Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis

Background/Aims: We conducted a phase I trial of IP oxaliplatin and paclitaxel with IV paclitaxel and bevacizumab in patients with peritoneal carcinomatosis. Methodology: Patients received IV bevacizumab (2.5mg/kg) over 1 hour (day 1), then IV paclitaxel (110mg/m ²) 24-hr-infusion (day 1) and IP oxaliplatin (25-40mg/m ²) (day 2), and IP paclitaxel (30-60mg/m ²) (day 8 from cycle 2 onwards). A "3+3" design was used. Results: Nineteen patients were treated (median age 60 years; 10 women, 9 men; median number of prior therapies 3). Primary tumors were colorectal (n=9), signet ring carcinoma (n=2), gastric (n=2), ovarian (n=2) and others (n=4). The maximum tolerated doses (MTD) of IP oxaliplatin and IP paclitaxel were 25mg/m ² and 60mg/ m ², respectively. Nine (47%) patients reported no toxicities >grade 2. Two patients receiving IP oxaliplatin 40mg/m ² and IP paclitaxel 60mg/m ² had dose limiting toxicities (DLT) of grade 3 diarrhea/dehydration and febrile neutropenia. Toxicities included abdominal pain (n=14), nausea (n=10) and constipation (n=7). Of 12 patients restaged at 2 months, 7 (58%) had stable disease (SD) including 2 (17%) who had SD for >4 months. Conclusions: IP paclitaxel and IP oxaliplatin can be given safely at 60mg/m ² and 25mg/m ², respectively.