Relation between 9-aminocamptothecin systemic exposure and tumor response in human solid tumor xenografts

M. N. Kirstein, P. J. Houghton, P. J. Cheshire, L. B. Richmond, A. K. Smith, S. K. Hanna, C. F. Stewart

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

9-Aminocamptothecin (9-AC) is a topoisomerase I inhibitor with activity against xenografts from childhood solid tumors; however, clinical trials with this compound have been disappointing, resulting in discontinuation of further development. The objectives of this study were to evaluate the antitumor activity of 9-AC in a panel of pediatric solid tumor xenografts and to relate the 9-AC lactone systemic exposure, defined as area under the concentration time curve (AUC), to the antitumor dose associated with tumor regression in the xenograft model. We evaluated protracted administration of i.v. and oral therapies (daily times 5) for 1,2, or 3 weeks and for 1 or 3 cycles. The minimum effective dose of 9-AC causing objective regression of advanced tumors was determined for each schedule. 9-AC lactone plasma concentration-time profiles associated with the lowest dose achieving complete and partial responses for each xenograft were then determined for each regimen. Tumors were highly sensitive to 9-AC therapy, but the systemic exposure required for antitumor effect is in excess of that achievable in patients.

Original languageEnglish (US)
Pages (from-to)358-366
Number of pages9
JournalClinical Cancer Research
Volume7
Issue number2
StatePublished - 2001

Fingerprint Dive into the research topics of 'Relation between 9-aminocamptothecin systemic exposure and tumor response in human solid tumor xenografts'. Together they form a unique fingerprint.

Cite this