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 Citations (Scopus)

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

Fingerprint

Ethylene Glycol
Polyethylene glycols
Neoplasms
irinotecan
Neutropenia
Topotecan
Pharmacokinetics
Febrile Neutropenia
EZN-2208
Alopecia
Drug-Related Side Effects and Adverse Reactions
Toxicity
Intravenous Infusions
Nausea
Vomiting
Fatigue
Diarrhea
Appointments and Schedules
Fatigue of materials
Water

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Cancer Chemotherapy and Pharmacology, Vol. 71, No. 6, 01.06.2013, p. 1499-1506.

Research output: Contribution to journalArticle

Patnaik, A, Papadopoulos, KP, Tolcher, AW, Beeram, M, Urien, S, Schaaf, LJ, Tahiri, S, Bekaii-Saab, T, Lokiec, FM, 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, vol. 71, no. 6, pp. 1499-1506. https://doi.org/10.1007/s00280-013-2149-2
Patnaik, Amita ; Papadopoulos, Kyriakos P. ; Tolcher, Anthony W. ; Beeram, Muralidhar ; Urien, Saïk ; Schaaf, Larry J. ; Tahiri, Sanaa ; Bekaii-Saab, Tanios ; Lokiec, François M. ; Rezaï, Keyvan ; Buchbinder, Aby. / 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. In: Cancer Chemotherapy and Pharmacology. 2013 ; Vol. 71, No. 6. pp. 1499-1506.
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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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T1 - 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

AU - Patnaik, Amita

AU - Papadopoulos, Kyriakos P.

AU - Tolcher, Anthony W.

AU - Beeram, Muralidhar

AU - Urien, Saïk

AU - Schaaf, Larry J.

AU - Tahiri, Sanaa

AU - Bekaii-Saab, Tanios

AU - Lokiec, François M.

AU - Rezaï, Keyvan

AU - Buchbinder, Aby

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

KW - Phase I clinical trials

KW - Polyethylene glycol

KW - SN38

KW - Topoisomerase-1 inhibitors

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