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Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC)., Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity., Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy., Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background/aims: Hypofractionated radiotherapy can shorten the irradiation period and allow systemic chemotherapy with full-dose gemcitabine to be started earlier. The purpose of this study was to determine the feasible dose of hypofractionated radiotherapy that could be followed by full-dose gemcitabine in patients with locally advanced pancreatic cancer., Methodology: Nine patients with unresectable locally advanced pancreatic cancer were enrolled in this study. Three patients received radiotherapy at 45Gy in 15 fractions (level 1) and six at 40 Gy in 8 fractions (level 2). Systemic chemotherapy with gemcitabine was started 3 months after the start of irradiation and was administered as a 30-minute intravenous infusion of a dose of 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle., Results: No patients experienced dose-limiting toxicity at either level of radiotherapy. Gemcitabine was started in two of the three patients treated at the level 1 on schedule. At level 2, grade 3 nausea, vomiting and anorexia was observed in all 6 patients, and gemcitabine could not be started on schedule in 4 of the 6 patients. Two (22%) of the 9 patients achieved a partial response. The median time to progression was 5.8 months and the median overall survival time was 9.5 months., Conclusions: Hypofractionated radiotherapy with 40 Gy in 8 fractions was not feasible in patients with locally advanced pancreatic cancer.

Objective: The purpose of this study was to determine the feasible dose of gemcitabine when administered as a fixed dose rate infusion (10 mg/m(2)/min) on a weekly schedule to Japanese patients with unresectable advanced pancreatic cancer., Methods: Patients were required to have histologically or cytologically proven locally advanced or metastatic pancreatic cancer for which they had received no previous chemotherapy. Gemcitabine was administered intravenously weekly for three consecutive weeks every 4 weeks. Patients at three dose levels were scheduled to receive escalating doses of gemcitabine: 1000 mg/m(2) over 100 min (Level 1), 1200 mg/m(2) over 120 min (Level 2) and 1500 mg/m(2) over 150 min (Level 3)., Results: A total of 16 patients were enrolled in this study between December 2003 and September 2004. Maximum-tolerated dose was not reached during the first course. Dose-limiting toxicity was Grade 4 neutropenia. Grade 3 or 4 neutropenia was observed at Level 3 in all six patients in the first course, and administration of gemcitabine on Day 8 or 15 was skipped in all six patients. Non-hematologic toxicity was mild and the most common symptoms were anorexia, nausea and vomiting. Partial response was achieved in 1 of the 17 patients (7%). Median overall survival was 7.3 months., Conclusions: Gemcitabine administered at a rate of 10 mg/m(2)/min was tolerated up to 1500 mg/m(2), but 1200 mg/m(2) represented a more appropriate recommended dose in further studies owing to neutropenia in Japanese patients with advanced pancreatic cancer.

Background and Aim: A previous randomized trial showed gemcitabine was superior to 5-fluorouracil in overall patient survival. However, the incremental improvement in survival was minimal. It is 2.5 years since gemcitabine has become available for the treatment of pancreatic cancer in clinical practice in Japan. The current study was conducted to examine whether treatment outcomes have changed since the introduction of gemcitabine therapy., Methods: Ninety-one consecutive patients with metastatic pancreatic cancer treated with systemic chemotherapy at the National Cancer Center Hospital East were surveyed. Patients admitted before April 2001 received 5-fluorouracil, and those admitted subsequently received gemcitabine. The patients were divided into the gemcitabine group (n = 50) and the non-gemcitabine group (n = 41), and these groups were compared for five outcomes, objective response rate, non-progressive disease rate, carbohydrate antigen (CA)19-9 response rate, actual survival time, and difference between estimated and observed survivals. The estimated survival time was determined using the prognostic index reported in the previous study., Results: Except for the objective response rate, the four other outcomes in the gemcitabine group were significantly superior to those in the non-gemcitabine group. The frequency of non-progressive disease, CA19-9 response, and favorable prognosis compared with the estimated survival, were 58%, 22%, and 60%, respectively, in the gemcitabine group, and 22%, 6%, 30%, respectively, in the non-gemcitabine group. The median survival time in the gemcitabine and non-gemcitabine group was 5.73 and 2.87 months, respectively., Conclusion: It is suggested that there was a definite improvement in pancreatic cancer treatment after gemcitabine was introduced.

Objective: The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer., Methods: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4)., Results: Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months., Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m(2)/week and an S-1 dose of 80 mg/m(2)/day in further studies with this schedule.

Background/aims: To examine the efficacy and safety of a combined modality therapy consisting of hepatic arterial infusion of 5-fluorouracil and external-beam radiotherapy in patients with advanced pancreatic carcinoma., Methodology: Hepatic arterial infusion chemotherapy consisted of 5-FU 1000mg/m2 administrated as a 5-hr continuous infusion once weekly. External-beam radiotherapy (total dose, 50Gy; 2Gy/day) was delivered to the pancreas tumor concurrently for 5-6 weeks. Seventeen patients with no distant metastases except to the liver were enrolled in this study., Results: Patients received a median of 13 cycles of chemotherapy. Sixteen of 17 patients received a total radiotherapy dose of 50Gy. In one patient, treatment was discontinued after 24Gy of radiotherapy and 2 cycles of chemotherapy because of progressive disease. Nausea and vomiting were the most common types of toxicity. Grade 3 or worse toxicity was observed in 2 patients. Four patients developed gastroduodenal ulcers. Of the 16 patients, 7 (41%) showed a partial response, and 9 (53%) showed no change. The median overall survival was 4.5 months and 1-yr overall survival of 11.8% was observed., Conclusions: The combined therapy is active and well tolerated, but results in a poorer prognosis, in spite of its high initial response rate.

Background: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU)., Methods: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method., Results: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months., Conclusions: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma., (Copyright 2003 American Cancer Society.)