Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy

Abstract

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.

Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

“…In 2011, the PRODIGE4/ ACCORD11 trial showed that FOLFIRINOX led to longer survival rates when compared to gemcitabine monotherapy 24 . In 2018, a study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX 25 . This study assessed a total of 51 patients treated from January 2014 until May 2018.…”

Prognostic and predictive factors in pancreatic cancer

“…Considering patients that received modified FOLFIRINOX, Yamada et al [98], found that the development of neutropenia after chemotherapy correlates with better OS. Moreover, there was a significant correlation between OS and the grade of neutropenia.…”

Chemotherapy-Induced Reduction of Neutrophil-to-Lymphocyte Ratio Is Associated With Better Survival in Pancreatic Adenocarcinoma: A Meta-Analysis

“…Neutropenia, as well as NLR decrease, indicate systemic inflammation receding. 38 , 39 The timing of neutropenia is an independent predictor of prognosis in metastatic colon cancer patients who received mFOLFOX6. Moreover, patients with early-onset and late-onset chemotherapy-induced neutropenia (CIN) had longer survival than patients without CIN.…”