P-203 Relationship of myelotoxicity and of gastrointestinal toxicity with the treatment outcome in trials of second-line chemotherapy of patients with metastatic colorectal cancer

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Although some toxicities of molecularly targeted therapies have been shown to predict drug activity, this is unclear for traditional cytotoxic chemotherapy. Various studies, mostly in later lines of metastatic disease, have documented that neutropenia after chemotherapy has a predictive role for the efficacy of chemotherapy in patients with mCRC. In particular, it seems that mild neutropenia is the one that is most often associated with the best outcome. After systematic review and selection of the randomized phase III trials of second-line chemotherapy of patients with mCRC, all those that reported bone marrow (neutropenia, anemia, thrombocytopenia) and gastrointestinal (diarrhea, vomiting) toxicities, mild or severe, were included in the analysis. For each trial, the relationship between the difference in the frequency rates of each of the toxicities between study arms with the difference in PFS was evaluated by Pearson's test (rho), in order to detect a possible correlation between toxicity and outcome. Fourteen studies were selected. The difference in neutropenia rates between the study arms correlated with the difference in PFS (rho = 0.817; p-value 0.004; 10 studies). In particular, the correlation was significant for mild neutropenia (rho = 0.764; p-value 0.004; 12 studies). Similar data, though from a smaller number of studies, were detectable for the other bone marrow toxicities but not for the gastrointestinal ones. Mild to moderate bone marrow toxicity could be a predictor of the efficacy of second-line cytotoxic chemotherapy in patients with mCRC, and therefore it could reflect not only the direct toxicity of the drugs, but also a chemotherapy-related response mechanism.