From the Guidelines
mFOLFIRINOX is generally preferred over Gemcitabine and Abraxane as a neoadjuvant treatment for pancreatic cancer in patients with good performance status who can tolerate its higher toxicity profile. This recommendation is based on the results of the PRODIGE trial, which showed dramatic improvements in both median progression-free survival (PFS) and median overall survival (OS) in favor of FOLFIRINOX compared to gemcitabine in patients with metastatic pancreatic cancer and good performance status 1.
Key Considerations
- mFOLFIRINOX consists of modified doses of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, typically administered every 2 weeks for 2-3 months before surgery.
- Gemcitabine plus nab-paclitaxel is usually given weekly for 3 weeks followed by 1 week off, also for 2-3 months preoperatively.
- mFOLFIRINOX has shown superior tumor response rates and R0 resection rates in several studies, potentially offering better survival outcomes.
- However, it causes more significant side effects including neutropenia, fatigue, diarrhea, and neuropathy.
- Gemcitabine plus nab-paclitaxel is better tolerated and remains an excellent option for older patients or those with comorbidities who may not tolerate the toxicity of mFOLFIRINOX.
Patient Factors
- Age
- Performance status
- Comorbidities
- Patient preference
- The choice between these regimens should be individualized based on these patient factors after thorough discussion of the risk-benefit profile of each approach 1.
Neoadjuvant Therapy
- Neoadjuvant therapy should preferably be administered at or coordinated through a high-volume center.
- Upfront resection in patients with borderline resectable disease is no longer recommended.
- The best regimens to use in the borderline neoadjuvant setting are unknown, but acceptable regimens include FOLFIRINOX, gemcitabine/albumin-bound paclitaxel, and gemcitabine/cisplatin (for patients with BRCA1/2 or other DNA repair mutations) 1.
From the Research
Neoadjuvant Treatments for Pancreatic Cancer
- The standard approach to neoadjuvant treatment for pancreatic cancer involves choosing between two combination regimens: modified FOLFIRNOX (mFOLFIRINOX) and gemcitabine/nab-paclitaxel (Gemcitabine and Abraxane) 2.
- Nonrandomized data indicate that these regimens can yield resection rates up to 68% and 36%, in borderline resectable and locally advanced PDAC, respectively 2.
Comparison of mFOLFIRINOX and Gemcitabine/Abraxane
- A study comparing the two regimens found that mFOLFIRINOX was associated with higher rates of RECIST partial response and subsequent pancreatectomy than Gemcitabine/Abraxane, but the overall survival associated with these regimens was similar 3.
- The study also found that patients treated with mFOLFIRINOX were generally younger and had better performance status, but more invasive tumors than patients who received Gemcitabine/Abraxane 3.
Adjuvant Chemotherapy after Neoadjuvant FOLFIRINOX
- A retrospective cohort study found that adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant FOLFIRINOX treatment was associated with improved survival only in patients with pathology-proven node-positive disease 4.
- The study found no survival difference between patients who received adjuvant chemotherapy and those who did not, with a median overall survival of 29 months in both groups 4.
Current Recommendations
- Adjuvant chemotherapy with mFOLFIRINOX remains the standard of care in fit patients with resected pancreatic cancer, and limited high-level evidence supports the use of neoadjuvant therapy in upfront resectable pancreatic cancer 5, 6.
- Neoadjuvant treatment concepts are promising but need to be further evaluated in prospective studies 6.