The DOI matches its Crossref record; its reference list is not available.
Phase 1 evaluation of EZN-2208, a polyethylene glycol conjugate of SN38, in children adolescents and young adults with relapsed or refractory solid tumors: Phase 1 Trial of EZN2208
Abstract
Background EZN-2208 is a water-soluble PEGylated conjugate of the topoisomerase inhibitor SN38, the active metabolite of irinotecan. Compared to irinotecan, EZN-2208 has a prolonged half-life permitting extended exposure to SN38. EZN-2208 has demonstrated clinical tolerability and antitumor activity in adults with advanced solid tumors. This Phase 1 study evaluated the safety, pharmacokinetics, and preliminary antitumor activity of EZN-2208 in children with relapsed or refractory solid tumors. Procedure EZN-2208 was administered as a 1-hour intravenous infusion once every 21 days at five dose levels (12-30 mg/m(2) ). Filgrastim or pegfilgrastim was administered 24-48 hours after treatment with EZN-2208. The rolling-six design was used for dose determination. Results Thirty eligible patients (15 females; median [range] age 11.5 years [2-21 years]) were treated with EZN-2208. Dose-limiting diarrhea occurred in one patient receiving 16 mg/m(2) and dose-limiting dehydration was seen in one patient receiving 24 mg/m(2) . At dose levels above 16 mg/m(2) , Grade ≥3 myelosuppression was demonstrated in the majority of patients. Additional adverse events included nausea, vomiting, and fatigue. The maximum tolerated dose was identified as 24 mg/m(2) due to dose-limiting thrombocytopenia in two patients receiving 30 mg/m(2) . Two of nine patients with neuroblastoma who were evaluable for response had partial responses. Five patients (four with neuroblastoma) remained on study for ≥8 cyc…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PEG-SN38 (or EZN-2208) has been shown to downregulate both HIF-1α and HIF-2α in a neuroblastoma model.
“PEG-SN38 (or EZN-2208) has been shown to downregulate both HIF-1α and HIF-2α in a neuroblastoma model (Pastorino et al., 2010), and a phase I study of PEG-SN38 in patients with neuroblastoma and other solid tumors showed low toxicity and supported further study of this drug in neuroblastoma (Norris et al., 2014).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Norris et al., 2014
Citations
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 35 · Cited by 38
Research works printed but not linked: 34
- Pappo, 2007, Two consecutive Phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: The Children's Oncology Group, J Clin Oncol, 25, 362, 10.1200/JCO.2006.07.1720 · DOI
- Bisogno, 2006, Phase II study of a protracted irinotecan schedule in children with refractory or recurrent soft tissue sarcoma, Cancer, 106, 703, 10.1002/cncr.21629 · DOI
- Bagatell, 2011, Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: A Children's Oncology Group study, J Clin Oncol, 29, 208, 10.1200/JCO.2010.31.7107 · DOI
- Casey, 2009, Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience, Pediatr Blood Cancer, 53, 1029, 10.1002/pbc.22206 · DOI
- Bomgaars, 2006, A Phase I study of irinotecan administered on a weekly schedule in pediatric patients, Pediatr Blood Cancer, 46, 50, 10.1002/pbc.20355 · DOI
- Trobaugh-Lotrario, 2012, Relapsed hepatoblastoma, Pediatr Blood Cancer, 59, 813, 10.1002/pbc.24218 · DOI
- Wolff, 2012, Treatment of recurrent diffuse intrinsic pontine glioma: The MD Anderson Cancer Center experience, J Neurooncol, 106, 391, 10.1007/s11060-011-0677-3 · DOI
- Vassal, 2007, Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: A joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group, J Clin Oncol, 25, 356, 10.1200/JCO.2006.06.1960 · DOI
- Chabot, 1997, Clinical pharmacokinetics of irinotecan, Clin Pharmacokinet, 33, 245, 10.2165/00003088-199733040-00001 · DOI
- Sapra, 2008, Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model, Clin Cancer Res, 14, 1888, 10.1158/1078-0432.CCR-07-4456 · DOI · Paper page
- Pastorino, 2010, Tumor regression and curability of preclinical neuroblastoma models by PEGylated SN38 (EZN-2208), a novel topoisomerase I inhibitor, Clin Cancer Res, 16, 4809, 10.1158/1078-0432.CCR-10-1354 · DOI · Paper page
- Kurzrock, 2012, Safety, pharmacokinetics, and activity of EZN-2208 a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies, Cancer, 118, 6144, 10.1002/cncr.27647 · DOI · Paper page
- Skolnik, 2008, Shortening the timeline of pediatric Phase I trials: The rolling six design, J Clin Oncol, 26, 190, 10.1200/JCO.2007.12.7712 · DOI
- Therasse, 2000, New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States National Cancer Institute of Canada, J Natl Cancer Inst, 92, 205, 10.1093/jnci/92.3.205 · DOI · Paper page
