A phase II study of FOLFIRINOX with primary prophylactic pegfilgrastim for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer

Abstract

Background Although FOLFIRINOX is currently one of the standard therapies for chemotherapy-naïve patients with metastatic pancreatic cancer (MPC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to evaluate the safety and efficacy of primary prophylactic pegfilgrastim with FOLFIRINOX in Japanese MPC patients. Methods FOLFIRINOX (intravenous oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, levofolinate 200 mg/m2, 5-fluorouracil (5-FU) bolus 400 mg/m2 and 5-FU 46 h infusion 2400 mg/m2) and pegfilgrastim 3.6 mg on day 4 or 5, every 2 weeks was administered to previously untreated MPC patients. The primary endpoint was the incidence of FN during the first 3 cycles. The planned sample size was 35 patients, but the trial was predefined to discontinue enrollment for safety if 4 patients developed FN. Results At the enrollment of 22 patients, 4 patients developed FN in the first cycle, resulting in an incidence of FN of 18% {95% confidence interval [CI], 0.5–40.3%}, and enrollment was discontinued early. The incidence of grade 3 or higher neutropenia was 36.4%. Median relative dose intensities during the initial 3 cycles of oxaliplatin, irinotecan, bolus 5-FU, infusional 5-FU, and levofolinate maintained high (100%, 89.0%, 100%, 66.0%, and 100%, respectively). Response rate and median overall survival were 54.5% (95% CI 32.7–74.9) and 15.7 months (95% CI 7.9–18.8), respectively. Conclusions This phase II study could not demonstrate any reduction in the incidence of FN, nevertheless some patients experience benefits for efficacy by maintaining dose intensity using prophylactic pegfilgrastim. Trial registration http://www.umin.ac.jp/ctr/index-j.htm, UMIN000017538. Date of registration: May/13/2015

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis

“…However, data from subsequent prospective and retrospective studies have shown highly variable rates of G3/4N, ranging from 6 to 78% -Table 5. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] In our study, only 23% of the patients developed GN3/4. This is likely related to the relatively high frequency of PP (61%), which showed to be associated with a significantly lower risk of G3/4N (OR = .13) in the multivariate logistic regression.…”

“…10,34 However, rates of NF during treatment with FOLFIRINOX are highly variable in the literature, ranging from 0 to 26% -Table 5. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Indeed, the higher figures observed in some retrospective studies have led the NCCN guideline to advise in favor of PP for patients treated with FOLFIRINOX. 1 In our study, only 6.5% of the patients experienced FN and even for those who did not receive PP, the frequency of FN was relatively low (8%).…”

Impact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer

“…72,73 The median OS of patients in this Canadian cohort who received gemcitabine 1 nab-paclitaxel after firstline FOLFIRINOX was also higher (19.3 months; 95% CI, 12.6 2 26.0 months) than that in a 2015 clinical trial assessing prophylactic G-CSF use in patients with metastatic PDAC treated with FOLFIRINOX (15.7 months; 95% CI, 7.9-18.8 months). 72,74 In practice, the indications for G-CSF use are dependent on clinical judgment and perceived risk of febrile neutropenia and infectious complications. The potential long-term negative consequences of G-CSF administration in patients with PDAC warrant careful reevaluation of current growth factor support practice guidelines to help clarify its appropriate use.…”

The influence of UGT1A1 polymorphisms on modified FOLFIRINOX dose in double-variant-type patients with advanced pancreatic cancer

“…A recent systematic review showed that prophylactic use of G-CSF reduces the rates of FN, dose reduction, and treatment delay [ 21 ]. Our group previously conducted a phase II trial to evaluate the safety and efficacy of primary prophylactic pegfilgrastim in patients with metastatic pancreatic cancer who received FOLFIRINOX [ 22 ]. However, FN occurred in 18.0% and previously, we could not demonstrate the efficacy of pegfilgrastim addition to FOLFIRINOX; the DV patients were excluded.…”