title: Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma.
abstract: Intravenous liposomal irinotecan injection (Onivyde®) is approved for use in combination with 5-fluorouracil and leucovorin (5-FU/LV) in patients with metastatic pancreatic adenocarcinoma that has progressed following gemcitabine-based therapy. Liposomal irinotecan is a liposome-encapsulated formulation of the topoisomerase-1 inhibitor irinotecan, developed to overcome the pharmacological and clinical limitations of non-liposomal irinotecan. In the pivotal multinational, phase III NAPOLI-1 trial in patients with metastatic pancreatic adenocarcinoma that had progressed following gemcitabine-based therapy, liposomal irinotecan in combination with 5-FU/LV significantly prolonged median overall survival (OS; primary endpoint) and median progression-free survival (PFS) at the time of the primary analysis (after 313 events) and final analysis (after 382 events) compared with 5-FU/LV control therapy. The objective response rate was also significantly higher in the liposomal irinotecan plus 5-FU/LV group than in the control group. Liposomal irinotecan-based combination therapy had a manageable safety profile; the most common treatment-emergent adverse events (TEAEs) of grade ≥3 severity were haematological or gastrointestinal in nature. The incidence of neutropenic sepsis was low. In a setting where there is a paucity of second-line treatment options, liposomal irinotecan in combination with 5-FU/LV is an important emerging treatment option for metastatic adenocarcinoma of the pancreas that has progressed following gemcitabine-based therapy.
authors.affiliation: Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. demail@springer.com.
authors.forename: Yvette N
authors.initials: YN
authors.lastname: Lamb
authors.affiliation: Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Scott
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008081:Liposomes; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D008081:Liposomes; D003841:Deoxycytidine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine