Phase I Study Of Chemoradiotherapy Using Gemcitabine Plus Nab-Paclitaxel For Unresectable Locally Advanced Pancreatic Cancer.

523 Background: Gemcitabine plus nab-paclitaxel (GnP) treatment is recommended for metastatic pancreatic adenocarcinoma (PDAC), and has been widely spread in our clinics. However, the usefulness for the patients with locally advanced PDAC is still controversial. We designed the phase I study to assess the toxicity and decide the recommended dose based on dose-limiting toxicity (DLT) of concurrent chemoradiotherapy using GnP for unresectable locally advanced (UR-LA) PDAC. Methods: UR-LA PDAC patients were enrolled in this clinical trial. The patients received the GnP on days 1, 8 and 15 every 28 days, and the cycles were repeated until PD. The patients were scheduled to receive gemcitabine (mg/m2) and nab-paclitaxel (mg/m2) at 5 dose levels: 400/75 (level 0), 600/75 (level 1), 600/100 (level 2), 800/100 (level 3) and 800/125 (level 4). Radiation therapy was delivered as a total dose of 50.4 Gy in 28 fractions, 1.8Gy per day. DLT was defined as grade 4 leucopenia or neutropenia ≥ 3 days, grade 3 neutropenia with fever ≥ 38℃, grade 3 or 4 thrombopenia, grade 3 non-hematological toxicity and > 14 days delay of treatment. Response and disease control rate, safety, adverse events, PFS and OS were evaluated. Results: Twelve patients were enrolled in this study. Treatment was well tolerated, and every 12 patients completed radiotherapy of 50.4 Gy. Our recommended dose was level 3, gemcitabine 800 mg/m2 and nab-paclitaxel 100 mg/m2. One patient experienced the DLT. The response rate was 41.7% and disease control rate was 75% (PR: 5, SD: 4, PD: 3). Median OS was 9.0 months. Among 12 patients, 6 (50%) patients underwent conversion surgery, and the pathological CR was observed in 2 patients. Conclusions: The concurrent chemoradiotherapy using GnP for UR-LA PDAC can be delivered safely and the high rate of conversion surgery was observed in our clinical trial. Based on this results, we will proceed the phase-II study. Clinical trial information: UMIN000020475.