A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer

// Kensaku Yoshida 1 , Takuji Iwashita 1 , Shinya Uemura 1 , Akinori Maruta 1 , Mitsuru Okuno 1 , Nobuhiro Ando 2 , Keisuke Iwata 2 , Junji Kawaguchi 3 , Tsuyoshi Mukai 3 and Masahito Shimizu 1 1 First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan 2 Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan 3 Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan Correspondence to: Takuji Iwashita, email: takuji@w7.dion.ne.jp Keywords: adverse events; febrile neutropenia; dose modification; biliary drainage; risk factor Received: August 24, 2017 Accepted: November 13, 2017 Published: November 30, 2017 ABSTRACT Background: FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance. Aims: To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer. Patients and methods: This was as a multicenter prospective phase II study in chemotherapy-naïve Japanese patients with pathologically confirmed unresectable advanced pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85 mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by 46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2 weeks. The primary endpoint was the response rate. The secondary endpoints were overall survival, progression-free survival, and safety. Results: Thirty-one patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment cycles were administered during a median follow-up period of 14.2 months. The response rate, median overall survival, and median progression-free survival were 38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting (3.2%). Conclusion: Compared to FX, mFX may result in fewer Grade 3 or 4 non-hematological AEs, with a comparable response rate. However, further efforts might be required to reduce hematological AEs.