Background: The results of a randomized comparison study (N9741) showed that oxaliplatin and infusional fluorouracil (FU) (FOLFOX) was superior to the previous standard of care in the United States, irinotecan and bolus FU (IFL), as first-line therapy for patients with metastatic colon carcinoma. The trade-offs between costs and survival for these two regimens have not been explored.
Methods: A post-hoc, incremental cost-effectiveness (ICE) projection using simulated cohorts of patients starting FOLFOX or IFL was tracked for major clinical events, toxicities, and survival. Recurrence and survival risks were based on clinical trial data. Resource use was projected using observed dose intensity, duration of therapy, delays in therapy, and toxicities Grade > 2 in N9741. The frequency, costs, and consequences of second-line therapy were examined. The time frame was 5 years, and the perspective was that of Medicare as a third-party payer.
Results: Initial treatment with FOLFOX versus IFL had an average incremental cost of dollars 29,523, a survival benefit of 4.4 months, and an ICE of dollars 80,410 per life year (LY), dollars 111,890 per quality-adjusted LY, and dollars 89,080 per progression-free year. By using the 95% confidence interval for the time to progression observed in N9741, the ICE associated with FOLFOX ranged from dollars 121,220 to dollars 59,250 per LY. In the clinical trial, dose delays and skipped doses were frequent. If progression-free patients were treated without delay for the first year or lifetime, then the ICE for FOLFOX increased to dollars 117,910 and dollars 222,200 per LY, respectively. The ICE increased to dollars 84,780 per LY when the model incorporated a revised IFL schedule with lower early toxicity and similar rates of treatment with second-line regimens.
Conclusions: FOLFOX provided substantial benefits that incurred substantial additional costs. The ICE for FOLFOX fell into the upper range of commonly accepted oncology interventions in the context of the United States healthcare system.
(c) 2005 American Cancer Society.