Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma

Jesus, Victor Hugo Fonseca de; Camandaroba, Marcos Pedro Guedes; Donadio, Mauro Daniel Spina; Cabral, Audrey; Muniz, Thiago Pimentel; Leite, Luciana de Moura; Sant’Ana, Lucas Ferreira

doi:10.21037/jgo.2018.04.02

Cited by 26 publications

(26 citation statements)

References 32 publications

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“…Instead, the patient-tailored FOLFIRI-NOX regimen used here confirmed its satisfactory tolerance we previously reported in advanced pancreatic adenocarcinoma [13], with no new safety issues observed in comparison with existing literature [17,18,30]. We speculate that the patient-tailored approach we adopted here, which recapitulates similar ones with FOLFIRINOX in pancreatic adenocarcinoma [13,31,32] displayed favorable tolerance profile thanks to the deal made between the decreased dose intensity of the three cytotoxics and the global duration of treatment, somewhat allegedly avoiding over-or under-exposure to the drugs [33]. Thus, median actual delivered dose intensities were of the order of~70% (Fig.…”

Section: Discussionsupporting

confidence: 82%

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer

et al. 2020

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Background: FOLFIRINOX is a pillar first-line regimen in the treatment of pancreatic cancer. Historically, biliary tract cancer (BTC) and pancreatic cancer have been treated similarly with gemcitabine alone or combined with a platinum compound. With growing evidence supporting the role of fluoropyrimidines in the treatment of BTC, we aimed at assessing the outcomes of patients (pts) with BTC on frontline FOLFIRINOX. Methods: We retrospectively analyzed data of all our consecutive patients with locally advanced (LA) or metastatic (M) BTC who were registered to receive FOLFIRINOX as a first-line therapy between 12/2013 and 11/2017 at Paul Brousse university hospital. The main endpoints were Overall Survival (OS), Time-to-Progression (TTP), best Objective Response Rate (ORR), Disease Control rate (DCR), secondary macroscopically-complete resection (res) and incidence of severe (grade 3-4) toxicity (tox). Results: There were 17 male (40%) and 25 female (60%) pts. aged 36 to 84 years (median: 67). They had PS of 0 (55%) or 1 (45%), and intrahepatic cholangiocarcinoma (CCA) (21 pts., 50%), gallbladder carcinoma (8 pts., 19%), perihilar CCA (7 pts., 17%), distal CCA (4 pts., 10%) and ampulloma (2 pts., 5%). BTC was LA or M in 10 (24%) and 32 pts. (76%) respectively. Biliary stent was placed in 14 pts. (33%). A median of 10 courses was given with median treatment duration of 6 months. There were no untoward toxicity issues, with no febrile neutropenia, emergency admission for toxicity or toxic death. We observed 12 partial responses (29%) and 19 disease stabilisations (45%). Six patients (14%) underwent secondary R0-R1 resection. Median TTP was 8 months [95%CL, 6-10] and median OS was 15 months [13-17]. Patients undergoing secondary resection displayed a 3-y disease-free rate of 83%. Conclusions: First-line FOLFIRINOX offers promising results in patients with LA and M-BTC. It deserves prospective evaluation to further improve outcomes for advanced BTC.

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Section: Discussionsupporting

confidence: 82%

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer

et al. 2020

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“…Recently, Schlick et al [26] evaluated 123 metastatic PC (mPC) patients who underwent FOLFIRINOX treatment, showing by multivariate analysis that BMI > 25 and CEA > 4 at the time of onset of advanced disease could be interpreted as independent negative prognostic factors for OS and for toxicity, also suggesting a role for clinical parameters in patient selection. Other parameters such as the neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, could be considered for selection, but further clinical studies are needed to support this [27], especially in an adjuvant setting.…”

Section: Discussionmentioning

confidence: 99%

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Galvano

Castiglia

Rizzo

et al. 2020

Cancers

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Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52–0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50–0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03–1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.

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“…However, different from these promising results, de Jesus et al have not found significant discrepancy in toxicity between patients with metastatic pancreatic adenocarcinoma treated with standard and modified FOLFIRINOX regimens, possibly due to patient selection and a higher dose reduction rate in the standard FOLFIRINOX arm. Moreover, the activities against metastatic pancreatic adenocarcinoma of the two regimens are similar in a retrospective study [41]. Therefore, the effective modification agent is still under exploration.…”

Section: Corresponding Measures To Override Limitations For Chemotherapymentioning

confidence: 99%

“…To decrease the accompanied toxicity and adverse effect of two prominent regimens, FOLFIRINOX and the doublet of gemcitabine and nab-paclitaxel, the modifications of the FOLFIRINOX regimen to decrease the toxicity profile and keep a similar anti-tumour effect as the standard one at the same time have been tested [9,41]. Mahaseth et al reported that modified FOLFIRINOX (discontinuation of the bolus 5-FU and administration of growth factors) has an improved safety profile, especially with respect to neutropenia, fatigue, and vomiting, with maintained efficacy in metastatic PDAC [42].…”

Section: Corresponding Measures To Override Limitations For Chemotherapymentioning

confidence: 99%

Mechanisms of drug resistance of pancreatic ductal adenocarcinoma at different levels

2020

Bioscience Reports

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Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours. In this review, the main mechanisms of drug resistance clinicians and investigators are dealing with during the exploitation and exploration of the anti-tumour effects of drugs in PDAC treatment are summarized. Corresponding measures to overcome these limitations are also discussed.

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Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma

Cited by 26 publications

References 32 publications

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Mechanisms of drug resistance of pancreatic ductal adenocarcinoma at different levels

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