In vitro and in vivo potentiation by lonidamine of the antitumor effect of adriamycin.

Lonidamine (LND), a powerful antispermatogenic compound, has been shown to impair differentially the energy metabolism of normal and neoplastic cells and to increase significantly the survival of animal bearing experimental tumors. Clinical trials are presently ongoing and preliminary favourable results have been obtained with LND as a single agent or associated with other antineoplastic drugs. In this work the effect of the combination LND plus ADM was investigated on in vitro and in vivo tumors. The in vitro effect was analysed by the colony forming technique and the in vivo antitumor activity was assessed by means of local control parameters, increase in host lifespan and weight reduction of metastasing target organs (liver, kidney, ovary). The results obtained indicate that LND is poorly effective when used alone, while a very high cytotoxicity is observed when it is combined with ADM. Exposure of cells to different time-sequences and schedules of both drugs elicits a different response. In particular a synergistic effect is obtained when ADM precedes LND. These results have been preliminarily confirmed by in vivo studies.