Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 6, pp 1499–1506

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

  • Amita Patnaik
  • Kyriakos P. Papadopoulos
  • Anthony W. Tolcher
  • Muralidhar Beeram
  • Saïk Urien
  • Larry J. Schaaf
  • Sanaa Tahiri
  • Tanios Bekaii-Saab
  • François M. Lokiec
  • Keyvan Rezaï
  • Aby Buchbinder
Original Article

DOI: 10.1007/s00280-013-2149-2

Cite this article as:
Patnaik, A., Papadopoulos, K.P., Tolcher, A.W. et al. Cancer Chemother Pharmacol (2013) 71: 1499. doi:10.1007/s00280-013-2149-2

Abstract

Purpose

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/m2.

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/m2 cohort had dose-limiting toxicity (grade 3 febrile neutropenia), and one patient in the 12-mg/m2 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/m2.

Keywords

Topoisomerase-1 inhibitorsSN38Polyethylene glycolPhase I clinical trials

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Amita Patnaik
    • 1
  • Kyriakos P. Papadopoulos
    • 1
  • Anthony W. Tolcher
    • 1
  • Muralidhar Beeram
    • 1
  • Saïk Urien
    • 2
  • Larry J. Schaaf
    • 3
  • Sanaa Tahiri
    • 3
  • Tanios Bekaii-Saab
    • 3
  • François M. Lokiec
    • 2
  • Keyvan Rezaï
    • 2
  • Aby Buchbinder
    • 4
  1. 1.START (South Texas Accelerated Research Therapeutics)San AntonioUSA
  2. 2.René Huguenin HospitalInstitut CurieSaint-CloudFrance
  3. 3.Arthur G. James Cancer HospitalThe Ohio State UniversityColumbusUSA
  4. 4.Enzon Pharmaceuticals Inc.PiscatawayUSA