Pharmacometabonomic Profiling as a Predictor of Toxicity in Patients with Inoperable Colorectal Cancer Treated with Capecitabine

Abstract

Purpose: 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

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

“…Backshall et al [84] used 600 MHz 1 H NMR to show that high pre-treatment serum levels of low-density lipoprotein-derived lipids, including polyunsaturated fatty acids and choline phospholipids, were predictive of greater toxicity, in 54 patients with locally advanced or metastatic colorectal cancer being treated with capecitabine. Although the authors recommended validation by repetition in a larger cohort, this is an important result, as capecitabine toxicity is not only a significant issue for patients' quality of life, it also limits the drug dose range available, and may thereby diminish the likelihood of patient cure.…”

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

“…Finally, it should be noted that there are many human diseases such as childhood autism, childhood hyperactivity and Parkinson's Disease that are associated either with elevated para--cresol levels, or decreased S/G ratios after the dosing of paracetamol, implying impaired sulphation and altered microbiomes in these disease states. Ji et al [43] and Abo et al [44] prediction of sertraline and placebo responses in patients with MDD Kaddurah--Daouk et al, [17,45] Zhu et al [46] prediction of efficacy of anti--psychotics Condray et al [47] prediction of response to aspirin Lewis et al [48] and Ellero--Simatos et al [49] prediction of adverse events prediction of weight gain in breast cancer patients undergoing chemotherapy Keun et al [50] prediction of toxicity in patients with inoperable colorectal cancer treated with Capecitabine Backshall et al [51] prediction of toxicity of paracetamol / acetaminophen ('early--onset pharmacometabonomics') Winnike et al [52] predictive metabonomics prediction of future impaired glucose tolerance or Type--2 diabetes onset Wang--Sattler et al [53] Table 1. An overview of the human pharmacometabonomics and predictive metabonomics studies reported in the literature to late 2014.…”

“…Moving from efficacy prediction to toxicity prediction, the group of Keun have also shown that the analysis of pre--dose serum from cancer patients can predict toxicity when treated with capecitabine. [51] The study included 54 patients with locally advanced or metastatic colorectal cancer. Toxicities were assessed using the National Cancer Institute Common Toxicity Criteria v2.0.…”

The emergent role of metabolic phenotyping in dynamic patient stratification

“…In the oncology field, there has been success in using the approach based on NMR spectra of serum for prediction of toxicity in 54 patients with inoperable colorectal cancer who were treated with capecitabine [12] and using MAS-NMR of tumor tissue samples, it was possible to identify profiles that enabled colorectal cancer staging and prognosis [13].…”