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3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

Abstract：

:3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

authors

Margolin K,Doroshow J,Leong L,Akman S,Carr B,Odujinrin O,Flanagan B,Grove W,DeLap R,Goldberg D

doi

10.1007/BF00198593

subject

Has Abstract

pub_date

1990-11-01 00:00:00

pages

369-76

issue

4

eissn

0167-6997

issn

1573-0646

journal_volume

8

pub_type

临床试验,杂志文章

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