Clinical trials of O-diazoacetyl-L-serine (azaserine) in neoplastic disease

Phase I evaluation of AT-125 single dose every three weeks

“…Neurotoxicity consisting of temporary recent memory loss and blurring of vision has been reported with DON but is infrequent and not dose limiting (9). Nine of forty-one adults treated with azaserine had suspicious evidence of systemic intoxication manifested by apathy, confusion, possibly hypotension, and electrolyte abnormalities (10). Neurotoxicity has not been reported with azotomycin.…”

The Chemotherapy of Malignant Disease

“…13) (Hitchings et al, 1952) much the same fashion as the 4-amino derivatives of P.G.A., although probably at a different level. They are too toxic for therapeutic use (Murphy et al, 1954). A closely related drug, diaprim, originally introduced as an antimalarial, has been found useful in the control of polycythaemia vera (Frost and Jones, 1954).…”

“…The ultimate appearance of drug resistance in leukaemia, at first responding to folic acid antagonists, is invariable; when the disease becomes refractory to methotrexate, cIossresistance to all other folic antagonists, including D.D.M.P.. develops (Murphy et al, 1954).…”

“…15), an antibiotic derived from a Streptomyces, acts as a glutamine antagonist (Hartman et al, 1955). with acute leukaemia (Ellison et al, 1954), and there is a suggestion that, used concurrently with 6-M.P., it may increase the frequency of satisfactory response. This possible synergistic effect is under investigation at present.…”

Toxicity and Clinical Trial of Azaserine and 6-Thioguanine in Advanced Solid Malignant Neoplasms

“…AZASERINE alone was found to be ineffective in a limited spectrum of human solid tumors, except for short term improvement in 5 out of 44 trials in Hodgkin's disease (Ellison et al, 1954). Six-thioguanine used alone in leukemia was found to be somewhat more toxic and less effective than 6-mercaptopurine (Hales et al, 1957).…”