caa a22 4500 465790127 CHVBK 20180323112021.0 cr unu---uuuuu 170327e19900501xx s 000 0 eng 10.1007/BF00177253 doi (NATIONALLICENCE)springer-10.1007/BF00177253 Phase I trial of tallysomycin S10b, a bleomycin analogue [Elektronische Daten] [Frank Paolozzi, Robert Gaver, Nancy Newman, Bernard Poiesz, Santo DeFino, Arthur Louie, Robert Comis] Summary: Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose-or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 βhalf-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma [2], rectal cancer [1] and lung cancer [1]. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma. Kluwer Academic Publishers, 1990 tallysomycin S10b nationallicence bleomycin analogues nationallicence chemotherapy-induced lung toxicity nationallicence Paolozzi Frank Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut Gaver Robert Pharmaceutical Research and Development Division, Bristol-Myers Company, 13221, Syracuse, NY, USA aut Newman Nancy Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut Poiesz Bernard Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut DeFino Santo Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut Louie Arthur Pharmaceutical Research and Development Division, Bristol-Myers Company, 13221, Syracuse, NY, USA aut Comis Robert Fox-Chase Cancer Center, 7701 Burholme Ave., 19111, Philadelphia, PA, USA aut Investigational New Drugs Kluwer Academic Publishers 8/2(1990-05-01), 171-180 0167-6997 8:2<171 1990 8 10637 https://doi.org/10.1007/BF00177253 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00177253 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Paolozzi Frank Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Gaver Robert Pharmaceutical Research and Development Division, Bristol-Myers Company, 13221, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Newman Nancy Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Poiesz Bernard Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut NATIONALLICENCE 700 1- DeFino Santo Division of Hematology-Oncology, SUNY Health Science Center, 750 E. Adams Street, 13210, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Louie Arthur Pharmaceutical Research and Development Division, Bristol-Myers Company, 13221, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Comis Robert Fox-Chase Cancer Center, 7701 Burholme Ave., 19111, Philadelphia, PA, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/2(1990-05-01), 171-180 0167-6997 8:2<171 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer