Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 6, pp 1499–1506 | Cite as

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

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 inhibitors SN38 Polyethylene glycol Phase I clinical trials 

Notes

Acknowledgments

The authors thank Arlene Reiss and Hana Fainman (consultant medical writers for Enzon) for their assistance in the manuscript preparation.

Conflict of interest

Employment and Stock Ownership: Aby Buchbinder, Enzon; Advisory Role: Anthony Tolcher (Uncompensated); Honoraria: François Lokiec, Keyvan Rezaï, Saïk Urien; Research Funding: Muralidhar Beeram, Kyriakos Papadopoulos, Amita Patnaik, Anthony Tolcher.

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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

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