title: Phase I trial of gemcitabine and candesartan combination therapy in normotensive patients with advanced pancreatic cancer: GECA1.
abstract: Our retrospective study showed inhibition of the renin-angiotensin system was associated with better outcomes in patients with advanced pancreatic cancer receiving gemcitabine. The primary objective of this phase I study was to determine the recommended dose of candesartan in combination with gemcitabine in normotensive patients with advanced pancreatic cancer. Candesartan was given orally at an escalating dose (4, 8, 16, and 32 mg) q.d. daily, and gemcitabine was given 1000 mg/m(2) 30 min i.v. on days 1, 8, and 15, repeated every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicities, grade 2 hypotension, abnormal creatinine or potassium, and grade 3 or 4 other non-hematological toxicities. A standard "3+3" phase I dose-escalation design was used. A total of 14 patients (candesartan 4 mg, three patients; 8 mg, three patients; 16 mg, six patients; 32 mg, two patients) were enrolled. One of six patients at 16 mg showed DLT of grade 4 neutropenia and two of two patients at 32 mg showed DLT of grade 2 hypotension. Response rate and disease control rate were 0% and 79%, respectively. Progression-free survival and overall survival were 7.6 and 22.9 months, respectively. Candesartan 16 mg is the recommended dose in combination with gemcitabine in the treatment of advanced pancreatic cancer. (UMIN CTR: UMIN000002152).
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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: Hirofumi
authors.initials: H
authors.lastname: Kogure
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagioka
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: Dai
authors.initials: D
authors.lastname: Mouri
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Kawakubo
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: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000959:Antihypertensive Agents; D000964:Antimetabolites, Antineoplastic; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003841:Deoxycytidine; C081643:candesartan; D000093542:Gemcitabine