307 Background: Unresectable pancreatic cancer is poorly responsive to conventional therapies. We conducted a phase I/II study to ascertain the recommended dose (RD) of 5-fluorouracil (5-FU) in arterial infusion chemotherapy combined with systemic gemcitabine in unresectable pancreatic cancer and to evaluate the safety and efficacy. Methods: 5-FU was administered through the pancreatic and hepatic arteries via the port system as a 5-hour infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. Gemcitabine was administered in 30-minute intravenous infusion at the same days. In phase I, escalating 5-FU doses for level 1 and 2 was set at 750mg and 1,000mg/m2, respectively. Dose of coadministered gemcitabine (1,000 mg/m2) was fixed. Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed, and RD was estimated in the first cycle. In phase II, more RD patients were added to assess tumor response, toxicity, overall survival and progression-free survival. Results: During the phase I, 7 patients were enrolled. DLT was not observed. One patient dropped out of this study because of insufficient drug distribution via the port system. Assuming RD at 1,000mg/m2 of 5-FU, the phase II enrolled a total of 16 patients (metastatic, 14; local advanced, 2). The tumor response rate was 68.8% (CR 0, PR 11, SD 2, PD 3). The grade 3 toxicities of neutropenia (6%) and thrombocytopenia (6%) were observed. Median overall and progression-survival times (all patients) were 9.8 and 6.2 months, respectively. Conclusions: Arterial infusion 5-FU 1,000mg/m2 combined with full-dose systemic gemcitabine was tolerable and can produce a high response rate with encouraging survival duration for unresectable pancreatic cancer. No significant financial relationships to disclose.
Recombinant human adenovirus‑p53 improves the outcome of mid‑late stage pancreatic cancer via arterial infusion