- Macdonald, 1990, Response criteria for Phase II studies of supratentorial malignant glioma, J Clin Oncol, 8, 1277, 10.1200/JCO.1990.8.7.1277 · DOI · Paper page
- Henson, 2008, Brain tumor imaging in clinical trials, Am J Neuroradiol, 29, 419, 10.3174/ajnr.A0963 · DOI
- Patnaik, 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 Chemother Pharmacol, 71, 1499, 10.1007/s00280-013-2149-2 · DOI
- Lee, 2005, Pediatric Phase I trials in oncology: An analysis of study conduct efficiency, J Clin Oncol, 23, 8431, 10.1200/JCO.2005.02.1568 · DOI
- Carlson, 1996, Pediatric Phase I drug tolerance: A review and comparison of recent adult and pediatric Phase I trials, J Pediatr Hematol Oncol, 18, 250, 10.1097/00043426-199608000-00003 · DOI
- Mugishima, 2002, Phase I study of irinotecan in pediatric patients with malignant solid tumors, J Pediatr Hematol Oncol, 24, 94, 10.1097/00043426-200202000-00007 · DOI
- Catimel, 1995, Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors, Ann Oncol, 6, 133, 10.1093/oxfordjournals.annonc.a059108 · DOI
- Furman, 1999, Direct translation of a protracted irinotecan schedule from a xenograft model to a Phase I trial in children, J Clin Oncol, 17, 1815, 10.1200/JCO.1999.17.6.1815 · DOI
- Blaney, 2001, A Phase I study of irinotecan in pediatric patients: A pediatric oncology group study, Clin Cancer Res, 7, 32
- Vassal, 2003, A Phase I study of irinotecan as a 3-week schedule in children with refractory or recurrent solid tumors, J Clin Oncol, 21, 3844, 10.1200/JCO.2003.08.175 · DOI
- Bomgaars, 2007, Phase II trial of irinotecan in children with refractory solid tumors: A Children's Oncology Group Study, J Clin Oncol, 25, 4622, 10.1200/JCO.2007.11.6103 · DOI
- Houghton, 2000, Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models, Clin Cancer Res, 6, 4110
- Wagner, 2004, Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors, Clin Cancer Res, 10, 840, 10.1158/1078-0432.CCR-03-0175 · DOI
- Kushner, 2006, Irinotecan plus temozolomide for relapsed or refractory neuroblastoma, J Clin Oncol, 24, 5271, 10.1200/JCO.2006.06.7272 · DOI
- Rubie, 2006, Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: A joint Societe Francaise des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study, J Clin Oncol, 24, 5259, 10.1200/JCO.2006.06.1572 · DOI
- Jeong, 2014, Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors, Investigational new drugs, 32, 340, 10.1007/s10637-013-0048-3 · DOI
- Garrett, 2013, Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer, Cancer, 119, 4223, 10.1002/cncr.28358 · DOI · Paper page
- Walsh, 2012, Pharmacokinetics and antitumor efficacy of XMT-1001, a novel, polymeric topoisoerase inhibitor, in mice bearing HT-29 human colon carcinoma xenografts, Clinical Cancer Research: an official journal of the American Association for Cancer Research, 18, 2591, 10.1158/1078-0432.CCR-11-1554 · DOI
- Vergote, 2013, Randomized multicenter phase II trial comparing two schedules of etirinotecan (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer, Journal of clinical oncology: Official journal of the American Society of Clinical Oncology, 31, 4060, 10.1200/JCO.2012.45.1278 · DOI
- Awada, 2013, Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomized phase 2 study, The Lancet Oncology, 14, 1216, 10.1016/S1470-2045(13)70429-7 · DOI
Metadata
- Authors
- Norris, R. E., Shusterman, S., Gore, L., Muscal, J. A., Macy, M. E., Fox, E., Berkowitz, N., Buchbinder, A., & Bagatell, R.
- Affiliations
- University Hospitals Cleveland Medical Center (US)
- Boston Children's Hospital (US)
- Children's Hospital Colorado (US)
- Baylor College of Medicine (US)
- Children's Hospital of Philadelphia (US)
- Enzon Pharmaceuticals (United States) (US)
- Corresponding author
- Norris, Robin E.
- ORCID
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2014-06-24
- Volume
- 61
- Issue
- 10
- Pages
- 1792-1797
- ISSN
- 1545-5009 (ISSN-L)
- OpenAlex
- W1536103762
- Cited by
- 38
- References
- 35
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 2
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pediatric Blood & Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Enzon Pharmaceuticals, Inc.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Keywords
- SN-38, irinotecan metabolite, relapsed or refractory solid tumors, pediatric oncology, neuroblastoma, maximum tolerated dose, dose-limiting toxicity, thrombocytopenia, myelosuppression, pharmacokinetics, anticancer activity, filgrastim
- MeSH terms
- Adolescent, Antineoplastic Agents, Camptothecin, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Humans, Male, Neoplasm Recurrence, Local, Neoplasms, Polyethylene Glycols, Treatment Outcome, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
