Aims. Severe gastrointestinal (GI) toxicity following 5-FU-based chemotherapy is highly prevalent and negatively affects therapy. We have previously identified that TLR2 and TNF genetic markers together with cancer type predict severe GI toxicity risk1. The aim of this study was to validate these findings in a larger independent cohort.
Methods. Participants who previously received 5-FU-based treatment for mixed cancers were recruited and immune response genetics determined by custom multiplex analysis1. GI toxicity grade (0 to 3 using the National Cancer Institute’s CTCAE v5, where severe toxicity was assigned if grade 3 symptoms were recorded or if there was a need for treatment cessation or reduction), demographics, and treatment parameters were mined from clinical records. General linear models based on lowest Akaike Information Criteria score determined direct relationships.
Results. The GI toxicity grades of the 155 participants were: 14% - 0, 43% - 1, 24% - 2 and 19% - 3.The final model comparing grades 0, 1 and 2 to grade 3 revealed an association between severe GI toxicity and cancer type (colorectal and gastric, P = 0.003). The final model comparing grades 0 and 1 to grade 3 revealed associations between severe GI toxicity and cancer type (colorectal and gastric, P = 0.02) and capecitabine chemotherapy (P = 0.04).
Conclusions. This validation study did not confirm the previously identified impact of TLR2 and TNF genetic variability on severe GI toxicity risk. However, it was able confirm cancer type, and capecitabine chemotherapy in a subgroup of participants, were significant predictors. In comparison to the pilot, this study cohort included a higher percentage of participants with breast cancer and inclusion of a second study site, hence, further subset analysis will be undertaken to investigate these differences more fully.