Phase I trial of tallysomycin S10b, a bleomycin analogue.
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 beta half-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, rectal cancer and lung cancer. 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.
Division of Hematology-Oncology, SUNY Health Science Center, Syracuse 13210.
F P
FP
Paolozzi
R C
RC
Gaver
N B
NB
Newman
B J
BJ
Poiesz
S
S
DeFino
A
A
Louie
R L
RL
Comis
D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D001761:Bleomycin; C016126:talisomycin