title: Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients.
abstract: OBJECTIVE
  There is no standard regimen for gemcitabine (Gem)-refractory pancreatic cancer (PC) patients. In a previous phase II trial, S-1 was found to exhibit marginal efficacy. Gem administration by fixed dose rate infusion of 10 mg/m(2)/min (FDR-Gem) should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. We conducted the phase I/II of FDR-Gem and S-1 (FGS) in patients with Gem-refractory PC.
  
  
  METHODS
  The patients received FDR-Gem on day 1 and S-1 orally twice daily on days 1-7. Cycles were repeated every 14 days. Patients were scheduled to receive Gem (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels in the phase I: 800/80 (level 1), 1,000/80 (level 2), 1,200/80 (level 3) and 1,200/100 (level 4). Forty patients were enrolled in the phase II study at recommended dose.
  
  
  RESULTS
  The recommended dose was the level 3. In the phase II, a partial response has been confirmed in seven patients (18%). The median overall survival time and median progression-free survival time are 7.0 and 2.8 months, respectively. The common adverse reactions were anorexia, leukocytopenia and neutropenia.
  
  
  CONCLUSIONS
  This combination regimen of FGS is active and well tolerated in patients with Gem-refractory PC.
authors: Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. cmorizan@ncc.go.jp
authors: Chigusa
authors: C
authors: Morizane
authors: Takuji
authors: T
authors: Okusaka
authors: Hideki
authors: H
authors: Ueno
authors: Shunsuke
authors: S
authors: Kondo
authors: Masafumi
authors: M
authors: Ikeda
authors: Junji
authors: J
authors: Furuse
authors: Ohkawa
authors: O
authors: Shinichi
authors: Kohei
authors: K
authors: Nakachi
authors: Shuichi
authors: S
authors: Mitsunaga
authors: Yasushi
authors: Y
authors: Kojima
authors: Eiichiro
authors: E
authors: Suzuki
authors: Makoto
authors: M
authors: Ueno
authors: Tomohiro
authors: T
authors: Yamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine