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

• Published in: British journal of cancer 2007-05, Vol.96 (9), p.1353-1357
• Main Authors: Shinchi, H, Maemura, K, Noma, H, Mataki, Y, Aikou, T, Takao, S
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - toxicity; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Oxonic Acid - toxicity; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - radiotherapy; Radiotherapy - methods; Survival Analysis; Tegafur - toxicity; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603735

In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy × 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m –2  day –1 on days 1–7 and 15–21 (level 1), 1–14 (level 2), and 1–21 (level 3a) and 80 mg m –2  day –1 on days 1–21 (level 3b) and 1–28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19–9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m –2  day –1 given on days 1–21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.