Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose‐limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom‐relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m(2) respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0–22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1‐year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3–4 haematological toxicities developed in 35 of 46 patients, whereas non‐haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.