Pharmacometabonomic profiling as a predictor of toxicity in patients with inoperable colorectal cancer treated with capecitabine.

Abstract

Endogenous metabolic profiles have been shown to predict the fate and toxicity of drugs such as acetaminophen in healthy individuals. However, the clinical utility of metabonomics in oncology remains to be defined. We aimed to evaluate the effect of pretreatment serum metabolic profiles generated by (1)H NMR spectroscopy on toxicity in patients with inoperable colorectal cancer receiving single agent capecitabine. Serum was collected from 54 patients with a diagnosis of locally advanced or metastatic colorectal cancer prior to treatment with single agent capecitabine. (1)H NMR spectroscopy was used to generate metabolic profile data for each patient. Toxicities were graded according to National Cancer Institute Common Toxicity Criteria version 2.0. Higher levels of low-density lipoprotein-derived lipids, including polyunsaturated fatty acids and choline phospholipids predicted for higher grade toxicity over the treatment period. Statistical analyses revealed a "pharmacometabonomic" lipid profile that correlated with severity of toxicity. This study suggests that metabolic profiles can delineate subpopulations susceptible to adverse events and have a potential role in the assessment of treatment viability for cancer patients prior to commencing chemotherapy.