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DESCRIPTIONDosing of 5-fluorouracil (5-FU) in cancer patients to a predetermined area under the curve (AUC) target has been proposed as a method to reduce variability in systemic exposure to 5-FU, reduce toxicity, and improve tumor response. Accurate AUC determination relies on sampling at a pharmacokinetically appropriate time, as well as on an accurate method of 5-FU laboratory measurement. Available measurement methods are complex and require the expertise to develop an in-house assay, making them less amenable to routine clinical laboratory settings. One commercially available alternative is Myriad Genetics’ OnDose™, a diagnostic test that is designed to measure colorectal cancer patients’ exposure to 5-FU, to help oncologists adjust and optimize 5-FU dosing and improve patient outcomes.
5-Fluorouracil is a widely used antineoplastic chemotherapy drug with a narrow therapeutic index; doses recommended for effectiveness are often limited by hematologic and gastrointestinal toxicity. Moreover, patients administered the same fixed dose, continuous infusion regimen of 5-FU have wide intra- and inter-patient variability in systemic drug exposure as measured by plasma concentration or, more accurately, by area under the curve techniques (AUC). AUC is a measure of the systemic drug exposure in an individual over a defined period of time.
In general, the incidence of grade 3 to 4 toxicity (mainly neutropenia, diarrhea, mucositis, and hand-foot syndrome) increases with higher systemic exposure to 5-FU. Several studies have also reported statistically significant positive associations between 5-FU exposure and tumor response. In current practice, however, 5-FU dose is reduced when symptoms of severe toxicity appear, but seldom increased to promote efficacy.
Based on known 5-FU pharmacology, it is possible to determine a sampling scheme for AUC determination and to optimize an AUC target and dose adjustment algorithm for a particular 5-FU chemotherapy regimen and patient population. For each AUC value or range, the algorithm defines the dose adjustment during the next chemotherapy cycle most likely to achieve the target AUC without overshooting and causing severe toxicity.
In clinical research studies, 5-FU blood plasma levels have most recently been determined by high-performance liquid chromatography or liquid chromatography coupled with tandem mass spectrometry.
Both methods require the expertise to develop an in-house assay and may be less amenable to routine clinical laboratory settings. One commercially available alternative is Myriad Genetics OnDose™, a diagnostic test that is designed to measure colorectal cancer patients' exposure to 5-FU to help oncologists adjust and optimize 5-FU dosing.
The OnDose™ test is offered by Myriad Genetics as a laboratory-developed test. Other clinical laboratories may offer in-house assays to measure 5-FU AUC. Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratories offering such tests as a clinical service must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA) and must be licensed by CLIA for high-complexity testing. Myriad Genetics is a CLIA-licensed laboratory.
POLICYOnDose™ testing or other types of assays for determining 5-fluorouracil area under the curve in order to adjust 5-FU dose for colorectal cancer patients or other cancer patients is considered investigational.
POLICY GUIDELINESInvestigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY07/21/2011: Approved by Medical Policy Advisory Committee.
04/26/2012: Policy reviewed; no changes.
07/19/2013: Policy reviewed; no changes to policy statement. Added HCPCS code S3722 to the Code Reference section.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.68
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.