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Thompson, Patrick A.; Drissi, Rachid; Muscal, Jodi A.; Panditharatna, Eshini; Fouladi, Maryam; Ingle, Ashish M.; Ahern, Charlotte H.; Reid, Joel M.; Lin, Tong; Weigel, Brenda J.; Blaney, Susan M.

A Phase I Trial of Imetelstat in Children with Refractory or Recurrent Solid Tumors: A Children's Oncology Group Phase I Consortium Study (ADVL1112)

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  • Medientyp: E-Artikel
  • Titel: A Phase I Trial of Imetelstat in Children with Refractory or Recurrent Solid Tumors: A Children's Oncology Group Phase I Consortium Study (ADVL1112)
  • Beteiligte: Thompson, Patrick A.; Drissi, Rachid; Muscal, Jodi A.; Panditharatna, Eshini; Fouladi, Maryam; Ingle, Ashish M.; Ahern, Charlotte H.; Reid, Joel M.; Lin, Tong; Weigel, Brenda J.; Blaney, Susan M.
  • Erschienen: American Association for Cancer Research (AACR), 2013
  • Erschienen in: Clinical Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-13-1117
  • ISSN: 1078-0432; 1557-3265
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Purpose: Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate oligonucleotide that acts as a potent specific inhibitor of telomerase. It binds with high affinity to the template region of the RNA component of human telomerase (hTERC) and is a competitive inhibitor of telomerase enzymatic activity. The purpose of this study was to determine the recommended phase II dose of imetelstat in children with recurrent or refractory solid tumors.</jats:p> <jats:p>Experimental Design: Imetelstat was administered intravenously more than two hours on days 1 and 8, every 21 days. Dose levels of 225, 285, and 360 mg/m2 were evaluated, using the rolling-six design. Imetelstat pharmacokinetic and correlative biology studies were also performed during the first cycle.</jats:p> <jats:p>Results: Twenty subjects were enrolled (median age, 14 years; range, 3–21). Seventeen were evaluable for toxicity. The most common toxicities were neutropenia, thrombocytopenia, and lymphopenia, with dose-limiting myelosuppression in 2 of 6 patients at 360 mg/m2. Pharmacokinetics is dose dependent with a lower clearance at the highest dose level. Telomerase inhibition was observed in peripheral blood mononuclear cells at 285 and 360 mg/m2. Two confirmed partial responses, osteosarcoma (n = 1) and Ewing sarcoma (n = 1), were observed.</jats:p> <jats:p>Conclusions: The recommended phase II dose of imetelstat given on days 1 and 8 of a 21-day cycle is 285 mg/m2. Clin Cancer Res; 19(23); 6578–84. ©2013 AACR.</jats:p>
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