دورية أكاديمية
أعرض في EDS

A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors.

التفاصيل البيبلوغرافية
العنوان: A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors.
المؤلفون: Tolcher AW; South Texas Accelerated Research Therapeutics (START), LLC, San Antonio, TX, USA., Rodrigueza WV, Rasco DW, Patnaik A, Papadopoulos KP, Amaya A, Moore TD, Gaylor SK, Bisgaier CL, Sooch MP, Woolliscroft MJ, Messmann RA
المصدر: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2014 Feb; Vol. 73 (2), pp. 363-71. Date of Electronic Publication: 2013 Dec 03.
نوع المنشور: Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0843 (Electronic) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer International.
مواضيع طبية MeSH: Neoplasms/*drug therapy , Oligodeoxyribonucleotides/*administration & dosage , Oligonucleotides/*administration & dosage , Proto-Oncogene Proteins c-bcl-2/*genetics, Adult ; Aged ; Aged, 80 and over ; DNA/antagonists & inhibitors ; Female ; Humans ; Liposomes/administration & dosage ; Male ; Maximum Tolerated Dose ; Middle Aged ; Molecular Targeted Therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Oligonucleotides/adverse effects ; Oligonucleotides/pharmacokinetics ; Treatment Outcome
مستخلص: Purpose: Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were assessed in this phase 1 study of PNT2258, a BCL-2-targeted liposomal formulation of a 24-base DNA oligonucleotide called PNT100.
Methods: Patients with malignant solid tumors were assigned sequentially to one of ten dose-escalation cohorts of PNT2258 at 1, 2, 4, 8, 16, 32, 64, 85, 113, and 150 mg/m(2) administered intravenously on days 1 through 5 of each 21-day cycle. Pharmacokinetics were determined on days 1 and 5 of the first cycle. Lymphocyte and platelets concentrations were measured for evidence of BCL2-targeted effect. CT scans were used to identify radiologic evidence of anti-tumor effect.
Results: Twenty-two subjects received PNT2258, and the maximum tolerated dose for PNT2258 was not reached. Doses at or above 32 mg/m(2) resulted in exposure to PNT2258 above the exposure level required for anti-tumor activity in preclinical xenograft testing of 22,377 ng h/ml (PK analysis 2012). Fatigue was the most commonly reported adverse event. Dose-limiting toxicity, manifesting as a transient increase in aspartate aminotransferase, occurred at 150 mg/m(2), the highest dose tested. Four subjects, two each with diagnosis of non-small-cell lung cancer and sarcoma, treated at doses of 64 mg/m(2) or higher, remained on study for 5-8 cycles.
Conclusions: PNT2258 was safe and well tolerated at the doses tested up to 150 mg/m(2). Exposure to PNT2258 resulted in clinically manageable decreases in lymphocyte and platelet concentrations.
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المشرفين على المادة: 0 (Liposomes)
0 (Oligodeoxyribonucleotides)
0 (Oligonucleotides)
0 (PNT100)
0 (Proto-Oncogene Proteins c-bcl-2)
9007-49-2 (DNA)
تواريخ الأحداث: Date Created: 20131204 Date Completed: 20140623 Latest Revision: 20240807
رمز التحديث: 20240807
مُعرف محوري في PubMed: PMC3909249
DOI: 10.1007/s00280-013-2361-0
PMID: 24297683
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0843
DOI:10.1007/s00280-013-2361-0