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475 Background: Pancreatic cancer (PC) is one of the most difficult cancers to treat. Over 90% of cases, they are UR-LAPC or metastatic PC (mPC) at the first time of diagnosis. To prolong survival time, radiation therapy is considered to be promising with strong local control. Some papers reported that RT with 5-FU is effective to LAPC, but they are far from standard regimen. Gemcitabine (Gem) has enhancing effect of sensibility to RT. Gem and nab-paclitaxel (G+NP) showed priority compared with Gem monotherapy in mPC patients with Phase III study. So, we performed Phase I study to decide recommended dose of G+NP when we administer for concurrent CRT in URPC patients. Methods: From Aug 2013, we have registered patients who were examined as UR-LAPC because of cancer invasion to major artery. Dose of G+NP are classified by each level. At Level 1, Gem 600mg/m2 and NP 50mg/m2. At Level 2, Gem 600mg/m2 and NP 75mg/m2. At Level 3, Gem 600mg/m2 and NP 100mg/m2. At each level, patients accepted RT (50.4Gy/28fr). During performing RT period, we prescribed G + NP weekly. So, G+NP are prescribed 4-5 times if pts accomplish the study.We evaluate effectiveness and side effect of the regimen, and try to decide maximum tolerated dose. Results: Until July 2014, 14 pts (11 males and 3 females) have been registered in this trial. 6 cases were performed at Level 1, 7cases at Level 2, 1 cases at Level 3. 13 cases accomplish the prescription. 1 case at Level 1 dropped out because the patient suffered liver abscess. Effectiveness of the regimen is as follows; 4cases are PD (progressive disease), 6cases are SD (stable disease), and 2cases are PR (partial response). Conclusions: Now we prescribe the regimen at Level 3. We have not yet decided MDT. But, CRT with G + NP may be promising regimen for LAPC. When we accumulate more cases, and decide MDT, we will report later. Clinical trial information: UMIN000012254.

423 Background: A randomized phase 2 trial was conducted in order to investigate the most effective administration method of antithrombin (AT) products in patients with disseminated intravascular coagulation (DIC) associated with sepsis during treatment for advanced pancreatic and biliary cancer (aPBC). Methods: Diagnoses of DIC were made according to the criteria of acute DIC of the Japan Association of acute Medicine. We examined 42 patients who were diagnosed with septic DIC and showed a level of AT lower than 70% during treatment for aPBC. The patients were evenly divided into two groups: Group A (21 patients) received continuous infusions of AT products 1500 IU per day for three days, and the group B (21 patients) received intermittent infusions of AT products 500 IU×3 per day for three days. Changes in the coagulation parameters, inflammatory markers, SIRS positive scores, and DIC scores that occurred during treatment were compared between the two groups. Furthermore, the survival outcomes of the patients were evaluated using the Kaplan-Meier method. Results: Before treatment, there were no significant differences between the two groups with respect to their backgrounds. During treatment, statistically significant differences were seen in the platelet counts, D-dimer test results, Fibrinogen levels, and CRP levels between the two groups. However, no differences were observed between the two groups regarding the changes of AT activity levels, SIRS positive scores, and DIC scores. No statistically significant differences were noted between the groups in regards to their survival outcomes (28 day survival rates: 85.7% versus 71.4%, p=0.283). A multivariate analysis indicated that baseline AT activity levels were the sole factor associated with the 28-day survival rates. The survival outcomes didn’t depend on the administration method of AT products. Conclusions: In this trial, we found that baseline AT activity levels were the sole factor associated with the 28-day survival rates. There was no difference in therapeutic effects between the continuous and intermittent infusions of AT products. Clinical trial information: UMIN 000015105.

e15194 Background: For pancreatic cancer (PC), the regimens which have been approved in Japan are gemcitabine(G), S-1(S), erlotinib combined with G(GE),and GS. And we have conducted chemoradiation ...

