Liposomal Irinotecan, S-1, and Oxaliplatin in Advanced Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma is the seventh leading cause of cancer-related mortality worldwide, and it carries dismal prognosis with a 5-year survival rate of 1-2%. The pivotal ACCORD11 trial, FOLFIRINOX (oxaliplatin, irinotecan, 5-FU and leucovorin) has become the standard of care for patients with locally advanced or metastatic pancreatic adenocarcinoma. In daily practice, modified version of FOLFIRINOX (mFOLFIRINOX) with reduced dose of irinotecan to 150 mg/m2 and omission of bolus 5-FU has been widely used to enhance the dose intensity and safety profiles. Despite of proven efficacy of mFOLFIRINOX in locally advanced or metastatic pancreatic cancer, further improvement in the efficacy outcomes are needed, considering that median overall survival of metastatic pancreatic cancer patients treated with FOLFIRINOX in the phase 3 trial was less than 1 year. Considering that mFOLFIRINOX often require placement of central catheterization or repeated hospitalization for continuous 5-FU infusion, novel regimens improving mFOLFIRINOX in the viewpoint of patient's quality of life is also needed. This may enhance the patient's compliance on the treatment and maximize the clinical outcomes. Liposomal irinotecan (nal-IRI) is the novel agent enhancing the drug delivery of irinotecan and approved for the management of gemcitabine-progressed metastatic pancreatic cancer patients. Considering the hostile tumor microenvironment of pancreatic adenocarcinoma, nal-IRI may have enhanced anti-tumor activity compared to conventional irinotecan, although there are no head-to-head comparison clinical trial data, yet. Investigators previously developed oral fluoropyrimidine-based triplet regimen (oxaliplatin, irinotecan and S-1) and investigated in 32 patients with advanced biliary tract cancer. This regimen was well tolerated and showed favorable efficacy outcome as first-line therapy with overall response rate of 50%. In present study, investigators evaluate the safety and efficacy of OIS-derived NASOX regimen (nal-IRI, S-1, oxaliplatin) in advanced pancreatic cancer. NASOX regimen contains nal-IRI, which has recently been proven effective in pancreatic cancer. If NASOX, which is more convenient than FOLFIRINOX, proves its safety and effectiveness, it may provide an attractive alternative for pancreatic cancer patients.