Outcomes of Patients with Initially Locally Advanced Pancreatic Adenocarcinoma who did not Benefit from Resection: A Prospective Cohort Study
Jonathan GarnierJacques EwaldUgo MarchèseMarine GilabertSimon LaunayLaurence Moureau-ZabottoFlora PoizatMarc GiovanniniJean‐Robert DelpéroOlivıer Turrini
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Abstract Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR)=1.2, 95% confidence interval: 0.86–1.6, P =.03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR=1.38, 95% confidence interval: 1–1.9, P <.01) and limited short-term treatment-related toxicity. Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.Keywords:
FOLFIRINOX
Induction chemotherapy
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There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity.We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions.Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel.Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).
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Gemcitabine (GEM) has been reported to be an active agent in pancreatic cancer. Single-agent gemcitabine is currently the chemotherapy standard, although response rate being modest. Therefore, studies over the past few years have focused on gemcitabine-based combination chemotherapy and recent applications have included the use of a fixed-dose rate regimen. The purpose of this study is to evaluate the feasibility and efficacy of a new regimen, a fix-dose rate infusion of low-dose GEM (FRI regimen), as compared with a standard infusion (SI regimen) in patients with pancreatic cancer. 27 patients were enrolled (12 patients were resectable and 15 patients were unresectable). This FRI regimen consisted of gemcitabine 300 mg/m2 i.v. 30 minutes once weekly (10 mg/m2/min). Among unresectable patients, partial response was observed each in one patient, while stable disease was seen in four and five patients (FRI versus SI), respectively. A CBR was achieved in three versus two patients. As side effects, grade 3 toxicities were not observed in patients treated with the FRI regimen. The median survival time was 10 months versus 8 months, and this survival difference is not statistical significant. In the adjuvant setting with GEM, 5 of 7 patients treated with the SI regimen discontinued the treatment within 3 cycles because of severe grade 3 or 4 toxicities in spite of dose reduction, while all patients with FRI regimen achieved the entire treatment. The median survival time and disease-free survival time were no significant difference between two groups. In conclusion, the FRI regimen is well tolerated and offers good palliation, as well as the SI regimen, in patients with locally advanced pancreatic cancer. Furthermore, in the adjuvant setting, the FRI regimen resulted in better clinical benefit on quality of life and fewer side effects than the SI regimen.
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Standard treatment for advanced pancreatic cancer has had minimal impact on natural course of the disease. Current standard chemotherapy for healthy, robust patients remains FOLFIRINOX (5fluorouracil, leucovorin, oxaliplatin, and irinotecan) chemotherapy which showed 4-month overall survival benefit compared to gemcitabine alone [2]. Recently MPACT study showed that adding nabpaclitaxel to gemcitabine significantly improved overall survival compared to gemcitabine (8.5 months vs. 6.7 months P=0.000015). However, the combination remains more toxic compared to gemcitabine [3].
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Abstract Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using induction chemotherapy followed by maintenance therapy from 2011 until November 2016 was collected and analyzed retrospectively. Progression free survival was assessed starting induction therapy until progressive disease (PD) during maintenance or treatment pause (PFS1) and until progression during re-induction therapy (PFS2). 13 patients received induction therapy which was followed by maintenance therapy. Re-induction due to PD during therapy was applied in 11 patients. The median PFS1 was 10.6 months (95% CI; 6.7–14.4), PFS2 was 14.1 months (95% CI; 8.2–19.9) and overall survival was 18.3 months (95% CI; 14.8–21.8). The use of FOLFIRINOX as induction, followed by maintenance and re-induction therapy in case of PD is feasible in the treatment of PDAC and might lead to a prolonged PFS with less toxicity.
