title: Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer.
abstract: OBJECTIVE
  Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed.
  
  
  METHODS
  Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes.
  
  
  RESULTS
  In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91).
  
  
  CONCLUSIONS
  Apricoxib did not improve PFS, despite biomarker-driven patient selection.
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA. medelman@umm.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tan
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Fidler
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sanborn
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Greg
authors.initials: G
authors.lastname: Otterson
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Evans
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Schneider
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Roger
authors.initials: R
authors.lastname: Keresztes
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: John S
authors.initials: JS
authors.lastname: Rogers
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Jorge Antunez
authors.initials: JA
authors.lastname: de Mayolo
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Feliciano
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Medeiros
authors.affiliation: Martin J. Edelman, Josephine Feliciano, Yang Yang, and Michelle Medeiros, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Ming T. Tan, Georgetown University, Washington, DC; Mary J. Fidler, Rush University Medical Center, Chicago, IL; Rachel E. Sanborn, Providence Portland Medical Center, Portland, OR; Greg Otterson, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Lecia V. Sequist, Massachusetts General Hospital Cancer Center, Boston, MA; Tracey L. Evans, University of Pennsylvania, Philadelphia, PA; Bryan J. Schneider, Weill Cornell Medical College, New York City; Roger Keresztes, State University of New York Stony Brook, Stony Brook, NY; John S. Rogers, West Virginia University School of Medicine, Morgantown, WV; Jorge Antunez de Mayolo, Mercy Research Institute, Miami, FL; and Sara L. Zaknoen, Tragara, San Diego, CA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Zaknoen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D000068437:Pemetrexed; D011453:Prostaglandins / Q000652:urine*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005971:Glutamates; D011453:Prostaglandins; D011758:Pyrroles; D013449:Sulfonamides; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; C514354:apricoxib; D006147:Guanine; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human