301 Background: Treatment options for patients with metastatic pancreatic cancer are still limited. Recently, new strategies to prolong disease control are reported. We conducted phase I/II trial of GEM+CPT-11 combination chemotherapy for MPC to evaluate the effectiveness and safety. Methods: As phase I study, traditional 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose. Four escalating dose levels of GEM/CPT-11 (800/60 mg/m2, 1000/60 mg/m2, 1000/80 mg/m2, and 1000/100 mg/m2) were studied. As results of this investigation, the recommended phase II dose was GEM 1000 mg/m2 and CPT-11 100 mg/m2, biweekly. Phase II eligibility included naïve MPC, PS0-2, Pathological diagnosis, no refractory ascites and pleural effusion, and adequate organ function. Primary endpoint was overall survival. Results: Eighteen patients were entered phase I study. The DLTs were anorexia, and nausea/vomiting. Severe neutropenia was rare. MTDs were determined GEM 1000 and CPT-11 100 mg/m2. After that, we investigated phase II trial in 40 patients. There were 6 partial response, 14 stable disease, 18 progressive disease and 2 in-evaluable. Response rate was 16%. The median overall survival was 7.5 months; progressive disease 4.0 months. Grade 3 to 4 toxicity included neutropenia (7%), anemia (7%), diarrhea (7%), ALT elevation (10%), pneumonitis(7%). There was no treatment-related death. Conclusions: This combination chemotherapy is not effective as first-line chemotherapy for metastatic pancreatic cancer. But this is safe and generally well tolerated. This chemotherapy could be effective of salvage chemotherapy with low toxicity after standard chemotherapy such as FOLFIRINOX.

331 Background: Pancreatic cancer(PC) patients(pts) with peritoneal dissemination are poor prognosis. This retrospective study evaluated the prognosis of Gemcitabine(GEM)-based current chemotherapy(G), GEM plus S-1 combination therapy(GS) and single agent of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination. Methods: This is a retrospective study of PC pts with ascites or peritoneal nodules in the CT or US image who underwent chemotherapy between 2002 and 2011. We collected data on age, sex, Performance Status(PS), tumor location, other metastasis location, status of peritoneal dissemination, CA19-9, CEA, albumin, CRP. We classified 1st line chemotherapy regimen in G, GS and S-1, and we evaluated 1-year survival rate, progression free survival(PFS), overall survival(OS) for the 3 regimens. Results: A total of 81 pts were included. Median age were 64 (38-78), males 50%, PS 0-1 89%. The number of pts treated with G, GS, S-1 was 54, 14, 13. The 1-year survival rate of G, GS and S-1 were 20.3%, 28.5% and 53.8%. The median PFS were 106 days, 84 days and 88 days, respectively. The median OS were 196 days, 154 days, 359 days, respectively. The 1-year survival rate of S-1 was significantly better than that of G (p=0.01). Median PFS and median OS of S-1 didn’t demonstrate the superiority compared with that of G (p=0.40, p=0.08). Conclusions: We suggest the selection of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination might be effective and we need further investigation.

261 Background: We conducted chemoradiotherapy of gemcitabine plus S-1, key drugs for pancreatic cancer. Methods: Patients were eligible for the study if they had received a histopathological diagnosis of locally advanced pancreatic cancer and were diagnosed as unresectable by multiple clinicians including surgeons due to main arterial invasions and more. Radiation (RT) was perfomed for twenty-eight days continuously except Saturday, Sunday and National holiday in 1.8Gy once daily (total 50.4Gy). PTV was defined as GTV plus 10-15mm. Prophylactic irradiation to regional lymph nodes was not performed. Administration level of the anti-cancer drugs was referred to the following table. Results: A total of fifteen cases were enrolled to the phase I study from February, 2006 through May, 2007. RT was achieved in 13 of 15 cases (87%). Two cases of DLT occurred in level 2 (two cases of emesis) while three did in level 3 (one case of emesis and two of neutropenia of grade 4). We decided level 3 as MTD and level 2 as recommended dose. The overall response rate (more than PR) was 33.3% (5 in 15 cases) and tumor-control (more than SD) was achieved in 13 of 15 cases (87%). The one-year and two-year survival rate was 86.7% and 44.4%, respectively. Conclusions: We conducted the phase 1 study of chemoradiotherapy with two key drugs of pancreatic cancer and achieved the recommended dose in this phase I study. Ongoing study We have already finished the enrollment of 110 cases for a phase II randomized allocated study, comparing the chemoradiotherapy of administration dose decided in this phase 1 study with the combination therapy of gemcitabine plus S-1. Now we are carefully following the patients to compare two-year survival rate as a primary endpoint in phase II study. Clinical trial information: NCT01430052.