title: A multicenter phase II trial of gemcitabine and candesartan combination therapy in patients with advanced pancreatic cancer: GECA2.
abstract: BACKGROUND
  Our retrospective study and phase I trial of gemcitabine and candesartan combination therapy suggested the inhibition of renin-angiotensin system potentially has a role in the treatment of advanced pancreatic cancer. The aim of this multicenter phase II trial was to assess the efficacy and toxicity of gemcitabine and candesartan combination therapy for advanced pancreatic cancer.
  
  
  METHODS
  Chemotherapy-naive patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m(2) over 30 min on days 1, 8, and 15 and oral candesartan at a dose of 16 mg in normotensive patients, and 8 mg initially in hypertensive patients, with dose escalation to 16 mg allowed, from days 1 to 28, repeated every 4 weeks.
  
  
  RESULTS
  A total of 35 patients with advanced pancreatic cancer were enrolled. Overall response rate and disease control rate were 11.4 % and 62.9 %. The median PFS and OS were 4.3 and 9.1 months with 1-year survival rate of 34.2 %. The median PFS was significantly longer in patients receiving 16 mg compared with 8 mg of candesartan (4.6 vs. 3.5 months, p=0.031). Major severe toxicities were neutropenia (23 %), leukopenia (17 %) and thrombocytopenia (11 %). Grade 2 hypotension was observed in 3 patients (9 %) and candesartan was discontinued in 2 patients due to hypotension. Conclusions In this multicenter phase 2 trial, gemcitabine and candesartan combination therapy was tolerable but failed to demonstrate activity against advanced pancreatic cancer. (UMIN CTR: UMIN000005580).
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, Japan, 113-8655.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Nakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isayama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ijichi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naminatsu
authors.initials: N
authors.lastname: Takahara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Saburo
authors.initials: S
authors.lastname: Matsubara
authors.forename: Rie
authors.initials: R
authors.lastname: Uchino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagioka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Arizumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamada
authors.forename: Koji
authors.initials: K
authors.lastname: Miyabayashi
authors.forename: Suguru
authors.initials: S
authors.lastname: Mizuno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kogure
authors.forename: Natsuyo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirano
authors.forename: Naoki
authors.initials: N
authors.lastname: Sasahira
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.forename: Minoru
authors.initials: M
authors.lastname: Tada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D001713:Biphenyl Compounds; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000964:Antimetabolites, Antineoplastic; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003841:Deoxycytidine; C081643:candesartan; D000093542:Gemcitabine