O2-16-2Phase 2 study of 1st-line modified FOLFIRINOX in unresectable advanced pancreatic cancer: Multicenter prospective study

FOLFIRINOX (FX) was reported as effective treatment for unresectable advanced pancreatic cancer (UAPC). However, because of combination chemotherapy, FX is associated with a higher incidence of adverse events (AEs). In a phase 2 study in Japan showed higher incidence of grade(G) 3 or 4 AEs including febrile neutropenia (FN: 22.2%). Modified FX (mFX) by omitting the bolus 5-FU and reducing irinotecan may decrease AEs and can be more effective than FX by improving treatment compliance. To assess the safety and efficacy of first-line mFX for UAPC. his study was multicenter prospective phase 2 study. Inclusion criteria were 1) age of 20-75 y.o., 2) ECOG PS of 0 or 1 and 3) pathologically confirmed pancreatic adeno- or adenosquamous-carcinoma between 10/2014 and 3/2016. Exclusion criteria were followings: 1) h/o chemotherapy or 2) homozygous UGT1A1*28/*6 or heterozygous UGT1A1*6 and *28. Treatment with mFX (i.v. infusion of 85mg/m2 oxaliplatin, 150mg/m2 irinotecan, and 200mg/m2 l-leucovorin, followed by a 46-h continuous infusion of 2400mg/m2 5-FU) was given every 2 weeks. The primary endpoint was response rate (RR). The secondary endpoints were overall survival (OS), progression-free survival (PFS) and safety. 31 patients (18 men, median age of 64 y.o.) were enrolled. PS was 0 in 25 and 1 in 6. The tumor was located in the head in 15 and the body/tail in 16. Biliary stent was placed in 8. Metastasis was recognized in 21. The median number of treatment cycles was 13. The response rate was 38.7%. The median follow-up time was 18.4 months. The median OS was 15.2 months, and the median PFS was 7.1 months. G3 or 4 AEs included neutropenia (84%), FN (16.1%), peripheral sensory neuropathy (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%) and vomiting (3.2%). Compared to full-dose FX, mFX may reduce G3 or 4 AEs with comparable efficacy. Thus, mFX may improve the quality of life in patients with UAPC.