Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: A pediatric brain tumor consortium study

Clinical Cancer Research

Volumn 14, Issue 4, 2008, Pages 1124-1130

  Gururangan, Sridharan ^a   Turner, Christopher D ^b   Stewart, Clinton F ^c   O'Shaughnessy, Melinda ^c   Kocak, Mehmet ^d   Poussaint, Tina Young ^b   Phillips, Peter C ^e   Goldman, Stewart ^f   Packer, Roger ^g   Pollack, Ian F ^h   Blaney, Susan M ⁱ   Karsten, Verena ^j   Gerson, Stanton L ^k   Boyett, James M ^d   Friedman, Henry S ^a   Kun, Larry E ^d  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^d Operations and Biostatistics Center   (United States)

^e CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^f CHILDREN'S MEMORIAL HOSPITAL   (United States)

^g CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

^h CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

ⁱ BAYLOR COLLEGE OF MEDICINE   (United States)

^j Vion Pharmaceuticals Incorporated   (United States)

^k CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

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Author keywords

[No Author keywords available]

Indexed keywords

6 O ALKYLGUANINE DNA ALKYLTRANSFERASE; CARBOPLATIN; CISPLATIN; CLORETAZINE; CYCLOPHOSPHAMIDE; ETOPOSIDE; VINCRISTINE;

ADOLESCENT; ADULT; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BONE MARROW SUPPRESSION; BRAIN TUMOR; CELL LEVEL; CHILD; CHILDHOOD CANCER; CLINICAL ARTICLE; CLINICAL TRIAL; CORRELATION ANALYSIS; DELAYED PLATELET RECOVERY; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG RESPONSE; DRUG WITHDRAWAL; FATIGUE; FEMALE; FOLLOW UP; HUMAN; IMAGE ANALYSIS; INFANT; KIDNEY FAILURE; LUNG INFILTRATE; MALE; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PLEURA EFFUSION; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; SEPSIS; THROMBOCYTOPENIA; TUMOR RECURRENCE; VOMITING;

ADOLESCENT; ADULT; ANTINEOPLASTIC AGENTS; AREA UNDER CURVE; BRAIN NEOPLASMS; CHILD; CHILD, PRESCHOOL; HUMANS; HYDRAZINES; INFANT; MAXIMUM TOLERATED DOSE; NEOPLASM RECURRENCE, LOCAL; SULFONAMIDES;

EID: 39749201673     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-07-4242     Document Type: Article

References (22)

1. Finch RA, Shyam K, Penketh PG, Sartorelli AC. 1,2-Bis(methylsulfonyl)-1- (2-chloroethyl)-2-(methylamino) carbonylhydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity. Cancer Res 2001;61:3033-8.
2. Penketh PG, Shyam K, Baumann RP, Remack JS, Brent TP, Sartorelli AC. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition. Cancer Chemother Pharmacol 2004;53:279-87.
3. Badruddoja MA, Penne K, Desjardins A, et al. Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme. Neuro-oncol 2007;9:70-4.
4. Giles F, Rizzieri D, Karp J, et al. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol 2007;25:25-31.
5. Giles F, Verstovsek S, Faderl S, et al. A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia. Leuk Res 2006;30:1591-5.
6. Giles F, Verstovsek S, Thomas D, et al. Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clin Cancer Res 2005;11:7817-24.
7. Giles F, Vey N, O'Brien S, et al. Phase II study of VNP40101M(VNP40101M) in patients (pts) with acute myelogenous leukemia (AML) and high risk myelodysplasia (MDS; abstr# 6541). Proc Am Soc Clin Oncol 2005;23:6541.
8. Murren J, Modiano M, Kummar S, et al. A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer. Invest New Drugs 2005;23:123-35.
9. Giles F, Thomas D, Garcia-Manero G, et al. A phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia. Clin Cancer Res 2004;10:2908-17.
10. Badruddoja MA, Keir ST, King I, et al. Activity of VNP40101M(Cloretazine) in the treatment of CNS tumor xenografts in athymic mice. Neuro-oncol 2007;9:240-4.
11. Piantadosi S, Fisher JD, Grossman S. Practical implementation of a modified continual reassessment method for dose-finding trials. Cancer Chemother Pharmacol 1998;41:429-36.
12. Krishna G, Hodnick WF, Lang W, et al. Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M. AAPS Pharm Sci Tech 2001;2:E14.
13. Macdonald DR, Cascino TL, Schold SC, Jr., Cairn-cross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277-80.
14. Bai F, Minkin P, Fraga CH, O'Shaughnessy MA, Gururangan S, Stewart CF. Determination of Cloretazinetrade mark (VNP40101M) and its active metabolite (VNP4090CE) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci 2007;853:97-104.
15. D'Argenio DZ, Schumitzky A. ADAPT IIUser's Guide. 1st ed. USC, Los Angeles; 1990.
16. Penketh PG, Shyam K, Sartorelli AC. Comparison of DNA lesions produced by tumor-inhibitory 1,2-bis-(sulfonyl)hydrazines and chloroethylnitrosoureas. Biochem Pharmacol 2000;59:283-91.
17. Schacht RG, Feiner HD, Gallo GR, Lieberman A, Baldwin DS. Nephrotoxicity of nitrosoureas. Cancer 1981;48:1328-34.
18. Zakarija A, Bennett C. Drug-induced thrombotic microangiopathy. Semin Thromb Hemost 2005;31:681-90.
19. Lee KC, Almassian B, Noveroske J. Toxicological evaluation of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylaminocarbonyl)hydrazine (VNP40101M), a novel alkylating agent with potential antitumor activity, with intravenous administration in rats and dogs. Int J Toxicol 2002;21:23-38.
20. Ishiguro K, Shyam K, Penketh PG, Sartorelli AC. Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine. Mol Cancer Ther 2005;4:1755-63.
21. Ishiguro KK, Seow HAHA, Penketh PGPG, Shyam KK, Sartorelli ACAC. Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine. Mol Cancer Ther 2006;5:969-76.
22. Spiro TP, Liu L, Majka S, Haaga J, Willson JK, Gerson SL. Temozolomide: the effect of once- and twice-a-day dosing on tumor tissue levels of the DNA repair protein O(6)-alkylguanine-DNA-alkyltransferase. Clin Cancer Res 2001;7:2309-17.