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.

Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

“…Encapsulated into liposomes, irinotecan is stable for a longer period of time, resulting in increased accumulation in tumor tissue and thereby increasing its effect, as described further in Sect. 3.2 [ 87 ].…”

“…Finally, in pancreatic cancer, the combination of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is used for both first-line adjuvant and palliative treatment in which it was shown to be superior to gemcitabine monotherapy (median OS 11.1 months, RR 31.6%) [ 232 ]. Liposomal irinotecan has recently been approved as second-line treatment for metastatic pancreatic cancer for patients with progression on gemcitabine-based therapies [ 87 ]. Efficacy of this liposomal formulation needs to be explored further in other tumor types.…”

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

“…Intestinal bacteria may deconjugate it, and the free drug may then cause direct intestinal damage or alteration of intestinal flora . A liposomal formulation of 4 , Onivyde has also shown promise in combination therapy for pancreatic cancer …”

“…133 A liposomal formulation of 4, Onivyde has also shown promise in combination therapy for pancreatic cancer. 134 A full description of the complex SAR of CPT derivatives is beyond the scope of this review. A myriad of modifications to the core of 1 have been made, 105,[135][136][137][138][139][140][141][142][143] most of which were undertaken to improve solubility, lactone stability, or bioavailability.…”

A Theranostic Approach to Target Gastrin in Pancreatic Cancer

“… 9 Similarly, Onivyde (Merrimac Pharmaceuiticals Inc, Cambridge, MA), a nanoliposomal irinotecan formulation, currently is being evaluated in pancreatic cancer. 10 , 11 In this context, development of a targeted nanoconjugate, as studied by Burks et al, that can improve delivery of targeted siRNA to tumor cells is extremely timely.…”