Chloroquinoxaline sulfonamide: a sulfanilamide antitumor agent entering clinical trials.
Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame. The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45-132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans. Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2.
Fisherman
J S
JS
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda.
Osborn
B L
BL
Chun
H G
HG
Plowman
J
J
Smith
A C
AC
Christian
M C
MC
Zaharko
D S
DS
Shoemaker
R H
RH
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D011810:Quinoxalines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013424:Sulfanilamides / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D011810:Quinoxalines; D013424:Sulfanilamides; C048021:5-chloroquinoxaline-2-sulfanilamide