title: Multicenter trial of EC145 in advanced, folate-receptor positive adenocarcinoma of the lung.
abstract: BACKGROUND
  EC145 is a novel folate-receptor targeted agent consisting of a folate molecule linked to a vinca alkaloid. EC20 is a technetium-labeled folate that assesses the presence of folate receptors (FR) in vivo. The objective of this study was to determine the activity of EC145 in patients with chemotherapy refractory lung adenocarcinoma, whose tumors expressed the FR as determined by EC20 imaging.
  
  
  METHODS
  Patients with advanced adenocarcinoma of the lung, Eastern Cooperative Oncology Group performance status 0 to 2, normal organ function, those who had progressed after at least two prior cytotoxic regimens, and with EC 20 uptake in at least one index lesion were eligible. The primary objective of the study was the ability to receive four or more cycles of therapy.
  
  
  RESULTS
  Sixty patients were screened and 43 patients were enrolled. Eleven patients (26%) received more than four cycles (95% confidence interval [CI] 14%, 41%), and one patient had partial response (response rate (RR) = 2.3%, 95% CI 0%, 12%). Patients in whom all target tumor lesions expressed FR by EC 20 scans had a trend toward superior results in terms of clinical benefit response (50% versus 14.3 %; p = 0.10) and survival (47.2 weeks versus 14.9 weeks [HR = 0.539, p = 0.101]) compared with those in whom at least one but not all target lesions were positive for FR (FR+).
  
  
  CONCLUSIONS
  EC145 demonstrated clinical activity with a good toxicity profile in this population. Uniform uptake of EC20 may predict activity of EC145 and be useful for prospective selection of patients in future trials.
authors.affiliation: University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA. medelman@umm.edu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Wael A
authors.initials: WA
authors.lastname: Harb
authors.forename: Sridhar E
authors.initials: SE
authors.lastname: Pal
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kraut
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Conley
authors.forename: John S
authors.initials: JS
authors.lastname: Rogers
authors.forename: Richard A
authors.initials: RA
authors.lastname: Messmann
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm; D005260:Female; D058975:Folate Receptor 1 / Q000378:metabolism*; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009842:Oligopeptides; D011379:Prognosis; D015996:Survival Rate; D014748:Vinca Alkaloids / Q000627:therapeutic use*
chemical_list: C520389:EC145; C473829:EC20 folate peptide; D058975:Folate Receptor 1; D009842:Oligopeptides; D014748:Vinca Alkaloids; D005492:Folic Acid