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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.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

04/26/2012: Policy reviewed; no changes.

Non-Covered Codes

This is not an all-inclusive list of non-covered procedure codes.

All codes billed for this procedure are considered investigational and not eligible for coverage. 

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