title: A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression.
abstract: BACKGROUND
  Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5'-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression.
  
  
  METHODS
  Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR).
  
  
  RESULTS
  Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate.
  
  
  CONCLUSIONS
  This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pant
authors.affiliation: Massachussetts General Hospital, Boston, MA, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: The Sydney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Laheru
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bahary
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: T
authors.initials: T
authors.lastname: Dragovich
authors.affiliation: Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hosein
authors.affiliation: Clovis Oncology, Cambridge, UK; Clovis Oncology, San Francisco, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rolfe
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Saif
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: LaValle
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lowery
authors.affiliation: Clovis Oncology, Cambridge, UK; Clovis Oncology, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Allen
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: oreillye@mskcc.org.
authors.forename: E M
authors.initials: EM
authors.lastname: O'Reilly
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C538828:CP 4126; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Biomarker; CO-1.01; Disease-control rate; Gemcitabine-refractory; Pancreas adenocarcinoma; hENT1