Pancreatic cancer is notoriously difficult to treat. One problem is drug delivery, because pancreatic cells can cluster in a nest of scar-like tissue.
“If you can improve the drug delivery in pancreatic cancer, then you may have a chance to alter the nature course of this disease,” says Andrea Wang-Gillam, a GI oncologist with a strong focus on pancreatic cancer at Washington University in St. Louis and an author of a new study, which points to a way forward in improving second-line treatment for metastatic pancreatic cancer patients.
She and her colleagues reported at the European Society for Medical Oncology 2014 World Congress on Gastrointestinal Cancer, held this summer in Barcelona, that adding MM-398 to the standard treatment for patients who had already received gemcitabine-based regimen improves overall survival.
MM-398 consists of around 80,000 irinotecan molecules packed into a nano-size capsule made of liposome. Irinotecan is thought to disrupt proper working of DNA in tumour cells.
The current NAPOLI-1 trial is a global randomised Phase III trial that compares standard treatment with 5-fluorouracil (5FU)-leucovorin, MM-398 alone and MM-398 with 5FU/leucovirin in patients with diseases that have progressed on gemcitabine-based therapy.
Packing the irinotecan into the nano-capsule helped with the pharmacodynamics and pharmacokinetic features of the drug, explains Wang-Gillam. “It helps with better drug uptake at the tumour site, as well as sustaining the drug in circulation longer, which are favourable features for a drug delivery in pancreatic cancer and cancer in general.” It also converted into more of the active metabolic SN38 at the tumour site.
Overall survival was significantly improved with the combination of MM-398 plus 5FU-leucovorin compared with 5FU-leucovorin alone in the new study. The average overall survival was 6.1 months with the combination regimen compared with 4.2 months in the group receiving standard treatment with 5FU-leucovorin alone. Progression-free survival was boosted significantly, from 1.5 months with the standard therapy to 3.1 months in patients receiving MM-398 plus 5FU-leucovorin.
Patients with metastatic pancreatic cancer or pancreatic cancer in general have very limited options, Wang-Gillam notes: “These patients just simply don’t do well.” Now there is another viable option.
“Community organisations for pancreatic cancer are very interested in this drug,” says Wang-Gillam, who hopes MM-398, developed my Merrimack Pharmaceuticals, can be submitted for FDA approval soon.
In her own practice, presently 30% of patients receive a Folfirinox-like regime, with the remainder receiving gemcitabine-based therapy. Gemcitabine was approved the front-line treatment pancreatic cancer in 1997. Approximately only half of patients who progress on first-line therapy could receive the second-line therapy.