Key result
Doxorubicin-based chemotherapy significantly increased urinary F2-isoprostanes by 41% to 62% at 1 hour post-treatment (P<0.05), which returned to baseline levels at 24 hours.
Why the study?
Does doxorubicin-based chemotherapy increase urinary biomarkers of oxidative status in newly diagnosed breast cancer patients?
Observational (n=23)
Does doxorubicin-based chemotherapy increase urinary biomarkers of oxidative status in newly diagnosed breast cancer patients?
p-value: p=<0.05
Urinary F2-isoprostanes rapidly increase following doxorubicin administration, serving as valid biomarkers of oxidative assault.
May reflect acute oxidative stress from doxorubicin without altering practice; hypothesis-generating for F2-isoprostanes in cardio-oncology monitoring.
BACKGROUND: We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans. METHODS: The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and 24 hours (T24) after i.v. administration of treatment. Measurements included allantoin and the isoprostanes iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso-iPF(2alpha)-VI along with the prostaglandin 2,3-dinor-iPF(2alpha)-III, a metabolite of iPF(2alpha)-III. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: In all subjects, the levels of the biomarkers increased at T1: allantoin by 22% (P = 0.06), iPF(2alpha)-III by 62% (P < 0.05), iPF(2alpha)-VI by 41% (P < 0.05), 8,12-iso-iPF(2alpha)-VI by 58% (P < 0.05), and 2,3-dinor-iPF(2alpha)-III by 52% (P < 0.05). At T24, the F2-isoprostanes returned to their baseline levels; the levels of allantoin continued to increase, although the T24-T0 difference was not statistically significant. CONCLUSIONS: These results indicate that urinary F2-isoprostanes are valid biomarkers and allantoin is a promising biomarker of oxidative status in humans. IMPACT: The levels of biomarkers change quickly in response to oxidative assault and can be used to monitor oxidative status in humans in response to treatments related either to generation of free radicals (chemotherapy and radiation therapy) or to antioxidants (inborn metabolic diseases and Down syndrome).
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Il’yasova et al. (2010) conducted an observational in Breast cancer (n=23). Doxorubicin-based chemotherapy vs. Baseline (pre-treatment) was evaluated on Urinary levels of allantoin and F2-isoprostanes (p=<0.05). Doxorubicin-based chemotherapy significantly increased urinary F2-isoprostanes by 41% to 62% at 1 hour post-treatment (P<0.05), which returned to baseline levels at 24 hours.
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