دورية أكاديمية
أعرض في EDS

Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies.

التفاصيل البيبلوغرافية
العنوان: Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies.
المؤلفون: Kunos CA; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA. charles.kunos@nih.gov.; Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, MSC 9739, Rockville, MD, 20892-9760, USA. charles.kunos@nih.gov., Chu E; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Beumer JH; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.; University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA., Sznol M; Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA., Ivy SP; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
المصدر: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2017 Jan; Vol. 79 (1), pp. 201-207. Date of Electronic Publication: 2016 Nov 22.
نوع المنشور: Clinical Trial, Phase I; Journal Article
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: Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Neoplasms/*drug therapy , Pyridines/*administration & dosage , Ribonucleotide Reductases/*antagonists & inhibitors , Thiosemicarbazones/*administration & dosage, Adult ; Aged ; Aged, 80 and over ; Cisplatin/administration & dosage ; Cisplatin/adverse effects ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/diagnosis ; Pyridines/adverse effects ; Pyridines/pharmacokinetics ; Thiosemicarbazones/adverse effects ; Thiosemicarbazones/pharmacokinetics
مستخلص: Purpose: Advanced-stage malignancies have increased deoxyribonucleotide demands in DNA replication and repair, making deoxyribonucleotide supply a potential exploitable target for therapy based on ribonucleotide reductase (RNR) inhibition.
Methods: A dose-finding phase I trial was conducted of intravenous (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in patients with advanced-stage solid tumor malignancies. Patients received dose-finding levels of i.v. triapine (48-96 mg/m 2 ) and i.v. cisplatin (20-75 mg/m 2 ) on 1 of 3 different schedules. The primary endpoint was to identify the maximum tolerated dose of a triapine-cisplatin combination. Secondary endpoints included the rate of triapine-cisplatin objective response and the pharmacokinetics and bioavailability of a single oral triapine dose. (Clinicaltrials.gov number, NCT00024323).
Results: The MTD was 96 mg/m 2 triapine daily days 1-4 and 75 mg/m 2 cisplatin split over day 2 and day 3. Frequent grade 3 or 4 adverse events included fatigue, dyspnea, leukopenia, thrombocytopenia, and electrolyte abnormalities. No objective responses were observed; 5 (50%) of 10 patients treated at the MTD had stable disease. Pharmacokinetics indicated an oral triapine bioavailability of 88%.
Conclusions: The triapine-cisplatin combination may be given safely in patients with advanced-stage solid tumor malignancies. On the basis of these results, a phase I trial adequately powered to evaluate oral triapine bioavailability in women with advanced-stage uterine cervix or vulvar cancers is underway.
Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interests.
References: J Natl Cancer Inst. 2000 Feb 2;92 (3):205-16. (PMID: 10655437)
Radiat Res. 2010 Nov;174(5):574-81. (PMID: 20954859)
Clin Cancer Res. 2006 May 1;12(9):2912-8. (PMID: 16675588)
Future Oncol. 2012 Feb;8(2):145-50. (PMID: 22335579)
Radiat Res. 2009 Dec;172(6):666-76. (PMID: 19929413)
Int J Gynecol Cancer. 2012 Nov;22(9):1463-9. (PMID: 23051959)
J Inorg Biochem. 2011 Nov;105(11):1422-31. (PMID: 21955844)
Gynecol Oncol. 2013 Jul;130(1):75-80. (PMID: 23603372)
Cancer Res. 2003 Mar 1;63(5):980-6. (PMID: 12615712)
Front Oncol. 2014 Jul 24;4:184. (PMID: 25105092)
Clin Cancer Res. 2010 Feb 15;16(4):1298-306. (PMID: 20145183)
Radiat Res. 2011 Oct;176(4):425-33. (PMID: 21756082)
Annu Rev Biochem. 1979;48:133-58. (PMID: 382982)
Int J Gynecol Cancer. 2013 May;23(4):615-21. (PMID: 23552804)
J Transl Med. 2012 Apr 27;10:79. (PMID: 22541066)
Nat Struct Mol Biol. 2011 Mar;18(3):316-22. (PMID: 21336276)
Philos Trans R Soc Lond B Biol Sci. 2006 Aug 29;361(1472):1351-64. (PMID: 16873123)
J Biol Chem. 2006 Mar 24;281(12 ):7834-41. (PMID: 16436374)
معلومات مُعتمدة: P30 CA047904 United States CA NCI NIH HHS; UM1 CA186690 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Advanced malignancies; Cisplatin; Dose-limiting toxicity; Maximum tolerated dose; Oral bioavailability; Phase I clinical trial; Triapine
سلسلة جزيئية: ClinicalTrials.gov NCT00024323
المشرفين على المادة: 0 (Pyridines)
0 (Thiosemicarbazones)
143621-35-6 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone)
EC 1.17.4.- (Ribonucleotide Reductases)
Q20Q21Q62J (Cisplatin)
تواريخ الأحداث: Date Created: 20161124 Date Completed: 20170602 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5226891
DOI: 10.1007/s00280-016-3200-x
PMID: 27878356
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0843
DOI:10.1007/s00280-016-3200-x