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Preclinical evaluation of the homo-aza-steroid ester 13beta-hydroxy-13alpha-amino-13,17- seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)aminophenoxy acetate for the treatment of malignant melanoma.

PURPOSE
To investigate the in vitro and in vivo activity of an homo-aza-steroid alkylating ester, namely 13beta-hydroxy- 13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17- lactam-p-bis (2-chloro ethyl) aminophenoxy acetate (HASE), in comparison with dacarbazine (DTIC) in the treatment of malignant melanoma.


MATERIALS AND METHODS
Cytotoxicity was assessed in vitro by the MTT assay using a panel of 6 malignant melanoma human cell lines, with or without the presence of rat liver microsome assay. B16 melanoma-bearing mice were used to evaluate in vivo the antitumor activity of the tested compounds.


RESULTS
In all cases of in vitro screening, HASE displayed significantly higher (p <0.0001) cytostatic and cytotoxic activity than DTIC. Moreover, the antitumor activity of HASE in B16 melanoma-bearing mice was satisfactory, prolonging the mice lifespan at 67%, compared to 43% achieved by DTIC. Furthermore, HASE significantly inhibited the tumor growth (tumor growth rate: <42%) as this was defined by tumor volume and weight differences, presenting higher antitumor effect than DTIC.


CONCLUSION
HASE displayed superior in vitro and in vivo activity than DTIC in the treatment of melanoma. Thus, HASE may be considered as a significant candidate anticancer agent for further development.