Tu1894 Ultrahigh-Throughput Screening Strategies for Identification of Small-Molecule Compounds That Target the Colon Cancer Oncogene KrüPpel-Like Factor 5

Aim: The aim of the present study was to evaluate whether chronomodulated administration of capecitabine would reduce toxicity of the drug in patients with metastatic colorectal cancer. Patients & Methods: 27 patients with advanced colorectal cancer were randomized to receive capecitabine (2500mg/KOF daily) either in standard administration with 50% of the dose in themorning and 50% in the evening separated by 12 hours or as chronomodulated dose-regime with 25% morning-dose and 75% late evening-dose. Treatment was continued until thirteen treatment-cycles were finished or progress of cancer or limitation of therapy due to side effects occurred. Results: Overall, response rates to chemotherapy were similar in both treatment groups (p= 0,296). However, within the group of patients with chronomodulated application of capecitabine, reduction of drug-doses due to side effects was less frequently necessary (14.8 vs. 19.3%, p=0,026) and more patients were able to finish all thirteen chemotherapy-cycles (41.7 vs. 7.1%, p=0,007). While there was no statistically significant difference in the frequency of hand-foot-syndrome in both treatment-arms (51.7 vs. 41.5%, p=0,119) other side effects as nightly nausea, tiredness and sleeplessness were significantly reduced in patients receiving chronomodulated therapy (p=0,035, p=0,001 and 0,009, respectively). Additionally, there was a trend to lower frequency of nausea, diarrhea and stomatitis within this group compared to standard treatment (9.0 vs. 19.5%, 19.1 vs. 25.6%, and 4.5 vs. 8.5%) Conclusion: The chronomodulated capecitabine schedule achieved similar response rate and better tolerability regarding various side effects compared with standard application of the drug in patients with colorectal cancer. This schedule could enable patients to sustain on capecitabine therapy for a longer time-period.