caa a22 4500 465789412 CHVBK 20180323112019.0 cr unu---uuuuu 170327e19900201xx s 000 0 eng 10.1007/BF00216922 doi (NATIONALLICENCE)springer-10.1007/BF00216922 Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog [Elektronische Daten] [Robert Newman, Zahid Siddik, Elizabeth Travis, David Followill, Workenesh Ayele, Tim Burditt, Irwin Krakoff] Summary: The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1-10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Kluwer Academic Publishers, 1990 liblomycin nationallicence bleomycin nationallicence pulmonary and hematologic toxicities nationallicence Newman Robert Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Siddik Zahid Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Travis Elizabeth Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Followill David Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Ayele Workenesh Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Burditt Tim Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Krakoff Irwin Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut Investigational New Drugs Kluwer Academic Publishers 8/1(1990-02-01), 33-41 0167-6997 8:1<33 1990 8 10637 https://doi.org/10.1007/BF00216922 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00216922 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Newman Robert Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Siddik Zahid Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Travis Elizabeth Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Followill David Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Ayele Workenesh Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Burditt Tim Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Krakoff Irwin Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/1(1990-02-01), 33-41 0167-6997 8:1<33 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer