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01.06.2013 | Original Article

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

verfasst von: 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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2013

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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.

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Titel: 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
verfasst von: 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
Publikationsdatum: 01.06.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2149-2

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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