COST-EFFECTIVENESS OF PHARMACOKINETIC DOSING OF 5-FLUOROURACIL IN METASTATIC COLORECTAL CANCER IN THE UNITED KINGDOM

Dosing of chemotherapy regimens using 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer (mCRC) is based on body surface area (BSA), which has been shown to yield suboptimal plasma 5-FU levels. Pharmacokinetic (PK) monitoring of 5-FU shows promise in terms of optimal dosing, but its cost-effectiveness is unknown. This study performs a cost-effectiveness analysis of PK dosing versus BSA dosing of 5-FU among patients with mCRC in the UK. A decision tree model was used to perform a counterfactual simulation of the cost-effectiveness of PK versus BSA dosing of 5-FU in standard chemotherapy regimens for mCRC in the UK population. All patients were assumed to receive first-line therapy for 6 or 12 cycles or until progression, after which they received standard post-first-line chemotherapy and subsequent palliative care until death. Costs were estimated from the perspective of the national health system as payer, were drawn from the literature and publically available national unit cost estimates. Effectiveness was quality adjusted life years (QALY), with utilities estimated from the literature. Discounting was performed at 3% per year. Incremental cost-effectiveness ratios comparing PK to BSA dosing were computed for the six most common chemotherapy regimens that utilize 5-FU. The average ICER across all regimens and weighted by their current distribution was £7,336 per incremental QALY gained. The ICER for lifetime discounted incremental cost per incremental QALY for PK versus BSA dosing was £3,467 for a FOLFOX4 regimen, £3,594 for a FOLFOX6 regimen, £23,428 for FOLFIRI, £3,508 for FOLFOX6 + bevacizumab, £21,874 for FOLFIRI + bevacizumab, and £28,862 for a 5-FU + leucovorin chemotherapy regimen. PK dose management of 5-FU based chemotherapy regimens for patients with mCRC appears cost-effective from a UK national payer perspective. Cost-effectiveness was driven in part by better efficacy and reduced adverse events.