3672 Background: The complete resection of macroscopic PC followed by intraoperative IPCH to treat residual microscopic disease enables curing some patients (pts). Methods: Pts with PC from gastrointestinal or other origin underwent complete cytoreductive surgery followed by intraoperative IPCH with a fixed dose of L-OHP (460 mg/m2) and one of the 7 increasing doses of CPT-11 (from 300 to 700 mg/m2). IPCH was performed using an open procedure for 30 min at an IP temperature of 43°C with 2l/m2 of 5% dextrose instillation in a closed continuous circuit. Just before IPCH, pts received systemic IV leucovorin (LV) 20mg/m2 and 5FU 400mg/m2 to maximize the effect of L-OHP and CPT-11. Results: From May 2002 to June 2003, 39 pts were included with: M/F: 13/26; median age: 46y[26–60]; primary tumor was: 20 colorectal,11 appendix pseudomyxoma,3 endocrine tumors,3 mesothelioma, 2 small bowel. The PK of IP L-OHP was not modified by increasing doses of IP CPT-11, and the drug concentration was 17.8 higher in bathed tumor tissue that in non-bathed tissue. The PK of IP CPT-11 showed an exponential decrease in the peritoneal perfusion and a peak of plasma concentration at 30 min. SN-38 was present in peritoneal instillation immediately after the beginning of IPCH. CPT concentration in tumor tissue increased until the step of 400 mg/m2, and then remained stable. It was 16 to 23 higher than in non-bathed tissues. Half of the L-OHP and CPT-11 was absorbed during the procedure. The hospital mortality rate was 2.5% and the non hematological grade 3 to 5 complication rate (abdominal and intraabdominal) was 25%. At the recommended dose of 400mg/m2, 5/6 pts had grade ½ hematological toxicity: 2 anemia, 5 neutropenia, 1 thrombopenia.The hematological toxicity was correlated to the extent of PC (p=0.017) and duration of surgery (p=0.046). Conclusions: This trial demonstrated a dose related exposure and efficient intratumoral penetration of the 2 drugs. The recommended dose of IP CPT-11 was 400 mg/m2, for phase 2. This phase 2 trial is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Aventis Pharmaceutical Co. Aventis Pharamceutical Co. Aventis Pharamceutical Co. Aventis; Sanofi-Synthelabo