FOLFIRINOX In Pancreatic Cancer Research Articles

Comparative effectiveness of NALIRIFOX vs. FOLFIRINOX in pancreatic cancer.

Comparative effectiveness of NALIRIFOX vs. FOLFIRINOX in pancreatic cancer.

The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer.

Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.

Retrospective Analysis of 2nd-line Nab-Paclitaxel + Gemcitabine After 1st-line FOLFIRINOX in Pancreatic Cancer

Retrospective Analysis of 2nd-line Nab-Paclitaxel + Gemcitabine After 1st-line FOLFIRINOX in Pancreatic Cancer

P-145 - FOLFIRINOX in pancreatic cancer: A careful review

P-145 - FOLFIRINOX in pancreatic cancer: A careful review

46P Identification of novel biomarkers distinguishing pancreatic head cancer from distal cholangiocarcinoma discovered by proteomics analysis

Background Pancreaticcancerandcholangiocarcinomaarethemostaggressivecancer types with dismal prognosis. New combination chemotherapy, such as nab-paclitaxal plus gemcitabine, FOLFIRINOX for pancreatic cancer and cisplatin plus gemcitabine for cholangiocarcinoma, have improved progression-free survival and overall survival in patients with unresectable locally advanced or metastatic cancer. However, it is often difficult to distinguish pancreatic head cancer from distal cholangiocarcinoma, because of their histological and anatomical similarity. This study aims to identify novel protein biomarkers to distinguish these lethal cancers, using proteomic analysis of laser micro- dissected (LMD) formalin-fixed paraffin embedded tissue (FFPE). Methods Ten cases of pancreatic head cancer and 8 of distal cholangiocarcinoma were analyzed. Cancerouscellscollected from FFPE tissuesectionsby LMDwereprocessed for liquid chromatography tandem MS (LC-MS/MS). Candidate proteins were identified by semi-quantitative comparison so-called spectral counting analysis and also chosen based on the nonparametric G-test with statistical significance as indicated by p < 0.01. Results Consequently, 1,361 proteins were detected in pancreatic head cancer and 1,274 proteins in distal cholangiocarcinoma. In total, 1,820 proteins were detected from 18 samples. The detected proteins were semi-quantitatively compared and statistically analyzed by G-test with a significant difference. We identified 6 proteins were overexpressed in pancreatic head cancer groups and 12 proteins in distal cholangiocarcinoma groups, respectively. Conclusions We identified 18 candidate protein biomarkers for distinguishing pancreatic head cancer from distal cholangiocarcinoma using proteomic analysis. Legal entity responsible for the study Tohoku University Funding Japan Society for the Promotion of Science Disclosure All authors have declared no conflicts of interest.

Induction chemotherapy with FOLFIRINOX in pancreatic cancer and then? Experience with a novel scheme of maintenance, treatment pause and re-induction

Introduction: Chemotherapy regimens for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX (5-fluoruracil (5FU/LV), Oxaliplatin, Irinotecan and Leucovorin) which confer a significant survival benefit compared to gemcitabine-based monotherapy. Increased toxicity, mainly sensory peripheral neuropathy, limits its use and the number of applied chemotherapy cycles. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance, treatment pause and re-induction therapy in locally advanced or metastatic PDAC to alleviate such toxicities and increase the number of applied cycles. In this retrospective study we report our experience with this scheme.

FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience.

Background:FOLFIRINOX has been shown to significantly increase both overall survival (OS) and progression-free survival (PFS) in metastatic pancreas cancer. There is limited data regarding the treatment of locally advanced pancreatic cancer. We present a retrospective study of patients with both locally advanced and metastatic pancreas cancer using FOLFIRINOX as first-line therapy in our centre.Methods:This is a retrospective review of patients treated with FOLFIRINOX for pancreatic cancer at Princess Margaret Cancer Centre, between December 2011 and July 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications.Results:One hundred two patients were identified; 66 metastatic and 36 locally advanced. Sixty-eight per cent of patients initiated treatment with a dose reduction. The median (95% CI) OS in the metastatic group was 13.1 (6.3–16.1) months with full dose and 12.9 (10.3–30.1) months with modified dose. The median (95% CI) OS in the locally advanced group was 11.1 (6.1–not reached) months with full dose and 23 (not reached–not reached) months with modified dose. The median (95% CI) PFS in the metastatic group was 6.2 (4.9–15.2) months with full dose and 8.7 (5.7–12.9) months with modified dose. The median (95% CI) PFS in the locally advanced group was 11.1 (3.1–not reached) months with full dose and 10.4 (6.8–not reached) months with modified dose. Grade 3/4 haematologic adverse events were observed in 43% of patients. Grade 3/4 non-haematologic adverse events were observed in 28% of patients. Patient well-being significantly improved from baseline to cycle 4 (P=0.002).Conclusions:Efficacy was achievable with dose-modified FOLFIRINOX in daily setting. The safety of FOLFIRINOX remains a concern with a high rate of grades 3 and 4 neutropaenia despite dose reduction.

P-0118 - Folfirinox in Pancreatic Cancer: the National Cancer Institute of Milan Single Experience

Introduction: FOLFIRINOX regimen is an effective therapeutic option in the treatment of advanced pancreatic cancer in patients with good PS with a significant survival benefit compared to gemcitabine. (Conroy et al., N Engl J Med 2011;364:1817). However, the toxicity profile can be relevant. In this retrospective analysis, we reviewed our experience to assess the feasibility of the regimen.

FOLFIRINOX in pancreatic cancer: Can results be reproduced outside the clinical trial setting?

e15236 Background: 30% of patients with pancreatic cancer in Ireland receive chemotherapy. This increases to 60% in those <65 years. FOLFIRINOX is a preferred regimen for select patients with advan...

Nab-paclitaxel (nab-P) combined with FOLFOX for advanced pancreatic cancer: A phase I study.

4123 Background: The contribution of irinotecan to the efficacy of FOLFIRINOX in pancreatic cancer is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in p...

Eastern Canadian Colorectal Cancer Consensus Conference: Standards of Care for the Treatment of Patients with Rectal, Pancreatic, and Gastrointestinal Stromal Tumours and Pancreatic Neuroendocrine Tumours

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

Washington University experience with FOLFIRINOX in pancreatic cancer.

354 Background: The FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) regimen has recently been shown to be an effective treatment with a significant survival benefit in patients with metastatic pancreatic cancer. Concern for treatment-related toxicity, however, has hampered the adoption of this regimen in clinical practice. A FOLFIRINOX registry was created at our institution to document FOLFIRINOX tolerability and efficacy. Methods: Patients with pancreatic cancer who had received at least one dose of FOLFIRINOX were enrolled in the registry. Demographic information, treatment dosage, adverse events, and efficacy data were obtained. Radiographic response was independently verified by a radiologist. Results: Between January 2010 and August 2011, 29 patients were identified with a median age of 57 (range 37-71). 26 (92.8%) had ECOG performance status of 0-1. FOFIRINOX was given to 16 patients with metastatic disease, 12 with locally advanced disease, and one with borderline resectable disease. 17 (61%) received the first cycle with a dose reduction in either irinotecan and/or 5-FU dosage. UGT1A1*28/*28 homozygous genotype was found in 4 patients who all received dose reduced irinotecan. 13 patients (46%) were started on G-CSF prophylactically with the first cycle while 5 additional patients (18%) had G-CSF support added in later cycles. Main adverse events were neutropenia (grade 3-4 in 14.2%), and abdominal pain and diarrhea (grade 3-4 in 7% and 4% respectively). One incidence of neutropenic fever was observed. Four patients were hospitalized for treatment-related toxicity while three had therapy discontinued due to intolerance. At present, 19 patients have imaging available to determine efficacy: 5 (26%) had partial response, 12 (63%) stable disease, and 2 (11%) had progression of disease as their best response. For patients with locally advanced disease, 11 out of 12 had clinical benefit on FOLFIRINOX. Conclusions: In our practice, FOLFIRINOX was well tolerated and was efficacious, consistent with previously published data. It was frequently used in the setting of locally advanced disease and had similar benefit and tolerability in this setting.