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Introduction: Despite a clinically relevant, statistically significant survival benefit with nab -paclitaxel plus gemcitabine and FOLFIRINOX vs single-agent gemcitabine for metastatic pancreatic cancer (mPC), little is known regarding their real-world effectiveness. We analyzed patients with mPC using a nationally representative electronic medical records database to address this unmet need. Methods: This retrospective analysis of the Navigating Cancer database compared outcomes among patients who received first-line nab -paclitaxel plus gemcitabine, FOLFIRINOX, or gemcitabine for mPC. Effectiveness, safety, and supportive care use were examined. nab -Paclitaxel plus gemcitabine was the reference for statistical comparisons. Results: Baseline characteristics were similar except age (oldest patients were in the gemcitabine cohort followed by nab -paclitaxel plus gemcitabine, then FOLFIRINOX). Patients receiving nab -paclitaxel plus gemcitabine (n=122) demonstrated similar time to treatment discontinuation (TTD; median, 3.4 vs 3.8 months; P =0.947) and database persistence (DP; median, 8.6 vs 8.6 months; P =0.534) vs FOLFIRINOX (n=80); however, TTD (median, 3.4 vs 2.2 months; P <0.001) and DP (median, 8.6 vs 5.3 months; P =0.030) were significantly longer with nab -paclitaxel plus gemcitabine vs gemcitabine (n=46). There were more any-grade adverse events with FOLFIRINOX or gemcitabine vs nab -paclitaxel plus gemcitabine (95% or 89% vs 84%, respectively). Conclusion: This real-world analysis confirms the phase III MPACT trial findings and demonstrates that nab -paclitaxel plus gemcitabine has effectiveness similar to that of FOLFIRINOX but greater tolerability for treating mPC despite younger patients being in the FOLFIRINOX cohort. These findings support nab -paclitaxel plus gemcitabine as an appropriate first-line treatment option for patients with mPC. Keywords: metastatic pancreatic cancer, nab -paclitaxel, gemcitabine, FOLFIRINOX, comparative effectiveness
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The present study aimed to evaluate the clinical benefits of leucovorin, 5‑fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) vs. gemcitabine plus Nab‑paclitaxel (GnP) as a first‑line therapy for patients with inoperable pancreatic cancer. For this purpose, in‑house data available for 45 patients who received FOLFIRINOX or GnP as first‑line treatment between 2014 and 2019 were retrospectively analyzed. In total, 21 and 24 patients received FOLFIRINOX and GnP, respectively. Although there were no significant differences in the median progression‑free survival, the median overall survival was longer in the FOLFIRINOX group than in the GnP group (16.7 vs. 7.2 months). A total of 14 patients received FOLFIRINOX followed by GnP, whereas 3 patients received GnP followed by FOLFIRINOX. All patients who did not switch to second‑line therapy owing to poor feasibility were included in the GnP group. The data indicated that patients receiving GnP as first‑line therapy were less likely to switch to FOLFIRINOX and, consequently, had a worse prognosis.
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e15796 Background: FOLFIRINOX is well known to be a highly effective treatment in pancreatic cancer for young patients with good performance status. As the original ACCORD study was carried out with patient’s performance status 0 or 1, many oncologists feel uncertain administering modified dose FOLFIRINOX (m-FOLFIRINOX) as a second-line therapy. We have previously reported our experience in 35 patients (aged 27 – 85) where we concluded that m-FOLFIRINOX can be administered safely with appropriate dose reductions. More recently, the systematic review and meta-analysis by Tong et al. concluded that m-FOLFIRINOX is a good choice of therapy even for those with poor performance status. This retrospective analysis assessed the efficacy of m-FOLFIRINOX in second-line treatment of pancreatic adenocarcinoma. Methods: Using an electronic database, patients with either locally advanced or metastatic pancreatic adenocarcinoma were identified who had received first-line gemcitabine plus nab-paclitaxel, followed by second-line m-FOLFIRINOX between January 2013 and July 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Fifty-two patients were identified, with 65% of the patients having metastatic pancreatic disease. Median age of patients was 75 (range, 27 – 86). Dose intensity of m-FOLFIRINOX was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-fluorouracil (5-FU) and 68% for infusional 5-FU. From diagnosis, the median OS of all patients was 45.0 months (95% CI, 25.0 – 63.0). The median OS of the locally advanced and metastatic pancreatic adenocarcinoma was 63.0 months (95% CI, 45.0 – 70.0) and 22.5 months (95% CI, 18.0, 38.0), respectively. Conclusions: Our study demonstrates the safety and efficacy of m-FOLFIRINOX as a second-line therapy after gemcitabine plus nab-paclitaxel failure. These findings correlate with the findings of Tong et al.’s findings of the benefits of m-FOLFIRINOX for advanced pancreatic cancer in patients with poor performance status.
