In vitro activity of amonafide against primary human tumors compared with the activity of standard agents.
Amonafide, one of a series of benz[de]-isoquinoline-1,3-dione compounds, is now entering phase II clinical trials in this country. We tested amonafide, exposed continuously for 5 days, at four different concentrations against 56 primary human tumors in vitro. The drug concentration range used was based on amonafide's inhibitory activity against human bone marrow cells. The antitumor activity of 5-fluorouracil, mitomycin C, cisplatin, and etoposide against tumors from this panel of 56 was compared with that of amonafide at in vitro concentrations equitoxic against human bone marrow cells. Amonafide was active against only 12% of tumors compared with standard agents, which were active against more than 40% of tumors in the human bone marrow inhibitory range. Our data suggested that amonafide is less likely to be clinically active against human solid tumors than the standard agents.
Ajani
J A
JA
Department of Medical Oncology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Baker
F L
FL
Spitzer
G
G
D000225:Adenine; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007094:Imides; D007546:Isoquinolines / Q000494:pharmacology*; D053644:Naphthalimides; D063065:Organophosphonates; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; D000225:Adenine