title: Phase I dose-escalation study of EZN-2208 (PEG-SN38), a novel conjugate of poly(ethylene) glycol and SN38, administered weekly in patients with advanced cancer.
abstract: OBJECTIVE
  This study evaluated the tolerability, pharmacokinetics, and preliminary antitumor activity of EZN-2208, a water-soluble poly(ethylene) glycol conjugate of SN38.
  
  
  METHODS
  Patients with advanced malignancies were enrolled in dose-escalating cohorts (3 + 3 design). EZN-2208 was administered as a 1-h intravenous infusion given weekly for 3 weeks per each 4-week cycle. Doses ranged from 1 to 12 mg/m(2).
  
  
  RESULTS
  Forty-one patients received EZN-2208. All patients had received prior cancer therapy (median = 2, range = 1-11). Twenty patients (49 %) had received prior irinotecan, and one patient had received prior topotecan. One patient in the 9-mg/m(2) cohort had dose-limiting toxicity (grade 3 febrile neutropenia), and one patient in the 12-mg/m(2) cohort had grade 3 neutropenia that resulted in the inability to deliver the third dose of EZN-2208. The most commonly reported drug-related adverse events were nausea (51 %), diarrhea (46 %), fatigue (41 %), alopecia (29 %), neutropenia (24 %), and vomiting (22 %). Administration of EZN-2208 results in prolonged exposure to SN38. Stable disease, sometimes prolonged, was observed as best response.
  
  
  CONCLUSIONS
  EZN-2208 has an acceptable safety profile in previously treated patients with advanced malignancies. The recommended phase II dose of EZN-2208 administered according to this schedule was 9 mg/m(2).
authors.affiliation: START (South Texas Accelerated Research Therapeutics), 4383 Medical Drive, Suite 4021, San Antonio, TX 78229-3307, USA. Amita.Patnaik@start.stoh.com
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
authors.forename: Kyriakos P
authors.initials: KP
authors.lastname: Papadopoulos
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Tolcher
authors.forename: Muralidhar
authors.initials: M
authors.lastname: Beeram
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Schaaf
authors.forename: Sanaa
authors.initials: S
authors.lastname: Tahiri
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: François M
authors.initials: FM
authors.lastname: Lokiec
authors.forename: Keyvan
authors.initials: K
authors.lastname: Rezaï
authors.forename: Aby
authors.initials: A
authors.lastname: Buchbinder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C528970:EZN-2208; D011355:Prodrugs; D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin
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