title: Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study).
abstract: OBJECTIVE
  To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer.
  
  
  METHODS
  In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival.
  
  
  RESULTS
  We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group).
  
  
  CONCLUSIONS
  The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. masato.ozaka@jfcr.or.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Ozaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Omuro
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Mouri
authors.forename: Keiji
authors.initials: K
authors.lastname: Hanada
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Iruru
authors.initials: I
authors.lastname: Maetani
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okabe
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Susumu
authors.initials: S
authors.lastname: Hijioka
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohoka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirose
authors.forename: Masafumi
authors.initials: M
authors.lastname: Suyama
authors.forename: Naoto
authors.initials: N
authors.lastname: Egawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sofuni
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikari
authors.forename: Toshifusa
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine