Modulation of the toxicity and antitumour activity of alkylating drugs by steroids

Abstract

The steroids prednisolone and progesterone significantly altered the therapeutic indices of the alkylating agents, nitrogen mustard, melphalan, cyclophosphamide, phenyl acetic mustard and chlorambucil. For nitrogen mustard, chlorambucil and phenyl acetic mustard, prednisolone reduced host toxicity in the rat and enhanced the antitumour effectiveness against alkylating-agent-resistant strains of the Yoshida sarcoma and Walker carcinosarcoma. Progesterone also increased the therapeutic index of chlorambucil in the rat by decreasing its systemic toxicity. Two other alkylating agents, melphalan and cyclophosphamide, exhibited lower therapeutic indices in combination with prednisolone against alkylating-agent-sensitive tumours. This was due to the greater host toxicity of the combination than of the alkylating agent alone. In alkylating-agent-resistant tumours, however, a significant increase in growth delay was achieved if prednisolone was combined with the alkylating agent.