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Background: Pancreatic cancer is a highly aggressive cancer. According to the latest data published by the World Health Organization, the number of new cases in 2020 in Iraq was 674 and represented 2% of all new cancer cases. Most of the pancreatic adenocarcinomas have spread outside the pancreas at the time of diagnosis. Progression free survival is the time between the date of diagnosis to disease progression or death. The current study aims to compare progression free survival between three chemotherapy regimens; Gemcitabine, Gemcitabine/Nab-paclitaxel and FOLFIRINOX of advanced and metastatic pancreatic cancer in Iraqi patients. Methods: Patients were divided into three groups; patients who will receive Gemcitabine, those who will receive Gemcitabine/Nab-paclitaxel, and patients who will receive FOLFIRINOX. The patients were observed for disease progression by computed tomography which was performed every three months for the tumor response and progression. Results: In the Gemcitabine, Gemcitabine/Nab-paclitaxel, and FOLFIRINOX groups, the median Progression Free Survivals were (4, 5, and 5.7 months, respectively; p is less than 0.05), where FOLFIRINOX was superior to Gemcitabine monotherapy and Gemcitabine/Nab-paclitaxel. In addition, neutropenia, febrile neutropenia, diarrhoea, nausea, vomiting, fatigue, hypokalaemia and neuropathy were highly in the FOLFIRINOX-treated patients than in both Gemcitabine and Gemcitabine/Nab-paclitaxel groups of patients. However, anaemia and thrombocytopenia were higher with Gemcitabine and Gemcitabine/Nab-paclitaxel than were with FOLFIRINOX. Conclusion: The median Progression free survival is better for the Gemcitabine/Nab-paclitaxel and FOLFIRNOX than for Gemcitabine alone. Also, adverse effects are more common with FOLFIRINOX than with other first-line chemotherapeutic agents.
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e14613 Background: FOLFIRINOX improves overall survival compared to gemcitabine in patients with metastatic PCa. We retrospectively evaluated the feasibility of using induction FOLFIRINOX followed by chemoXRT to improve resectability in borderline resectable PCa. Methods: All patients with borderline resectable, biopsy-proven PCa treated with the FOLFIRINOX between 1/2009 -11/2011 were reviewed. Borderline resectable PCa was defined by computerized tomography (CT) imaging as tumor-induced SMA abutment of <180 degrees, SMV occlusion, or findings suspicious but not diagnostic for metastatic disease. CT imaging was obtained following induction chemotherapy and after chemoXRT prior to surgery. Results: Twelve patients with borderline resectable disease were treated with FOLFIRINOX induction (median of 4 cycles [range 3-8]). Chemotherapy details are listed in table 1. Tumors in 9 patients had SMA abutment or SMV occlusion and the median pre-treatment CA 19-9 was 297 U/ml (1-3432 U/ml ). Following induction chemotherapy, all patients proceeded to chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n=8] or capecitabine [n=4]). The median CA 19-9 reduction following systemic therapy alone was 58%. One patient did not complete chemoXRT due to infectious and hematologic toxicities. Following all neoadjuvant treatment, 7 (58%) of the 12 patients underwent successful PD. All 7 patients who underwent PD had an RO resection and only one patient had lymph node metastases. The median survival has not been met with median follow up of 13 months. Conclusions: In medically fit patients with borderline resectable PCa, induction FOLFIRINOX followed by chemoXRT is feasible and may facilitate a margin negative resection and histologic response in regional lymph nodes. [Table: see text]
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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.
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