What is the comparison between FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) and FOLFIRI (Folinic acid, Fluorouracil, Irinotecan)?

From the Guidelines

FOLFOX and FOLFIRI are both effective chemotherapy regimens for colorectal cancer, with similar efficacy but different toxicity profiles, and the choice between them should be individualized based on patient factors and cancer characteristics 1.

Comparison of FOLFOX and FOLFIRI

• Both regimens combine 5-fluorouracil (5-FU) and leucovorin, but FOLFOX includes oxaliplatin, while FOLFIRI includes irinotecan.
• FOLFOX typically causes peripheral neuropathy, which can be long-lasting, along with cold sensitivity, while FOLFIRI more commonly causes diarrhea and alopecia (hair loss) 1.
• The dose of oxaliplatin in FOLFOX is usually 85 mg/m² every 2 weeks, as there is no evidence that higher doses are more effective 1.
• Both regimens are typically administered every 2 weeks through an infusion port, with 5-FU given as both a bolus and continuous infusion over 46-48 hours.

Treatment Considerations

• The selection between FOLFOX and FOLFIRI should be based on patient factors, such as comorbidities, and cancer characteristics, such as the presence of metastases 1.
• Many patients receive both regimens sequentially during their treatment course.
• Combination chemotherapy with FOLFOX or FOLFIRI provides higher response rates, longer progression-free survival, and better survival than 5-FU/LV alone 1.
• The exposure to all three cytotoxics (fluoropyrimidines, oxaliplatin, and irinotecan) in various sequences may result in the longest survival 1.

From the FDA Drug Label

The results reported below compared the efficacy of oxaliplatin with fluorouracil/leucovorin and oxaliplatin with irinotecan to an approved control regimen of irinotecan with fluorouracil/leucovorin in 795 concurrently randomized patients previously untreated for locally advanced or metastatic colorectal cancer.

Patients who received oxaliplatin with fluorouracil/leucovorin had a significantly longer time to tumor progression based on investigator assessment, longer OS, and a significantly higher confirmed response rate based on investigator assessment compared to patients who received irinotecan with fluorouracil/leucovorin

The comparison between FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) and FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) is as follows:

• Efficacy: FOLFOX has a significantly longer time to tumor progression, longer overall survival, and a higher confirmed response rate compared to FOLFIRI.
• Key outcomes:
  • Overall Survival (OS): FOLFOX has a median survival of 19.4 months, while FOLFIRI has a median survival of 14.6 months.
  • Time to Tumor Progression (TTP): FOLFOX has a median TTP of 8.7 months, while FOLFIRI has a median TTP of 6.9 months.
  • Response Rate: FOLFOX has a response rate of 45.2%, while FOLFIRI has a response rate of 32.5%. 2

From the Research

Comparison of FOLFOX and FOLFIRI

• FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) and FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) are two common chemotherapy regimens used in the treatment of metastatic colorectal cancer 3, 4.
• Both regimens have been shown to be effective in improving outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with metastatic colorectal cancer 3, 4.
• The choice between FOLFOX and FOLFIRI depends on individual patient factors, including treatment goals, efficacy, and tolerability of each regimen 3.
• FOLFOX has been shown to have a higher response rate compared to FOLFIRI, particularly in patients with wild-type KRAS tumors 4.
• However, FOLFIRI has been shown to be effective in patients who are refractory to FOLFOX, and vice versa 4, 5.
• A simplified FOLFOXIRI regimen, which combines irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin, has been shown to have promising antitumor activity and manageable toxic effects 6.
• Population pharmacokinetic studies have been conducted to optimize the FOLFIRINOX regimen, which combines irinotecan, oxaliplatin, and fluorouracil, to improve patient outcomes 7.

Efficacy and Safety

• FOLFOX and FOLFIRI have been shown to have similar efficacy in terms of overall survival, but FOLFOX has been shown to have a higher response rate 4.
• The safety profiles of FOLFOX and FOLFIRI are similar, with common toxicities including neutropenia, diarrhea, and peripheral neuropathy 4, 6.
• The use of anti-EGFR agents, such as cetuximab, in combination with FOLFOX or FOLFIRI has been shown to improve outcomes in patients with wild-type KRAS tumors 3.

Treatment Decisions

• The choice between FOLFOX and FOLFIRI should be based on individual patient factors, including treatment goals, efficacy, and tolerability of each regimen 3.
• Patients with metastases confined to the liver may be considered for surgical resection, and treatment regimens with high response rates, such as FOLFOX, may be preferred 3.
• Patients who are not surgical candidates may be considered for a sequential single-agent strategy or an intermittent approach, with combination therapy followed by maintenance 3.