivery, focusing on preclinical advancements in novel optical probes, antibodies, small molecule agents, and nucleic acids to improve surgical outcomes in resectable disease, augment current therapies, expand druggable targets, and minimize morbidity. We conclude by summarizing progress in current research, identifying areas for future exploration in drug development and nanotechnology, and discussing future prospects for management of this disease. Clinical Snapshot of Pancreatic AdenocarcinomaPancreatic cancer is the most lethal common tumor in America. The five-year survival is estimated to be 9.3% among all cases and 2.9% among patients with metastatic disease, both lowest amongst all common tumors (1). With its rising incidence and unabated mortality, pancreatic cancer is the third leading cause of cancer related death, with a projection that it will the second by 2030 (Figure 1) (2,3). In 2019, pancreatic ductal adenocarcinoma (PDAC; 95% of patients) represented 3.2% of all new cancer cases, with an estimated 56,770 new cases and 45,750 deaths (7.5% of all cancer deaths) (1).

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Section: Diagnosis Of Pancreatic Adenocarcinomamentioning

confidence: 99%

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

et al. 2020

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“…On the other hand, effective chemotherapy may lead to more adverse events. There is a report that NAT with FFX followed by IMRT concurrent with fixed-dose-rate GEM in BR-PDAC is feasible and tolerated [ 18 ]. Therefore, the IMRT technique may enable the application of NACRT in combination with more effective chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer

Kimura

Yamada

Takami

et al. 2020

Cancers

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Background: The objective of this study was to investigate the optimal neoadjuvant therapy (NAT) for borderline resectable pancreatic cancer invading the portal vein (BR-PV) or abutting major arteries (BR-A). Methods: We retrospectively analyzed 88 patients with BR-PV and 111 patients with BR-A. Results: In BR-PV patients who underwent upfront surgery (n = 46)/NAT (n = 42), survival was significantly better in the NAT group (3-year overall survival (OS): 5.8%/35.5%, p = 0.004). In BR-A patients who underwent upfront surgery (n = 48)/NAT (n = 63), survival was also significantly better in the NAT group (3-year OS:15.5%/41.7%, p < 0.001). The prognosis tended to be better in patients who received newer chemotherapeutic regimens, such as FOLFIRINOX and gemcitabine with nab-paclitaxel. In 36 BR-PV patients who underwent surgery after NAT, univariate analysis revealed that normalization of tumor marker (TM) levels (p = 0.028) and preoperative high prognostic nutritional index (PNI) (p = 0.022) were significantly associated with a favorable prognosis. In 39 BR-A patients who underwent surgery after NAT, multivariate analysis revealed that preoperative PNI > 42.5 was an independent prognostic factor (HR: 0.15, p = 0.014). Conclusions: NAT using newer chemotherapy is essential for improving the prognosis of BR pancreatic cancer. These findings suggest that prognosis may be prolonged by maintaining good nutritional status during preoperative treatment.

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“…Twelve studies reported outcomes for BRPC patients specifically. [22][23][24][25][26][27][28][29][30][31][32][33] Three studies also or solely reported outcomes for patients with resectable pancreatic cancer. [34][35][36] In total, the FOLFIRINOX alone studies included 310 patients (88.3%) with BRPC and 41 patients (11.7%) with resectable pancreatic cancer, whereas all 161 patients (100.0%) in the FOLFIRINOX with radiotherapy studies had BRPC.…”

Section: Included Studiesmentioning

confidence: 99%

Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

et al. 2021

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Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

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Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer

Cited by 31 publications

References 37 publications

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease

Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer

Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

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