caa a22 4500 465789927 CHVBK 20180323112020.0 cr unu---uuuuu 170327e19901101xx s 000 0 eng 10.1007/BF00198593 doi (NATIONALLICENCE)springer-10.1007/BF00198593 3-Deazaguanine: Report of a phase I trial and drug-related cardiac toxicity [Elektronische Daten] [Kim Margolin, James Doroshow, Lucille Leong, Steven Akman, Brian Carr, Oluwole Odujinrin, Bridget Flanagan, William Grove, Robert DeLap, David Goldberg] Summary: 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. Kluwer Academic Publishers, 1990 3-deazaguanine nationallicence dezaguanine nationallicence phase I nationallicence cardiotoxicity nationallicence Margolin Kim Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Doroshow James Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, MI48105, Ann Arbor, USA aut Leong Lucille Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Akman Steven Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Carr Brian Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Odujinrin Oluwole Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Flanagan Bridget Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut Grove William Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, MI48105, Ann Arbor, USA aut DeLap Robert Clinical Development, LederleLabs, 10965, Pearl River, NY, USA aut Goldberg David 5667 Peachtree Dunwoody Rd., Suite 285, 30342, Atlanta, G A, USA aut Investigational New Drugs Kluwer Academic Publishers 8/4(1990-11-01), 369-376 0167-6997 8:4<369 1990 8 10637 https://doi.org/10.1007/BF00198593 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00198593 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Margolin Kim Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Doroshow James Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, MI48105, Ann Arbor, USA aut NATIONALLICENCE 700 1- Leong Lucille Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Akman Steven Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Carr Brian Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Odujinrin Oluwole Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Flanagan Bridget Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, 91010, Duarte, CA, USA aut NATIONALLICENCE 700 1- Grove William Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, MI48105, Ann Arbor, USA aut NATIONALLICENCE 700 1- DeLap Robert Clinical Development, LederleLabs, 10965, Pearl River, NY, USA aut NATIONALLICENCE 700 1- Goldberg David 5667 Peachtree Dunwoody Rd., Suite 285, 30342, Atlanta, G A, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/4(1990-11-01), 369-376 0167-6997 8:4<369 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer