Use Of FOLFIRINOX Research Articles

Neoadjuvant Treatment Approaches for Stage II–III Rectal Cancer

Excellent long-term outcomes are being achieved with contemporary treatment strategies for localized rectal cancer. A “watch-and-wait” nonoperative strategy seems to be a safe option for patients experiencing a complete clinical response. Total neoadjuvant therapy (TNT) has shown many advantages over standard chemoradiotherapy, although the optimal sequencing—with induction or consolidation chemotherapy—is still debated. The use of FOLFIRINOX can boost the benefit of TNT. Of note, in the small subset of patients whose tumors have mismatch repair deficiency, checkpoint inhibition has led to responses in most patients, eliminating the need for further treatment.

Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer.

Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.

Protection of gemcitabine-loaded polylactic-co-glycolic acid microspheres combined with CAR-T treatment against pancreatic ductal adenocarcinoma

Pancreas ductal adenocarcinoma has a highly aggressive phenotype and is one of the most lethal malignancies in the world. Although the use of FOLFIRINOX and abraxane plus gemcitabine chemotherapy regimens have improved patient care, their recurrence rates and long-term survival are still not promising. In this study, PLGA/gemcitabine microspheres were prepared by emulsification–solvent volatilization using gemcitabine as the drug model, and scanning electron microsopy showed that the microspheres had a smooth surface, small size, and large specific surface area. The PLGA microspheres have a high loading capacity and are capable of long-term release. The combination of PLGA/gemcitabine microspheres with chimeric antigen receptor T-cell treatment can regulate MUC1 expression in epithelial cells and reduce the aggressiveness of tumors; thus, it is expected to be applied in the treatment of pancreatic ductal adenocarcinoma.

Study protocol of the HGCSG1803: a phase II multicentre, non-randomised, single-arm, prospective trial of combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) as first-line treatment for metastatic or relapsed pancreatic cancer

IntroductionCombination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has become one of the standard treatments for metastatic pancreatic cancer. However, the use of FOLFIRINOX requires prolonged infusion. Therefore, we...

Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis.

ObjectiveTo undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer.MethodsThis meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken.ResultsThe analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens.ConclusionFOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300

Outcomes in patients receiving palliative chemotherapy for advanced biliary tract cancer

Background & AimsAdvanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors.MethodsFrom January 2010 until December 2019, 142 patients started palliative chemotherapy at our tertiary care liver center. Overall survival (OS) was calculated using Kaplan-Meier plots. Prognostic factors were evaluated using cox proportional-hazards.ResultsPatients received a median number of 2 lines of chemotherapy. Median OS was 6.7, 15.2 and 18.2 months for patients who received 1, 2 and 3 lines of chemotherapy, respectively. Patients treated with FOLFIRINOX had a significantly extended OS of 23.8 months (log-rank test: p = 0.018). The univariate cox regression analysis identified several clinical parameters associated with survival (e.g. albumin, bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 levels).ConclusionsOur study provides real-world data on the prognosis of ABTC including survival times for patients receiving third and later lines of chemotherapy.Lay summaryReal-world data depicting the outcome of patients with advanced biliary tract cancer outside the framework of controlled trials remain rare despite being extremely important for clinical decision-making. This study therefore provides important real-world data on the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX, as well as on other chemotherapy regimens or later lines of chemotherapy. It further demonstrates that the use of FOLFIRINOX is associated with promising survival and that there is an association between various clinical parameters such as pre-therapeutic albumin, bilirubin or carbohydrate antigen 19-9 levels and survival.

Survival and Predictive Factors of Chemotherapy With FOLFIRINOX as First-Line Therapy in Metastatic Pancreatic Cancer: A Retrospective Multicentric Analysis.

The use of FOLFIRINOX (a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) is one of the therapeutic standards in pancreatic adenocarcinoma. We analyzed progression-free survival (PFS) and overall survival (OS) and their predictive factors in patients treated with FOLFIRINOX as first-line therapy in metastatic pancreatic cancer. This multicenter retrospective analysis included patients treated with FOLFIRINOX between 2011 and 2015. The Kaplan-Meier method was used to estimate OS and PFS. The statistical comparison for survival was performed by the log-rank test. Predictive factors were estimated in multivariate analysis with the use of a Cox model. One hundred and thirty-six patients were included (74 men, 62 women; median age, 62 years [range, 29-74 years]). The median PFS was 5.97 months (95% confidence interval, 4.4-6.63 months). The median OS was 8.93 months (95% confidence interval, 7.4-10.07 months). Prognostic factors in multivariate analysis were the use of granulocyte colony-stimulating factor, which appeared to be a good prognostic factor. Dose intensity of oxaliplatin (≥74.48%) and dose intensity of bolus of fluorouracil (>6.9%) appeared as pejorative factors. In patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX in first line, dose modifications at the onset of adverse effects and early use of granulocyte-colony stimulating factor seem to be associated with a better survival.

Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

PurposeThis pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC).Patients and methodsPeripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome.ResultsHeterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively.ConclusionsChemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

CCL26 is upregulated by nab-paclitaxel in pancreatic cancer–associated fibroblasts and promotes PDAC invasiveness through activation of the PI3K/AKT/mTOR pathway

Recently, the combined use of FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel has significantly improved the prognosis of patients with pancreatic cancer. However, there is still a high proportion of patients who develop metastatic pancreatic cancer in the course of chemotherapy or within a short period after chemotherapy. Previous reports have shown that chemotherapy-driven cytokine storms or the direct effects of certain chemotherapeutics on stromal and/or immune cells collectively change the microenvironment of the primary tumor, thus indirectly promoting metastasis. However, the mechanism underlying chemotherapy-induced metastasis in the course of chemotherapy, and afterwards, remains elusive in pancreatic cancer. In the present study, we aimed to determine the expression of CCL26 in the pancreatic cancer-associated fibroblasts (CAFs) after nab-paclitaxel treatment and to explore the role of CCL26 in the pancreatic adenocarcinoma (PDAC) invasion. Our results showed that nab-paclitaxel increased CCL26 mRNA and protein expression levels in a dose- and time-dependent manner. Subsequently, PDAC cell lines were treated with recombinant CCL26 for 48 h. The transwell migration assay showed that recombinant CCL26 enhanced the invasion of PDAC cells. Western blot analysis showed that the protein expression levels of phospho-(p-)PI3K, p-AKT, and p-mTOR were increased by CCL26 in PDAC cells. CCL26 expressions in 95 PDAC tissues and adjacent normal tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. CCL26 was found to be overexpressed in PDAC samples, and upregulated CCL26 expression was significantly associated with advanced perineural invasion, lymph node metastasis, and poor differentiation. In summary, our results showed that nab-paclitaxel increased the expression of CCL26 in CAFs, and CCL26 enhanced the invasive potential of pancreatic cancer cells by activating the PI3K/AKT/mTOR axis. Thus, CCL26 may be a potential prognostic biomarker for pancreatic cancer.

Predictors of Survival among Early Onset Pancreatic Adenocarcinoma Patients A Tertiary Care Center Experience.

To characterize clinical features of early onset pancreatic adenocarcinoma (EOPC) patients and explore prognostic factors affecting their survival. Methods: Retrospective review of 95 patients, 45 years old, who presented to the University of Alabama Hospitals with pancreatic adenocarcinoma from September 1998 to June 2018. Results: Median survival time was 12.9 months for all patients. Obesity, male gender, race, and tumor location were not associated with survival. Smoking at time of diagnosis increased risk of death by three folds (HR 3.05, 95% CI, 1.45 - 6.40). Risk of death decreased by 64% (HR 0.36, 95% CI, 0.16 - 0.78) if patients underwent surgery. Median survival was 119.5 months for stage I, 29.9 months for stage II, 23.23 months for stage III, and 6.3 months for stage IV patients. The survival benefit of chemotherapy was only significant with the use of FOLFIRINOX. Conclusions: Some established prognostic features in typical pancreatic adenocarcinoma patients are not predictive of survival in young patients. Cigarette smoking, a known risk factor for the development of EOPC, is also a significant predictor of survival in this patient population. Efforts to improve prognosis of EOPC include early detection, tobacco control, individualized treatment protocols, and studying the biological behavior.

A Retrospective Review Of Outcomes In Locally Advanced Pancreatic Cancer Patients Treated With Dose-Escalated External Beam Radiation

Previous work has suggested improved clinical outcomes with increasing radiation dose for patients with locally advanced pancreatic cancer (PC), but heterogeneous doses and schedules are used across institutions. To evaluate the utility of more uniform standard versus dose-escalated external beam radiation given after modern chemotherapy, we reviewed the outcomes at a single institution among locally advanced PC patients. We identified patients with inoperable or borderline resectable (BR) PC treated with conventional or hypofractionated radiation since the routine use of FOLFIRINOX and Gemcitabine/Abraxane began at our institution (2014-2020). Patients were excluded if they had metastatic disease or concurrent malignancy. Patients were stratified into high-dose (BED10 >70) and standard-dose (BED10<70) groups. Toxicity was evaluated based on CTCAE v 5.0. Overall survival (OS), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were calculated using the Kaplan-Meier method, and compared using the log-rank test. A total of 42 patients, 21 in each dose group, were identified. Median age was 67, with 43% of female subjects. Twenty-nine (71%) subjects had BR disease. Median follow up was 8.5 months. The most common standard dose regimen was 50.4 Gy in 28 fractions (57%), and the dose escalated regimen was 67.5 Gy in 15 fractions (95%). Five (24%) patients in the standard dose and 15 (71%) patients in the escalated dose groups were treated using MR-guided RT. Seven (33.3%) and 6 (28.5%) patients in the standard- and high- dose groups, respectively, underwent pancreaticoduodenectomy following RT. OS was not significantly different between groups (median 8.3 vs 10.0 months, p = 0.853). FFLP (12.2 vs 12.4 months, p = 0.42) and FFDF (16.4 vs 9.0, p = 0.72) were also not different between dose groups. Regardless of dose, patients that underwent resection after radiation had significantly greater OS (7.6 vs 25.7 months, p = 0.01). Among patients who did not proceed to resection, there was a significant improvement in FFLF (median 4.3 vs. 9.1 months, p = 0.05) in the dose-escalated group, and a non-significant improvement in OS (median 6.4 vs 10.0 months, p = 0.10). Three grade 3 GI toxicities occurred (one directly attributable to RT) in the standard dose group, and no grade ≥3 toxicities occurred in the dose-escalated group. Among a cohort of patients with locally advanced PC, use of a dose-escalated radiation resulted in no improvement in overall clinical outcomes with similar toxicity. In patients that did not receive surgery, there was a clinically significant improvement in FFLF and trend towards improvement in survival suggesting truly unresectable patients may benefit most from dose escalation. Prospective trials are warranted to address the utility of dose-escalation in this setting.

Real-world survival outcomes of using neoadjuvant chemotherapy in pancreatic cancer patients: Findings from the PURPLE clinical registry.

e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p &lt; 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p &lt; 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p &lt; 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p &lt; 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival.Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007–2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use.Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007–2011 to 37% in 2012–2016 (p < .001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007–2011: 12–67%, 2012–2016: 20–54%) whereas overall survival increased from 5.6 months to 6.4 months (p < .001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015–2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015–2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy.Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens.

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: A population-based analysis

Presenter: Anouk Latenstein MD | Amsterdam UMC Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival. Methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007-2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient-, tumor- and hospital characteristics, were used to analyze variation of chemotherapy use. Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007-2011 to 37% in 2012-2016 (P < 0.001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007-2011: 12-67%, 2012-2016: 20-54%, Figure 1). In all patients, overall survival increased slightly from 3.3 months to 3.4 months (P < 0.001) whereas overall survival increased from 5.6 months to 6.4 months (P < 0.001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015-2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015-2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy. Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens.

196P - The tolerability and efficacy of FOLFIRINOX in gastro-oesophageal carcinoma

Background5-FU based regimens represent the gold standard of therapy for gastroesophageal carcinomas. Options include Cisplatin-5FU doublets, FOLFOX and FOLFIRI, and in the neo-adjuvant setting FLOT is emerging as a popular choice for those with good performance status. We identified two cohorts of patients who received m-FOLFIRINOX as first line treatment of gastroesophageal carcinoma; patients undergoing neo-adjuvant therapy in whom FLOT was thought to be too toxic, and those with extensive metastatic disease where it was thought that they would not be fit enough for second line therapy. In these settings there is a theoretical advantage to FOLFIRINOX as it exploits the synergy between Oxaliplatin and Irinotecan; Oxaliplatin forms platinum-DNA adducts and Irinotecan prevents the repair of these adducts impeding the development of platinum resistance. We prospectively evaluated our single institution use of FOLFIRINOX in both neo-adjuvant and advanced treatment of gastro-oesophageal carcinomas. Methods14 patients with oesophageal, gastro-oesophageal junction or stomach carcinoma gave informed consent to treatment with FOLFIRINOX. Five of these patients had extensive metastatic disease at diagnosis. Response to treatment was recorded via combined CT/PET scanning, endoscopy reports, tumour markers and pathology. ResultsAll nine patients being treated neo-adjuvantly displayed a good metabolic response prior to surgical resection. Of note was one patient who received only two cycles, however achieved reduction in his tumour from T3N2 to T2N0, which was then completely resected. For the five patients with extensive disease, all showed complete metabolic responses on PET, after having an average of 10.6 cycles each of FOLFIRINOX treatment. Only one patient relapsed 6 months after completing treatment, who subsequently responded to FOLFIRINOX retreatment, and died 23 months after diagnosis. ConclusionsFOLFIRINOX appears to be highly effective in the treatment of early stage and metastatic gastro-oesophageal adenocarcinomas, as well as showing an excellent pathological response rate which aids surgical resection. This case series suggest that the regimen should be formally trialled, comparing tolerability and efficacy against FLOT. Legal entity responsible for the studySt John Of God Hospital Subiaco. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Neoadjuvant Therapy for Borderline Resectable Pancreatic Ductal Adenocarcinoma (PDA) Involving a High Volume Pancreatic Centre in Ireland

Background: Neoadjuvant (NA) therapy for borderline resectable PDA patients (pts) appear to improve outcome.[1,2] There is limited data with the use of FOLFIRINOX (FX) and Gemcitabine/nab-paclitaxel (GP). Methods: St. Vincent’s University Hospital (SVUH) is a national referral centre for PDA in Ireland. Pts were identified from the pancreatic MDT discussions. Borderline resectability as defined by the NCCN criteria. Primary endpoints were resection rate and median survival (mOS). Results: 93 pts were identified between 1 Jan 2012 and 31 Dec 2015 with median follow-up of 11.40 mos (95% CI 11.51 – 15.10). 50 (53%) were female with a median age of 67 years (range: 43 -78). NA chemotherapy was administered in 76 pts. Majority were treated with FX (24, 32%) and GP (20, 26%). 53/76, 82% pts had sequential radiation; 58% were treated with long course- and 42% with short course-radiation. 34/53, 64% were planned for surgery. Resection rate was 40% (21/53); 53% (16/30) with FX/GP v 22% (5/23) with other regimens, p=0.02. R0 resection rate was 76% (16/21); 88% with FX/GP v 40% other reg, p=0.03. mOS improved with FX/GP 19.87 mos v other reg 13.36 mos, p<0.005; including in those who were resected, 40.86 mos with FX/GP v 22.31 mos with other reg, p=0.02. There is a trend in improved resection rate between those treated with NA FX/GP in SVUH v other centres; 50% v 23% respectively, p=0.06. Conclusion: NA FFX/GNP improve resection, R0 resection and mOS. Treatment in high-volume specialist centre may improve resection outcome.

Modified-FOLFIRINOX combined with deep regional hyperthermia in pancreatic cancer: a retrospective study in Chinese patients

Background: FOLFIRINOX chemotherapy displays significant survival improvements in patients with pancreatic cancer. However, toxicities have hampered enthusiasm for the use of FOLFIRINOX in full dose. In order to increase the tolerability, many researchers focused on the modification of FOLFIRINOX. On the other hand, hyperthermia (HT) has been considered as an effective ancillary treatment for cancer therapy. Up to now, there is no report evaluating combining deep regional hyperthermia (DRHT) with modified-FOLFIRINOX for pancreatic cancer patients.Methods: In this study, we conducted a retrospective review of pancreatic cancer patients treated with the combination of new form modified-FOLFIRINOX and DRHT (BSD2000). Patients underwent chemotherapy that included low-dose irinotecan (70–130 mg/m2), oxaliplatin (65–70 mg/m2) on day 1 and 5-FU (2400 mg/m2 as a 46 h continuous infusion, no bolus) or capecitabine (CAP) (1000 mg/m2 twice daily on days 1–10) or tegafur, gimeracil and oteracil potassium (TS-1) (80–120 mg/d twice daily on days 1–10), 2-week schedule. Generally, DRHT treatment was performed weekly, 45 min for each time during chemotherapy.Results: The patients receiving mFOLFIRINOX as the first line chemotherapy combining with DRHT, obtained an improvement in OS and PFS, 17 months (95% CI 1.97–32.03 months) and 4 months (95% CI 0–8.29 months) respectively. Overall, this combination regimen was safe; 17.6% patients suffered from grade 3/4 toxicities.Conclusions: In conclusion, we conducted a retrospective study combining mFOLFIRINOX and DRHT, which was well tolerated. The efficacy in the treatment of pancreatic cancer was encouraging, but further studies would be required to prove its merit, compared with conventional treatment.

Neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDA) involving a high volume pancreatic centre in Ireland

Background: Neoadjuvant (NA) therapy for borderline resectable PDA patients (pts) appear to improve outcome [1, 2]. There is limited data with the use of FOLFIRINOX (FX) and Gemcitabine/nab-paclitaxel (GP). Methods: St. Vincent’s University Hospital (SVUH) is a national referral centre for PDA in Ireland. Pts were identified from the pancreatic MDT discussions. Borderline resectability as defined by the NCCN criteria. Primary endpoints were resection rate and median survival (mOS). Results: 93 pts were identified between 1 Jan 2012 and 31 Dec 2015 with median follow-up of 11.40 mos (95% CI 11.51 – 15.10). 50 (53%) were female with a median age of 67 years (range: 43 -78). NA chemotherapy was administered in 76 pts. Majority were treated with FX (24, 32%) and GP (20, 26%). 53/76, 82% pts had sequential radiation; 58% were treated with long course- and 42% with short course-radiation. 34/53, 64% were planned for surgery. Resection rate was 40% (21/53); 53% (16/30) with FX/GP v 22% (5/23) with other regimens, p=0.02. R0 resection rate was 76% (16/21); 88% with FX/GP v 40% other reg, p=0.03. mOS improved with FX/GP 19.87 mos v other reg 13.36 mos, p<0.005; including in those who were resected, 40.86 mos with FX/GP v 22.31 mos with other reg, p=0.02. There is a trend in improved resection rate between those treated with NA FX/GP in SVUH v other centres; 50% v 23% respectively, p=0.06. Conclusion: NA FFX/GNP improve resection, R0 resection and mOS. Treatment in high-volume specialist centre may improve resection outcome.

Chemoradiation after FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer.

The safety and efficacy of FOLFIRINOX (FX) followed by consolidative chemoradiation (CRT) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has not been extensively studied. We sought to evaluate outcomes and toxicities of this regimen. A retrospective review was performed of 33 patients with BRPC or LAPC treated with FX followed by CRT. Radiotherapy was directed at the primary tumor and any involved nodes (84.8% received 50-50.4 Gy with standard fractionation and concurrent capecitabine, while 15.2% of patients received 36 Gy in 15 fractions with weekly gemcitabine). Toxicities of FX and CRT were graded using Common Terminology Criteria for Adverse Events (CTCAE v4.0), and radiographic response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS), distant metastasis-free survival (DMFS), and local control (LC) were calculated using Kaplan-Meier analyses, and a Cox proportional hazards model was used to assess the impact of clinicopathologic factors on OS. Median follow-up was 19.9 months and patients received a median of 6.4 months of chemotherapy (range, 2.2-12.0 months). There were more T4 tumors than T3 tumors (70% vs. 30%). Grade ≥3 toxicities were low, including fatigue (9.1%), diarrhea (6.1%), neuropathy (6.1%), and dehydration (6.1%). R0 surgical resection was achieved in 5 patients (15.2%) after CRT. Median OS was 22.0 months (91% at 1 year and 45% at 2 years). Median DMFS was 17.8 months (69% at 1 year and 35% at 2 years). LC was 84% at 1 year and 55% at 2 years. OS is promising with the use of FX in BRPC and LAPC, and consolidative CRT was well tolerated in this cohort. Therefore, the role of radiation after multi-agent chemotherapy should be further evaluated in prospective trials.

Uptake and Effectiveness of FOLFIRINOX for Advanced Pancreatic Cancer: a Population-based Study

AimsAlthough FOLFIRINOX is a standard treatment option for advanced pancreas cancer, there are few data describing utilisation and effectiveness in routine clinical practice. Here we report practice patterns and outcomes in the general population of Ontario, Canada. Materials and methodsUsing the Ontario Cancer Registry and New Drug Funding Program, we identified all patients with pancreas cancer treated with palliative intent gemcitabine or FOLFIRINOX in Ontario during 2006–2014. FOLFIRINOX became available in Ontario's single-payer health system in November 2011. Gemcitabine cases were classified as pre-FOLFIRINOX era (2006–2010) or post-FOLFIRINOX era (2011–2014). Cases treated with perioperative chemotherapy were excluded. Comparisons of proportions between study groups were made using the chi-square test. Overall survival was measured from the date of chemotherapy initiation. ResultsDuring 2006–2014, 3826 patients in Ontario were treated with gemcitabine (n = 3042) or FOLFIRINOX (n = 784) chemotherapy for advanced pancreas cancer. Uptake of FOLFIRINOX increased from 41% (206/505) of treated cases in 2012 to 56% (274/486) of treated cases in 2014. The median overall survival of patients treated with gemcitabine was 5.0 months in 2006–2010 and 4.8 months in 2011–2014. The median overall survival of FOLFIRINOX patients treated in 2011–2014 was 8.2 months. ConclusionThe use of FOLFIRINOX in the general population has increased since 2011. Survival outcomes show a substantial efficacy–effectiveness gap between the pivotal Prodige 4/ACCORD 11 clinical trial and routine practice.