Background: Chemoradiation (CRT) is used in unresectable pancreatic cancer (PC) to convert patients to a resectable state. Those who go to surgery can have a similar survival as those initially deemed resectable, with a mOS of 8.2-9 mo. We recently reported a prospective phase II trial of our synergistic regimen (GTX) for patients with metastatic PC with a mOS of 14.7 mo. Methods: 35 patients with ECOG PS 0-2 and completely unresectable advanced PC (localized to the pancreas, small bowel, stomach and/or encasing at least 2 vessels such as the SMA, CA, HA, PV, or SMV) were treated with GTX: Capecitabine (Xeloda) PO 1500mg/m² divided into 2 doses daily on days 1-14, gemcitabine 750mg/m² IV given over 75 min on days 4 & 11, docetaxel 30mg/m² IV infusion over 30 minutes preceded by dexamethasone 10mg IV/PO on days 4 & 11, in a 21 day cycle. 3 cycles were given before evaluation. If eligible, a patient was allowed to proceed to surgery without radiation. Otherwise, starting on week 12, 5040 cGy of conformal radiation was given over 5-6 weeks (Mon-Fri) with weekly gemcitabine 250-300mg/m² IV infusion over 30 min. No adjuvant treatment was given on protocol. Primary objective was conversion rate to operable status, and secondary objectives included RR (based upon RECIST), OS, and PFS. Results: Duration of neoadjuvant chemotherapy was 9 weeks and 0% showed POD during this time. 20 of 35 patients (57%) became eligible for surgery. Of all 35 patients, there was a 49% rate of negative margins at surgery (in 85% of those patients who underwent surgery). 23 patients (66%) underwent CRT, and 11 of them (48%) ultimately went to surgery and had clean margins. Median OS from initiation of chemotherapy for all patients was 17.4 mo and >22 mo if they went to surgery (20/35 pts, 1 alive). PFS of patients who underwent surgery was 13.2 mo. Grade 3/4 toxicities primarily included neutropenia (25%), leukopenia (11%), and diarrhea (6%). No deaths were attributed to GTX. Conclusions: Neoadjuvant GTX +/- radiation with gemcitabine can be used as an effective treatment for patients with truly unresectable PC. Clinical trial information: NCT00869258.