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Objective: The aim of this study was to evaluate the efficacy and toxicity of S-1 in patients with metastatic pancreatic cancer. Methods: Patients were required to have a histological diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. S-1 was administered orally at 40 mg/m² twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. A pharmacokinetic study was done on day 1 in the initial 8 patients. Results: Nineteen patients were entered into this study. Four patients (21.1%) achieved a partial response with a 95% confidence interval of 6.1–45.6%. No change was noted in 10 patients (52.6%), and progressive disease in 5 patients (26.3%). The median survival time was 5.6 months with a one-year survival rate of 15.8%. The major adverse events were gastrointestinal toxicities such as nausea and anorexia, though most of them were tolerable and reversible. There were no large differences in the pharmacokinetic parameters of S-1 in patients with pancreatic cancer and those in patients with other cancers. Conclusion: S-1 is active and tolerated in patients with metastatic pancreatic cancer, which will be confirmed in the following large-scale phase II study.

BACKGROUND The aim of the current study was to evaluate the antitumor activity and toxicity of continuous infusion of 5‐fluorouracil, mitoxantrone, and cisplatin (FMP therapy) in chemotherapy‐naive patients with metastatic hepatocellular carcinoma (HCC). METHODS Fifty‐one patients with metastatic HCC who had not undergone previous systemic chemotherapy were enrolled. The therapy consisted of intravenous administration of 80 mg/m2 cisplatin and 6 mg/m2 mitoxantrone on Day 1 and continuous intravenous infusion of 450 mg/m2 5‐fluorouracil per day on Days 1–5. The treatment was repeated every 4 weeks for a maximum of 6 courses with dose adjustments based on the observed toxic effects if there was no evidence of tumor progression or unacceptable toxicity. RESULTS Of the 51 enrolled patients, 14 (27%) achieved a partial response (95% confidence interval, 16–42%) with a median duration of 7.6 months (range, 2.3–18.4 months). Twenty‐seven patients (53%) showed no change and 9 (18%) had progressive disease. The median survival time, 1‐year survival rate, and median progression‐free survival time for all patients were 11.6 months, 44.3%, and 4.0 months, respectively. The main Grade 3 and 4 toxicities were leukocytopenia (67%), neutropenia (71%), thrombocytopenia (27%), and elevated levels of aspartate aminotransferase (37%) and alanine aminotransferase (41%). These symptoms were generally brief and reversible, with the exception of one treatment‐related death due to acute hepatic failure. CONCLUSIONS FMP therapy had significant antitumor activity with acceptable toxicity in patients with metastatic HCC. Cancer 2005. © 2005 American Cancer Society.

Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m À2 , 30-min infusion). Maintenance gemcitabine (1000 mg m À2 weekly  3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.

Objectives: Chemoradiotherapy, which is one of the standard treatments for locally advanced pancreatic carcinoma, is considered a high-risk procedure in elderly patients. This study investigated the outcome and tolerability of this treatment in elderly patients. Methods: We reviewed our database from November 1993 to March 2003 and retrospectively examined the clinical data of patients with histologically confirmed exocrine pancreatic carcinomas that were nonresectable but confined to the pancreatic region, who were treated with protracted 5-fluorouracil infusion (200 mg/m²/day) and concurrent radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks). We evaluated the outcome of patients ≧70 years and those <70 years. Results: There were 19 patients ≧70 and 39 patients <70. On pretreatment evaluation, the elderly patients showed lower serum albumin levels, lower transaminase levels, better ECOG performance status, more frequent body weight loss and less frequent abdominal and/or back pain with the administration of morphine than the younger patients. There were no significant differences in the frequency of severe toxicity. Neither the response rate nor the incidence of treatment discontinuation differed significantly between the two groups. The median survival time was longer in the elderly patients than in the younger patients (11.3 vs. 9.5 months, p = 0.04). Conclusions: With careful patient selection, chemoradiotherapy can be one of the treatment options for locally advanced pancreatic carcinoma in elderly patients.