The move away from surgical diagnosis to radiographic criteria in many and now even most efforts at the staging of cancer of the pancreas carries a number of somewhat unspoken but profound consequences, one being efforts to find ways to downstage the diagnosis so as to profitably utilize surgery in locally advanced and borderline resectable pancreatic cancer. We have thus seen the rise of the use of chemotherapy alone or in combination with other modalities in induction neoadjuvant treatment in order to accomplish this.
But this is somewhat new territory. For example, it is not clear what the optimal duration of such neoadjuvant therapy should be. Thus, it comes with great interest that Donahue, Reber and colleagues at UCLA have reviewed their experience in this realm over the past two decades – with a rather startling finding: that prolonged duration of neoadjuvant therapy appears to confer a large benefit in many cases. This work has been E-published on December 4, 2013 in the journal JAMA Surgery (formerly Archives of Surgery).
The UCLA researchers reviewed patients treated at their institution from 1992 until 2011, identifying 49 patients who were Stage III / locally advanced or who were considered borderline resectable, AND who completed preoperative treatment – with a median duration of 7.1 months. A remarkable 75.5% of these patients were able to later undergo surgery. Most of these patients were lymph node negative at the time of surgery. The median overall survival duration of this studied group was 40.1 months.
Prolonged pre-surgical therapy appears to offer large benefit to select patients. This finding requires further study, but is highly encouraging.
Dale O’Brien, MD
Since the May 12, 2011 New England Journal of Medicine article that reported the possible superiority of the 5-FU based four-drug FOLFIRINOX regimen over gemcitabine in the treatment of metastatic pancreatic cancer (and subsequent FDA approval), researchers have been at work trying to discover the best use of this information – and ways to perhaps improve on it. A case in point is the blog entry just prior to this one (FOLFIRINOX for neoajuvant therapy in pancreatic cancer).
Also, we have reported on research of chemotherapy combinations that contain similar but fewer drug agents, such as the ones termed OFF and SOX. These are essentially modified FOLFIRINOX regimens. But there has arisen the term “Modified FOLFIRINOX Regimen” by which researchers appear to mean that tiny (to date) body of research on smaller tweaks to the standard FOLFIRINOX combination: oxaliplatin – 85 mg per M2 (body-surface area); irinotecan – 180 mg/ M2; leucovorin, 400 mg/M2; and fluorouracil (5-FU) – 400 mg/M2 given as a bolus followed by 2400 mg/M2 given as a 46-hour continuous infusion.
El-Rayes and colleagues at Emory University have published a study involving such a modified FOLFIRINOX regimen in the November issue of the journal Pancreas. They postulated that eliminating the bolus portion of the 5-FU and adding hematopoietic growth factor to FOLFIRINOX might continue to provide the efficacy of the drug-combination while improving the safety profile of the side-effects. They looked at 60 patients with pancreatic cancer in various stages of disease who were treated using this modified combination.
The authors found that the median overall survival duration for these patients with metastatic pancreatic cancer treated with this modified FOLFIRINOX regimen was 9.0 months. Also, importantly, the safety profile did appear to be improved. The researchers suggest that this regimen can be given more safely than standard FOLFIRINOX, and without losing efficacy.
This is an interesting finding demanding further research.
Dale O’Brien, MD
The idea behind treating surgically unresectable and borderline resectable pancreatic cancer with chemotherapy or chemoradiation is that some minority of cases will thereupon improve to the point of now being deemed amenable to surgery, with its typically more favorable outcome. This is generally the point then of so-called neoadjuvant therapy.
As the 5-FU based four-drug FOLFIRINOX regimen appears to show improved outcomes for advanced pancreatic cancer over gemcitabine alone, Bahary and colleagues at the University of Pittsburgh used FOLFIRINOX as neoadjuvant therapy in unresectable and borderline resectable pancreatic cancer. The results were published in the September edition of the Journal of Surgical Oncology.
The researchers treated 21 such pancreatic cancer patients with the drug combination; seven patients were then able to progress to surgery (two of these patients were initially found to have been unresectable). An additional two patients were deemed fit for surgery who were treated with both FOLFIRINOX and stereotactic body radiation therapy.
The authors found the results of FOLFIRINOX neoadjuvant treatment for surgically unresectable and borderline resectable pancreatic cancer as encouraging. This approach is certainly worthy of further study.
Dale O’Brien, MD