The use of non invasive methods to predict drug handling and toxicity of Irinotecan

Interventions: Standard treatment of FOLFIRI or FOLFIRI-Avastin regimen for the period of 8 weeks
The Irinotecan will be given over 90 minutes followed by Leucovorin given intravenously over 2 hours and immediately followed by Avastin given over 1 hour if the doctor decides to combine it with FOLFIRI. 5FU will be given intravenously by rapid injection and then 5FU will be given over 46 hrs through a pump connected to the PORT/PICC. Patient will be educated about the care of the PICC or PORT and the pump. The pump will be disconnected at the end of the 46 hours performed at patient home.
Total duration of the study 4 years
Primary outcome(s): Response assessment in the first 4 courses of treatment
using computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and/or positron emission tomography (PET) and/or X-Ray and clinical examination.[8 weeks];Correlations between functional imaging and PK
and between functional imaging and Toxicity
Associations will be assessed to examine the strength and direction of the linear relationship between HFI with PK and toxicity parameters. The Pearson correlation coefficient (for normally distributed variables) or nonparametric Spearman rank correlation (for any non-normally distributed variables) will be calculated with the correlation (r2) and p-value reported. Linear regression models to predict PK parameters from HFI parameters will be fitted to estimate the relationship between pairs of parameters identified as having a significant correlation coefficient. Logistic regression will be used to assess whether HFI parameters can predict presence or absence of grade delayed diarrhoea and neutropenia.[In the 4th year of the project];Correlations of genetic factors, with PK, toxicity and response
SNP genotypes will be assessed for deviations from Hardy-Weinberg equilibrium. Fisher’s exact test or Pearson’s chi-square test will be used, as appropriate, to assess the association between SNP genotypes with toxicity and objective response in 2 degree of freedom tests. Linear and logistic regressions will be used to assess the relationship between the number of minor alleles at each SNP with pharmacokinetic, toxicity and response parameters, as appropriate, in 1 degree of freedom tests.[In the 4th year of the project]
Study Design: Purpose: Natural history;Duration: Longitudinal;Selection: Defined population;Timing: Prospective