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Feasibility study of combination therapy with S-1 plus irinotecan in patients with EGFR positive KRAS mutation type unresectable colorectal cancer, who had previously received on irinotecan, oxaliplatin and fluoropyrimidine, bevacizumab

ABSTRACT: Interventions: S-1/irinotecan combination therapy Irinotecan 100 mg/m2(day1,15), S-1 80-120mg/day, PO from day1 to day 14 of each 28 day cycle. Primary outcome(s): Progression free survival(PFS) Study Design: Single arm Non-randomized

DISEASE(S): Colorectal Cancer

PROVIDER: 2625128 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Expression data from Irinotecan resistant LoVo cells comapred to parental LoVo cells

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Expression data from Irinotecan resistant LoVo cells comapred to parental LoVo cells

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Project description:Chronotherapy demands that patients are treated at a particular time of the day in order to maximize treatment effects and minimize side effects. Chronotherapy can be personalized by taking into account the patient's circadian rhythm as measured by a repetitive sampling of gene expression over the day. As a proof of concept, the submitted model links circadian gene expression to the diurnal toxicity profile of the cancer drug irinotecan. The model is based on MODEL2109140001; it implements a transcription-translation network model of the core clock and additional genes associated with irinotecan metabolism and links this to a model of the pharmacokinetics and -dynamics (PK-PD) of irinotecan. The submitted model refines network connections of the gene regulatory network and adds a treatment-induced increase in UGT1A1 and a transient increase in the apoptosis rate in response to treatment for the PK-PD part.

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