Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study.

Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study. Research Abstract Details 

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Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study. Abstract Text:

Sridharan Gururangan,Christopher D Turner,Clinton F Stewart,Melinda O'Shaughnessy,Mehmet Kocak,Tina Young Poussaint,Peter C Phillips,Stewart Goldman,Roger Packer,Ian F Pollack,Susan M Blaney,Verena Karsten,Stanton L Gerson,James M Boyett,Henry S Friedman,Larry E Kun,

PURPOSE: VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors. EXPERIMENTAL DESIGN: VNP40101M was given i.v. daily for 5 consecutive days every 6 weeks for up to eight cycles. Dose escalation was done independently in patients stratified based on intensity of prior therapy (moderately pretreated, stratum I; heavily pretreated, stratum II). Correlative studies included pharmacokinetics and measurement of O(6)-alkylguanine-DNA alkyl transferase levels in peripheral blood mononuclear cells before and after treatment. RESULTS: Forty-one eligible patients (stratum I, 19; stratum II, 22) were enrolled on this study. The dose-limiting toxicity in 35 evaluable patients was myelosuppression, which occurred in 4 of 16 patients in stratum I and 3 of 19 patients in stratum II. Pharmacokinetic studies showed a median terminal half-life of 30 min (range, 14-39.5). The maximum tolerated dose in stratum I and II were 45 and 30 mg/m(2)/d daily for 5 days every 6 weeks, respectively. Peripheral blood mononuclear cells alkylguanine alkyl transferase levels did not decrease significantly after VNP40101M treatment. Central imaging review confirmed that three patients had stable disease for a median of 45 weeks (range, 37-61+) after therapy. CONCLUSIONS: The recommended dose of VNP40101M for phase II studies in children with brain tumors is 45 mg/m(2)/d in moderately pretreated and 30 mg/m(2)/d in heavily pretreated patients when administered for 5 consecutive days every 6 weeks.

Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study. Publishing Authors By Initials

S Gururangan,CD Turner,CF Stewart,M O'Shaughnessy,M Kocak,TY Poussaint,PC Phillips,S Goldman,R Packer,IF Pollack,SM Blaney,V Karsten,SL Gerson,JM Boyett,HS Friedman,LE Kun,

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Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 14

Page Numbers: 1124-30

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Feb

YEAR: 2008

Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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AFFILIATION: Authors' Affiliations: The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina.

Country: United States

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MEDLINETA: Clin Cancer Res

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