More than a year ago (10/22/15), the U.S. Food and Drug Administration approved a modified form of the FOLFIRINOX regimen as a second line treatment for patients with metastatic pancreatic cancer (ductal adenocarcinoma of the pancreas) whose gemcitabine-based therapy had failed. We reported this development Here.
The modified FDA-approved regimen was different from the “standard” FOLFIRINOX for pancreatic cancer in that the oxaliplatin element was dropped, and the irinotecan was substituted with a liposomal irinotecan known as Onivyde (by Merrimack Pharmaceuticals, and known earlier as MM-398 and PEP02). The concept underlying this modification was aimed at seeing if similar or improved efficacy could be achieved in the treatment of advanced pancreatic cancer with a lessening of the tough side-effects of the multi-drug chemotherapy regimen.
The data related to this approval was primarily gleaned from the so-called NAPOLI-1 clinical trial for pancreatic cancer which was essentially fully available in November 2015, but was finally more widely available in the February 6, 2016 issue of the journal Lancet. The primary authors and researchers were world-wide in scope, and the pancreatic cancer research entities included TGen, Merrimack Pharmaceuticals, and Washington University among many others. The results were promising, and as promised.
Most of the subsequent recent research related to this or related drug regimens for pancreatic cancer have been either heavily oriented to reviews of the NAPOLI-1 results, or a further explication of the properties and effects of liposomal irinotecan, Onivyde.
One interesting more stand-alone study was done by Ohio State University, Emory University and Israeli researchers as published in the April, 2016 issue of the British Journal Medical Oncology. They compared the Onivyde modified FOLFIRINOX regimen (sans oxaliplatin) with 5-fluorouracil/leucovorin “alone” in the treatment of metastatic pancreatic cancer in a forty pancreatic cancer patient cohort who had previously failed gemcitabine therapy. The median progression free survival of the modified regimen was 2.59 months, and the median overall survival duration was noted as 4.75 months.
The authors concluded that the Onivyde modified FOLFIRINOX treatment regimen in the context of heavily pre-treated advanced pancreatic cancer patients appeared to confer survival advantage with reasonably tolerable side-effects.
Thus, the confirmation of the possible advantages of modified FOLFIRINOX, including liposomal irinotecan, as second line after gemcitabine failure in the treatment of advanced pancreatic cancer as was suggested by the NAPOLI-1 study continues to appear promising. Further research, confirmation and creativity is eagerly awaited.
Dale O’Brien, MD