Locally advanced pancreatic cancer responds to FOLFIRINOX

Treatment with FOLFIRINOX chemotherapy followed by chemoradiation in locally advanced pancreatic cancer (LAPC) was associated with conversion to resectability in more than 20% of patients in a small study. However, the toxicity of this therapy as well as recurrences following resection raise important questions regarding the best treatments for people with LAPC, caution the study authors.

FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) is associated with improved response rate, progression-free survival, and overall survival in persons with metastatic pancreatic cancer. However, this treatment has not been studied extensively in persons with LAPC, according to a statement from the publishers of The Oncologist, in which the new findings appear. As noted in the statement, nearly one-third of patients with newly diagnosed pancreatic cancer present with locally advanced disease, which is associated with a median overall survival of approximately 1 year.

Medical oncologist Jason E. Faris, MD, of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts, and colleagues reported on the retrospective experience of 22 patients with LAPC at that facility. All began treatment with FOLFIRINOX between July 2010 and February 2012. For 20 of the patients, FOLFIRINOX was followed by chemoradiation with continuous-infusion 5-FU or capecitabine and intensity-modulated radiation therapy (50.4 Gy). Patients received a median of 8 cycles of neoadjuvant FOLFIRINOX, including a median of 2.5 full-dose cycles.

Over the median follow-up of 19.3 months, overall response rate was 27.3% and median progression-free survival was 11.7 months while on FOLFIRINOX and 36.4% after chemoradiation. Following neoadjuvant FOLFIRINOX and chemoradiation, five of 22 patients (23%) were able to undergo an R0 resection (complete resection with no microscopic residual tumor). However, three of those five patients experienced distant recurrence within 5 months (median 81 days postoperatively).

One-third of the patients (seven, or 32%) required at least one emergency-department visit or hospitalization due to FOLFIRINOX toxicity, and two patients discontinued FOLFIRINOX due to its toxicity.

“We believe the results are promising for this strategy, in a group of patients where the historical possibility for resection is low and the overall prognosis is quite dismal,” affirmed Faris in the publisher's statement. “However, this promise must be evaluated against the recurrences observed in the patients who were able to undergo resection, as well as the toxicity signal that is present with this multidrug regimen.”

Faris added that prospective evaluation of therapies for persons with LAPC will be critical to improving treatments and outcomes for this group of patients.

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