Safety and efficacy of dose-modified FOLFIRINOX on toxicity and effectiveness in Japanese patients with unresectable pancreatic cancer (PC).

Abstract

422 Background: FOLFIRINOX has been shown superior to GEM in terms of OS, PFS and/or RR for treatment of metastatic PC in Accord 11, and this regimen has become the standard of care for the first-line chemotherapy. However, the major disadvantage of FOLFIRINOX is significantly higher toxicity, and, in particular, quite higher incidence of neutropenia (78%) and febrile neutropenia (22%) was observed in the PII clinical trial of FOLFIRINOX performed in Japan (LOHP-PII-05, JSCO 2013). Thus, in clinical practice for the Japanese patients, it should be needed to make modification on this regimen in terms of dose reduction without compromising in its effectiveness. We evaluated the safety and efficacy of modified (m) FOLFIRINOX in Japanese patients with unresectable locally advanced PC (LAPC), metastatic PC (MPC), and/or postoperative recurrence. Methods: The modifications to FOLFIRINOX include discontinuation of the bolus 5-FU and dose-reduction (25%) of irinotecan. 36 patients with unresectable LAPC, MPC and postoperative recurrence were treated with mFOLFIRINOX, and toxicity and efficacy were evaluated. Results: Patient characteristics were as follows: LAPC/MPC/Postoperative recurrence 6/20/10; median age 65 years (range 39-75); male/female 27/9. Median number of cycles was 5 (range 1-28). Grade 3/4 toxicities included neutropenia (16.7%), leukopenia (13.9%), diarrhea (13.9%) and enteritis (11.1%) in order. Febrile neutropenia was only in 2 patients (5.6%). Both hematologic and non-hematologic toxicities were reduced, although diarrhea was observed in a bit higher incidence compared to those in LOHP-PII-05. The response rate and disease control rate evaluated in 28 patients were favorable, in LAPC, MPC and/or post operative recurrence, which were similar to those in LOHP-PII-05. In response of CA19-9 was evaluated in 26 patients. 20 patients (76.9%) showed a decline in CA19-9 levels from baseline, and a greater than 50% decline was noted in 15 patients (57.7%). Conclusions: mFOLFIRINOX has an improved safety profile with maintained efficacy in the selected population of MPC. mFOLFIRINOX has promising activity also in LAPC with respect to RR.