title: Phase I study of folate conjugate EC145 (Vintafolide) in patients with refractory solid tumors.
abstract: OBJECTIVE
  EC145 (vintafolide), a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a ligand for the folate receptor (FR), with activity against FR-positive tumor xenografts in vivo. This phase I study determined the maximum-tolerated dose (MTD) of EC145 administered as a bolus intravenous injection or 1-hour infusion in patients with refractory solid tumors.
  
  
  METHODS
  EC145 was administered as a bolus injection or 1-hour infusion on days 1, 3, and 5 and days 15, 17, and 19 of each 28-day cycle with dose escalation in cohorts of three to six patients until the MTD was identified. Plasma pharmacokinetics were determined on days 1 and 3 of the first cycle.
  
  
  RESULTS
  The MTD of EC145 was 2.5 mg when administered as either a bolus injection or 1-hour infusion. Constipation was the dose-limiting toxicity with both routes. Constipation, nausea, fatigue, and vomiting were the most commonly reported adverse events. One partial response to therapy was observed in a patient with metastatic ovarian cancer.
  
  
  CONCLUSIONS
  EC145 administered by bolus injection or as a 1-hour infusion at a dose of 2.5 mg on days 1, 3, and 5 and days 15, 17, and 19 of a 28-day cycle has an acceptable safety profile in patients with advanced cancer. On the basis of these findings, phase II studies of EC145 have been initiated in patients with advanced epithelial ovarian cancer and non-small-cell lung cancer.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, 22 S. Greene St, Baltimore, MD 21201, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Lorusso
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Susan L
authors.initials: SL
authors.lastname: Bever
authors.forename: Karen M
authors.initials: KM
authors.lastname: Forman
authors.forename: Maryjo
authors.initials: M
authors.lastname: Pilat
authors.forename: Mary F
authors.initials: MF
authors.lastname: Quinn
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Malburg
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Klein
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Leamon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Messmann
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sausville
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D003248:Constipation / Q000139:chemically induced; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D012720:Severity of Illness Index; D014748:Vinca Alkaloids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; C520389:EC145; D014748:Vinca Alkaloids; D005492:Folic Acid