A new steroidal alkylating agent with improved activity in advanced murine leukemias

Abstract

The homo-aza-steroidal ester of [p-[bis(2-chloroethyl)amino]phenoxy] acetic acid, 3 beta-hydroxy 13 alpha - amino - 13,17 - seco - 5 alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)aminophenoxyacetate, gave a 100% increase in lifespan over controls in the treatment of L1210 leukemia by IP administration on a days 1 and 4 treatment schedule. This ester gave a maximum activity of 383% increased lifespan over controls in the treatment of P388 leukemia by IP administration on a daily treatment schedule. Activity in advanced L1210 (41% increased lifespan) and P388 leukemias (173% increased lifespan) was maintained, indicating that this compound is the most promising of a number of congeners tested to date.

Lactandrate: a D-homo-aza-androsterone alkylator in the treatment of breast cancer

“…The designing of homo-aza-(lactam) steroids, that contain -NH-CO-group inside the A or D steroid nucleus, as biological carriers for carboxylic derivatives of N,N-bis(2-chloroethyl) aniline (nitrogen mustards) based on the evidence that these esters are highly active against murine leukemia [3][4][5] and rodent solid tumor systems including human xenografts [5][6][7]. Most of the unmodified steroid alkylators have been inactive in murine L1210 lymphoid and in P388 lymphocytic leukemia, while the respective homo-aza-steroid esters, produced excellent results in these leukemia systems [8,9].…”

Comparison of Current Alkylating Agents with a Homo-aza-Steroidal Ester for Antineoplastic Activity

“…The hybrid steroidal lactam of the A-and D-ring of the steroid nucleus with carboxylic derivatives of N,N-bis(2-chloroethyl)aniline esterified at C-17 or C-3, respectively, produces active compounds in solid tumors [1][2][3] and in P388 and LI 210 leukemias [4][5][6][7], while unmodified ste roidal esters are inactive in LI 210 leukemia [8].…”

Activity of 13β–Hydroxy–13α–amino–13,17-seco– 5α–androstan–17–oic–13,17–lactam–p–bis(2–chloro–ethyl)aminophenoxyacetate (NSC 294859) on Experimental Animal Tumor and Leukemia Systems

“…This agent has good activity in L1210 and P388 leukemias with maintenance of activity against the advanced tumors [6], Since the activity in these tumors appeared promising, studies were extended to other murine tumors. Assuming hydrolysis in biologic sys tems this ester would be transformed to the wellknown antitumor aniline derivative, /?-di-2-chloroethylaminophenol.…”

“…results]. These compounds have shown antitumor activity in most tumors tested re gardless of whether they originated in endocrinesensitive tumors or not [2][3][4][5][6]8],…”