An Early Phase II Study of S-1 in Patients with Metastatic Pancreatic Cancer

Abstract

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.

A Case of Pancreatic Cancer After Heart Transplantation

“…11) We selected S-1, another active drug in Asian countries including Japan, for pancreatic cancer. S-1 showed noninferiority to gemcitabine in Japanese large-scale trials, 12,13) and we also previously reported that S-1 improved the survival time of patients with unresectable pancreatic cancer. 14,15) Mycophenolate mofetile was discontinued because both mycophenolate mofetile and S-1 combination share the characteristics of DNA synthesis inhibition and simultaneous administration of the two drugs may increase the risk of myelosuppression.…”

Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer

“…5-fluorouracil has been used for chemoradiation because it can enhance the effects of radiation (Whittington et al, 1995;Ishii et al, 1997). The novel oral anticancer agent S-1 was developed to improve the tumor-selective toxicity of 5-FU and has shown a good efficacy for a variety of solid tumours, including pancreatic cancer (Koizumi et al, 2000;Ohtsu et al, 2000;Kawahara et al, 2001;Ueno et al, 2005). Thus, S-1 may also act as a radiosensitizer because it has cytotoxic mechanisms similar to those of 5-FU (Hirata et al, 1999;Hoff et al, 2003;Schoffski, 2004).…”

“…S-1 has already undergone phase I and phase II testing in several solid tumours in Japan and Western countries (Koizumi et al, 2000;Ohtsu et al, 2000;van Groeningen et al, 2000;Kawahara et al, 2001;Hoff et al, 2003;Ueno et al, 2005;Nakamura et al, 2006). The main adverse reaction was myelosuppression in a Japanese phase-I study, and diarrhoea in a European and a North-American phase-I study (van Groeningen et al, 2000;Hoff et al, 2003).…”

“…Recent clinical trials of S-1 have shown promising results in various solid tumours (Koizumi et al, 2000;Ohtsu et al, 2000;Kawahara et al, 2001). In an early phase-II clinical study for metastatic pancreatic cancer in Japan, the objective response rate of S-1 as a single agent was 21.1% (4/19) (Ueno et al, 2005).…”

S-1 Salvage Chemotherapy for Esophageal Squamous Cell Carcinoma Refractory to the Standard Chemotherapy

“…During the past decade, several phase II studies demonstrated the efficacy of S-1 in major solid cancers. Response rates of S-1 were 45.0% in gastric cancer [6,7], 32.6% in colorectal cancer [8,9], 18.2% in lung cancer [10,11], 41.7% in breast cancer [12], and 32.2% in pancreatic cancer [13,14]. In addition, the response rate of S-1 was 34.1% in head and neck cancer [15,16].…”