Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

Abstract

Background There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). This study aimed to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and investigate prognostic factors for survival. Methods From 2015–2019, we retrospectively reviewed the medical records of patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m 2 , intravenous irinotecan 150 mg/m 2 , and continuous infusion of 5-fluorouracil 2,400 mg/m 2 for 46 hours without bolus infusion) until disease progression, patient refusal, or unacceptable toxicity. Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2-9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8-5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5-100%), 77.2% (range 38.1-100%), and 85.9% (range 36.9-100%), respectively. Grade 3-4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6-16.3) and 7.6 months (95% CI 4.1-10.5) for the good prognostic factors, 6.5 (95% CI 5.5-10.0) and 3.6 months (95% CI 2.7-4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9-6.6) and 1.7 months (95% CI 0.9-4.3) for the poor prognostic factors, respectively. Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S‐1 as second‐line chemotherapy in metastatic pancreatic cancer

“…In previous studies in the single-arm setting, the FOLFIRINOX regimen, including mFOLFIRINOX, showed favorable treatment outcomes as a second-line chemotherapy after the failure of GEM-based chemotherapy. 17,23,24,26,27 Response rates, PFS, and OS in patients with MPC were 10.6-22.2%, 2.8-5.4 months, and 7.0-9.8 months, respectively. 17,23,27 However, limited data exist regarding the direct comparison between FOLFIRINOX and fluoropyrimidine, including S-1.…”

“…17,23,24,26,27 Response rates, PFS, and OS in patients with MPC were 10.6-22.2%, 2.8-5.4 months, and 7.0-9.8 months, respectively. 17,23,27 However, limited data exist regarding the direct comparison between FOLFIRINOX and fluoropyrimidine, including S-1. 28 In our current study of 78 patients with metastatic pancreatic adenocarcinoma after GnP failure, we observed significantly favorable response rates and PFS in the mFOLFIRINOX group compared with the S1 group.…”

“…We also examined 8-month survival rates, which were set according to the median OS in previous reports on single-arm FOLFIRINOX as a second-line chemotherapy. 17,23,24 Data from patients who were alive at the end of the follow-up period (December 2020) were censored. The study protocol was approved by the Institutional Review Board at Osaka International Cancer Institute (approval no.…”

“…Although mFOLFIRINOX following GnP failure could be a promising strategy because both GnP and mFOLFIRINOX have shown favorable outcomes, limited data are available regarding sequential therapy with GnP and mFOLFIRINOX. 17 In Japan, S-1, an oral fluoropyrimidine, has been widely used as a second-line therapy because S-1 has antitumor activity with tolerable toxicity against GEM-refractory PC. [18][19][20][21] In this study, we aimed to examine the efficacy and safety of mFOLFIRINOX in comparison with S-1 as a second-line chemotherapy in patients with metastatic adenocarcinoma of the pancreas after GnP failure.…”

Multiple-line Chemotherapy for a Patient with Unresectable Mucinous Cystic Neoplasm of the Pancreas

“…Several studies investigated the efficacy of modified FOLFIRINOX in patients with GEM-refractory PDAC (19)(20)(21). Sawada et al reported the efficacy and good tolerability of modified FOLFIRINOX as second-line therapy after GnP (22). Although FOLFIRINOX poses a risk of serious adverse events, these studies have shown that it can be safely administered when doses are reduced.…”