Combination therapy with SCH58500 (p53 adenovirus) and cyclophosphamide inpreclinical cancer models

SCH58500 (ACN53) is a replication-deficient, recombinant adenovirus which e xpresses human p53 tumor suppressor. In preclinical models, SCH58500 has th erapeutic efficacy against a wide range of human tumor types containing non functional p53 and it has enhanced activity in combination with many chemot herapeutic drugs. However, the anti-tumor efficacy of SCH58500 combined wit h the DNA-damaging chemotherapeutic cyclophosphamide has not been previousl y reported. Cyclophosphamide did not enhance the activity of SCH58500 in th ree out of four human tumor xenograft models studied; Furthermore, combinat ion therapy with SCH58500 and cyclophosphamide was not any better than sing le drug treatment in transgenic H-ras mice and in FVB mice bearing syngenei c MidT2-1 tumors. This is in sharp contrast to previous combination studies in these models where SCH58500 had enhanced efficacy when given with the f arnesyl protein transferase inhibitor SCH66336, paclitaxel, cisplatin, cisp latin/paclitaxel, or doxorubicin. Further evaluation of this combination is required before it can be recommended for clinical trials in cancer patien ts.