SUMMARY: The American Cancer Society estimates that in 2016, over 53,000 people will be diagnosed with Pancreatic cancer in the United States and close to 42,000 patients will die of the disease. Some important risk factors for Pancreatic cancer include increasing age, obesity, smoking history, genetic predisposition, exposure to certain dyes and chemicals, heavy alcohol use and pancreatitis. The best chance for long term survival is complete surgical resection, although this may not be feasible in a majority of the patients, as they present with advanced disease at the time of diagnosis. Approximately 35% of patients with Pancreatic cancer have unresectable, locally advanced disease at diagnosis. Based on the National Cancer Data Base, the 5 year observed survival rate for patients diagnosed with exocrine cancer of the Pancreas is 14% for those with Stage IA disease and 1% for those with Stage IV disease.
In a previously published study (N Engl J Med 2011; 364:1817-1825), FOLFIRINOX regimen, a combination of Fluorouracil, Leucovorin, Irinotecan (CAMPTOSAR®) and Oxaliplatin (ELOXATIN®) was significantly superior to single agent Gemcitabine (GEMZAR®), as first-line therapy, in patients with metastatic Pancreatic cancer. FOLFIRINOX resulted in a significantly improved median Overall Survival (OS), median Progression Free Survival (PFS) and Objective Response Rate (ORR).
The researchers in this study evaluated the effectiveness of FOLFIRINOX as first-line treatment in patients with newly diagnosed, locally advanced, unresectable Pancreatic cancer. The authors searched large databases for studies which involved treatment-naive patients of any age, who had received FOLFIRINOX as first-line treatment for locally advanced Pancreatic cancer. They were able to include 689 patients from 13 studies, of whom 355 (52%) patients had locally advanced Pancreatic cancer. FOLFIRINOX regimen consisted of Oxaliplatin 85mg/m2 IV over 2 hours, followed by Leucovorin 400mg/m2 IV over 2 hours given concomitantly with Irinotecan 180mg/m2 IV over 90 minutes, followed by 5-FU 400 mg/m2 IV bolus and 5-FU 2400 mg/m2 given as a 46 hour continuous infusion, with this cycle repeated every 2 weeks. The median number of administered cycles ranged from 3-11 cycles. In his retrospective review, the authors looked at Overall Survival as the Primary outcome. Secondary outcomes were Progression Free Survival, rates of Grade 3 or 4 toxicities, proportion of patients who underwent Radiotherapy or Chemoradiotherapy, surgical resection after FOLFIRINOX and R0 resection (margin-negative resection microscopically, with no gross or microscopic tumor present in the primary tumor bed).
It was noted that across studies, the pooled median OS was 24.2 months, median PFS was 15 months, Grade 3 or 4 adverse events were 60 events per 100 patients and no deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent Radiotherapy or Chemoradiation after FOLFIRINOX ranged from 31% to 100% across studies and the pooled proportion of patients who received any Radiotherapy treatment was 63.5%. The pooled proportion of patients who had surgical resection was 25.9% and the pooled proportion of patients who had R0 resection was 78.4%. There was no significant correlation found across studies, between the median number of FOLFIRINOX cycles administered and median Overall Survival.
The authors concluded that patients with locally advanced Pancreatic cancer treated with FOLFIRINOX had a longer median Overall Survival (24.2 months), compared with single agent GEMZAR® (6-13 months) and future studies should establish which patients might benefit from Radiotherapy or Chemoradiotherapy or Surgical resection, following treatment with FOLFIRINOX. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Suker M, Beumer BR, Sadot, F, et al. Lancet Oncol 2016;17:801-810.
