Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer

Yang

et al. 2019

Cancers

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

Section: Discussionsupporting

confidence: 89%

Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Yang

et al. 2019

Cancers

“…The decision regarding resectability status of pancreatic cancer should be made by the multidisciplinary meetings consensus following the acquisition of pancreatic imaging including complete staging. In fact, most patients had locally advanced or metastatic disease at diagnosis, and systemic chemotherapy is usually the main treatment (2)(3)(4)(5)(6). Most patients experience relapse after treatment.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Ablation Therapy in Pancreatic Cancer: The Radiologist’s Challenge

Granata

Grassi²,

Fusco

et al. 2020

Front. Oncol.

This article provides an overview of imaging assessment of ablated pancreatic cancer. Only studies reporting radiological assessment on pancreatic ablated cancer were retained. We found 16 clinical studies that satisfied the inclusion criteria. Radiofrequency ablation and irreversible electroporation have become established treatment modalities because of their efficacy, low complication rates, and availability. Microwave Ablation (MWA) has several advantages over radiofrequency ablation (RFA), which may make it more attractive to treat pancreatic cancer. Electrochemotherapy (ECT) is a very interesting emerging technique, characterized by low complication rate and safety profile. According to the literature, the assessment of the effectiveness of ablative therapies is difficult by means of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria that are not suitable to evaluate the treatment response considering that are related to technique used, the timing of reassessment, and the imaging procedure being used to evaluate the efficacy. RFA causes various appearances on imaging in the ablated zone, correlating to the different effects, such as interstitial edema, hemorrhage, carbonization, necrosis, and fibrosis. Irreversible electroporation (IRE) causes the creation of pores within the cell membrane causing cell death. Experimental studies showed that Diffusion Weigthed Imaging (DWI) extracted parameters could be used to detect therapy effects. No data about functional assessment post MWA is available in literature. Morphologic data extracted by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) do not allow to differentiate partial, complete, or incomplete response after ECT conversely to functional parameters, obtained with Position Emission Tomography (PET), MRI, and CT.

“…Modification of the FOLFIRINOX regimen (oxaliplatin 85 mg/m 2 , irinotecan 150 mg/m 2 , 5-FU infusion 2400 mg/m 2 over 46 h, no bolus 5-FU) reduces the incidence of grade 3–4 neutropenia to 47.8% [ 7 ]. More importantly, a meta-analysis showed that the modified FOLFIRINOX regimen is as effective as the original, with a similar tumor response rate (32% versus 33%, p = 0.879), rate of 12-month survival (47% versus 50%, p = 0.38), rate of 6-month PFS rate (47% versus 53%, p = 0.38) and reduced frequency of grade 3–4 adverse events [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy

Yamada

Fujii

Watanabe

et al. 2018

Cancers

While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m2, 2 h bolus injection of L-leucovorin at 200 mg/m2, 90min bolus injection of irinotecan at 150 mg/m2, followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m2 without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.