September 2014, Vol 3, No 6

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Pharmacokinetic-Guided Dosing of 5-FU Shown Cost-Effective


Using a commercially available assay to guide dosing of 5-fluorouracil (5-FU) for the treatment of metastatic colorectal cancer is cost-effective based on a survival advantage over dosing based on body surface area, according to an analysis conducted by Daniel Goldstein, MD.

Currently, the standard treatment for metastatic colorectal cancer is a regimen of 5-5-FU given with leucovorin and oxiliplatin (FOLFOX). Dosing is typically calculated by body surface area, but this method of dosing may result in substantial inter-individual variability in drug exposure, frequently resulting in high toxicity levels, he said.

Development of an immunoassay for 5-FU now allows pharmacokinetic (PK)-guided dose adjustments of FOLFOX to individualize chemotherapy treatments. The results of 2 separate studies showed that this method improves overall survival (OS) and decreases toxicity versus body surface area-guided dosing in patients with metastatic colorectal cancer.

“The issue of personalizing the dosing of 5-FU has been around for quite some time,” he said. “This is probably 1 of the first tests that has shown to be validated and have clinical utility, but it’s in its infancy.”

Recognition of the benefits of PK-guided dosing led Goldstein to compare the cost-effectiveness of PK FOLFOX to traditional body surface area FOLFOX in patients with metastatic colorectal cancer. Dose adjustments of 5-FU based on PK can be made using an immunoassay for 5-FU, said Goldstein, a hematology and medical oncology fellow at Emory University, Atlanta, although he acknowledged that presently, PK-guided dosing is not being extensively used. “It is not used so much in the U.S. at the moment,” he said. “When you use the PK test to guide the dosing, you do get improved overall survival and decreased toxicity. The test is only $400 to $500, so we did a cost-effectiveness analysis to see if this extra spending on the test has value.”

The cost-effectiveness of PK FOLFOX was compared with body surface area FOLFOX, through the use of a Markov model. Published data on progression-free survival (PFS) and OS were used to estimate progression and mortality risk.

Costs for chemotherapy administration and management of adverse events were established based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on the Medicare and Medicaid prices. All costs were calculated averages of 2013 price ranges in US dollars.

Calculated into the cost estimation were drug costs (Medicare and Medicaid Services average sales price), administration costs, and costs for grade 3/4 adverse events. The cost of the PK test was assumed to be $400.

Primary outcomes were measured in incremental cost per quality-adjusted life-year (QALY) gained. PK FOLFOX was found to provide 2.03 additional QALYs at a cost of $50,205, compared with body surface area FOLFOX with 1.46 QALYs at a cost of $37,173. The incremental cost-effectiveness ratio (ICER) was $22,696/QALY. This ICER was well below the $50,000 willingness to pay threshold in all one-way sensitivity analyses. In probabilistic sensitivity analyses, 99% and 95% had ICERs below $42,000/QALY and $34,000/QALY, respectively.

The main cost driver for PK FOLFOX was the $400 PK test that was used for 4 cycles to establish optimal doses, said Goldstein. The main driver of benefit was improved PFS and OS.

“Given the cost-effectiveness profile and OS advantage with PK FOLFOX, it should be evaluated further in comparative effectiveness studies,” he noted.

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