A phase I/II study of induction oxaliplatin, 5FU chemoradiation in patients with locally advanced, unresectable pancreatic cancer

15027 Background: Newly diagnosed locally advanced and unresectable pancreatic cancer has a 5 yr survival rate of less than 5%. Aggressive local therapy may provide the best means of achieving local control and prolonging survival. We administered concomitant chemoRT with Oxaliplatin and continuous infusional (CIV) 5FU to determine the maximum tolerated dose (MTD) in the phase I portion. Methods: Pts with histologically proven locally advanced pancreatic cancer were enrolled in standard Phase I 3+3 fashion to determine MTD. ChemoRT included 5FU 200mg/m2 CIV and Oxaliplatin wkly X5 wks. Radiation dose was 4500cGy in 25 fractions (180cGy/fx/d) over 5 wks followed by a conedown to the tumor and margin for an additional 540cGy x3 (total dose 5040 cGy in 28 fractions) Oxaliplatin was escalated from 30mg/m2 in 10mg intervals up to 60mg/m2. Following chemoRT, unresectable pts were treated with mFOLFOX6 x 6. Results: 15 pts enrolled in the phase I portion, all completed neoadjuvant therapy. Most hematologic toxicities were gr 1 and 2. There was 1episode of gr 4 lymphopenia. The most common non-hematologic toxicities were gr1–2 fatigue, anorexia, nausea and vomiting. Gr 3 non-hematologic toxicities included 4 episodes hyperglycemia, 1 diarrhea, 1 anorexia, 3 nausea/vomiting and 2 hypokalemia. The highest planned dose level for weekly Oxaliplatin was tolerable and the RPTD is 60mg/m2/wk. Of the 15 pts: 2 progressed, 2 were explored but were unresectable, 2 await exploration and 9 were deemed still unresectable and proceeded to consolidation. 7/9 completed the planned 6 cycles. 1 pt was removed from protocol due to extended delay of treatment due to gr 3 neuropathy. 1 pt died due to progressive disease. 21% of planned cycles were delayed due to gr2 or 3 myelosuppression. 1 pt required dose reduction due to fever in setting of gr4 neutropenia but was able to complete treatment at the reduced dose. Conclusions: Combined modality treatment for locally advanced pancreatic cancer with Oxaliplatin, CIV 5FU and radiation is well tolerated at full doses of Oxaliplatin (60mg/m2/wk) and does not produce substantially more toxicity than standard chemoRT to the pancreatic bed. The phase II portion of the trial is ongoing. [Table: see text]