Abstract:BackgroundFOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance.AimsTo assess the safety and efficacy of first-line mFX for unresectable advanced … Show more
“…Only 70 studies were eligible upon abstract screening. After full-text screening, only 11 studies remained, and they were included in the final analysis 20 – 30 . Figure 1 Flow chart for study search (PRISMA diagram).…”
FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.
“…Only 70 studies were eligible upon abstract screening. After full-text screening, only 11 studies remained, and they were included in the final analysis 20 – 30 . Figure 1 Flow chart for study search (PRISMA diagram).…”
FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.
“…Regarding neutropenia, 77.8% of patients experienced severe neutropenia in a Japanese phase II study of sFOLFIRINOX for chemotherapy-naïve MPC, which is similar to our study’s findings[ 22 ]. In addition, most studies conducted in Asian countries reported severe neutropenia in > 65% of patients[ 23 - 26 ], which was more frequent than that in reports from western countries (11.0%-45.7%)[ 7 , 27 - 29 ]. These results suggest that Asians may be prone to severe FOLFIRINOX-related neutropenia, and dose adjustment is an option that should be considered when treating patients belonging to the Asian population.…”
AIMTo directly compare the efficacy and toxicity of standard-dose FOLFIRINOX (sFOLFIRINOX) and modified-dose FOLFIRINOX (mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODSOne hundred and thirty pancreatic cancer patients who received sFOLFIRINOX (n = 88) or mFOLFIRINOX (n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated and compared using Pearson’s chi-square test, Kaplan-Meier plot and log-rank test. The adverse events (AEs) were evaluated, and severe (≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTSThe mFOLFIRINOX group included more female patients (30.7% vs 57.1%; P = 0.004) and older patients [age (median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups (ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups (PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia (83.0% vs 66.7%; P = 0.044), anorexia (48.9% vs 28.6%; P = 0.029) and diarrhea (13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSIONmFOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.
“…In these patients, dose escalation was not performed even if the adverse events disappeared. The criteria for dose reduction was chosen according a Japanese phase II study on modified FOLFIRINOX [ 6 ]. Briefly, treatment was delayed when one or more of the following adverse events occurred: grade 3–4 neutropenia or thrombocytopenia, febrile neutropenia, total bilirubin >3.0 mg/dL, aspartate transaminase and alanine transaminase >150 U/L, creatinine >1.5 mg/dL, grade 3–4 peripheral neuropathy, and grade 3–4 diarrhea.…”
Section: Methodsmentioning
confidence: 99%
“…To reduce the incidence of toxicities associated with FOLFIRINOX, the chemotherapy regimen has been modified by omission the bolus injection of 5-FU and/or reducing the dose of irinotecan without reducing the clinical response [ 5 , 6 , 7 , 8 , 9 ]. 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 ].…”
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.
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