title: Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.
abstract: Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.
authors.affiliation: Department of Medical Oncology, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University Wexner Medical Center, A454 Startling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bupathi
authors.affiliation: Department of Medical Oncology, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University Wexner Medical Center, A454 Startling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Ahn
authors.affiliation: Department of Medical Oncology, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University Wexner Medical Center, A454 Startling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University Wexner Medical Center, A454 Startling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Ciombor
authors.affiliation: Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Stephens
authors.affiliation: Department of Pharmacy, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Reardon
authors.affiliation: Winship Cancer Institute, Emory University, 1365-C Clifton Rd NE, Atlanta, GA, USA.|Davidoff Cancer Center, Rabin Medical Center, Derech Ze'ev Jabotinsky 39, 4941492, Petach Tikva, Israel.
authors.forename: D A
authors.initials: DA
authors.lastname: Goldstein
authors.affiliation: Department of Medical Oncology, Richard Solove Research Institute and James Cancer Hospital, The Ohio State University Wexner Medical Center, A454 Startling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA. Tanios.Saab@osumc.edu.
authors.forename: T
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D003365:Costs and Cost Analysis; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Adverse effects; Cancer; FOLFIRI; Gemcitabine; Pancreatic; Tolerability