2108 Purpose: This trial has been designed in order to establish potential pharmacokinetic (PK) interaction between Oxaliplatin (Oxa)and Xeloda (Xel) when administrated in combination and to monitor neurological toxicity when Oxa is administered over 6 hours infusion. Treatment schedule: Oxa 130 mg/m2 6 hours perfusion at day 1, Xel 1000 mg/m2 twice daily at day 2 to 15. Treatment repeated every 22 days if > 1000 neutrophiles and > 100 000 platelets and no other G 3–4 non hematological toxicity. PK analysis were performed at day 1 and 15; receptor for IL 6 at day 1. Blood sampling was done - on day 1 (30min before the end of infusion and 1h30min after the end of infusion in order to validate the Pk population model we recently published for Oxa). On day 2, 30min, 1h, 2h and 4h after Xel. Xel, dFdC, dFdU, 5FU and FBAL were monitored by HPLC and GC-MS in order to determine potential metabolic interaction with Oxa. On day 14, 30min, 1h, 2h and 4h after Xel in order to compare adsorption and PK of Xel and metabolites with and without Oxa. Results: Between April 2003, and December 2003, 10 patients with advanced colo-rectal cancer were included, in first line chemotherapy for metastatic disease, 3 males and 7 females, 7 colon cancer and 3 rectum, medium age 56 (46 to 66) : PS 0=7, PS 1=2, PS 2=1; liver involvement in 8 patients (80 %) and lung in 4 patients (40 %); median cycles 4 (1 to 9). Toxicity = 3 pts Grade III diarrhea, 1 heart pain at day 2 of first cycle and 1 unexplained death. No hand-food syndrome was observed in this population. Only mild paresthesia in 2 Pts (20%)after 7 cycles Efficacy : 2 CR, 2 PR and 2 stabilizations. PK and IL6 receptor results will be presented. So far, 2 plasma samples are enough to extrapolate AUC of ultrafilterable Oxa according our model. Pk of Xel and metabolites are currently evaluated and Pk interaction between Oxa and Xel will be analysed. Conclusion: This combination is active, easy to administer and very well tolerated especially without significant neurological toxicity when Oxa is infused over 6 hours. Moreover, 2 blood samples are sufficient to monitor Oxa Pk according to the population Oxa parameters and to consider posology adaptation in further trials. No significant financial relationships to disclose.