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

Authors
Citation
Ll. Nielsen, Combination therapy with SCH58500 (p53 adenovirus) and cyclophosphamide inpreclinical cancer models, ONCOL REP, 7(6), 2000, pp. 1191-1196
Citations number
23
Categorie Soggetti
Oncology
Journal title
ONCOLOGY REPORTS
ISSN journal
1021335X → ACNP
Volume
7
Issue
6
Year of publication
2000
Pages
1191 - 1196
Database
ISI
SICI code
1021-335X(200011/12)7:6<1191:CTWS(A>2.0.ZU;2-D
Abstract
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.