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

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1499-1506
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume71
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

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Keywords

  • Phase I clinical trials
  • Polyethylene glycol
  • SN38
  • Topoisomerase-1 inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Patnaik, A., Papadopoulos, K. P., Tolcher, A. W., Beeram, M., Urien, S., Schaaf, L. J., Tahiri, S., Bekaii-Saab, T., Lokiec, F. M., Rezaï, K., & Buchbinder, A. (2013). 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. Cancer Chemotherapy and Pharmacology, 71(6), 1499-1506. https://doi.org/10.1007/s00280-013-2149-2