Linked Life Data

1671875

Source:http://linkedlifedata.com/resource/pubmed/id/1671875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-4-9
pubmed:abstractText
To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0732-183X
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
416-22
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
A phase I clinical trial of 2-chlorodeoxyadenosine in pediatric patients with acute leukemia.
pubmed:affiliation
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38101.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Controlled Clinical Trial, Research Support, Non-U.S. Gov't