RT Journal Article
SR Electronic
T1 STEALTH® Liposomal CKD-602, a Topoisomerase I Inhibitor, Improves the Therapeutic Index in Human Tumor Xenograft Models
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2541
OP 2545
VO 27
IS 4B
A1 NING Y. YU
A1 COLLEEN CONWAY
A1 RHONEIL L.S. PENA
A1 JOY Y. CHEN
YR 2007
UL http://ar.iiarjournals.org/content/27/4B/2541.abstract
AB Background: CKD-602, a topoisomerase I inhibitor, has antitumor activity in a broad spectrum of tumor types. STEALTH® liposomal CKD-602 (S-CKD602) prolongs circulation of CKD-602 in plasma, increases drug exposure in tumors and improves efficacy compared with free drug. Materials and Methods: Different dosing regimens of S-CKD602, free CKD-602 and topotecan were compared for antitumor activity in female athymic nude mice bearing human A375 melanoma, ES-2 ovarian, H82 SCLC or HT-29 colon tumor xenografts. Results: S-CKD602 was more efficacious than free drug in all tumor types studied. The therapeutic index (TI) of S-CKD602 was estimated to be ~6-fold greater than that of free CKD-602 in ES-2 and ~3-fold greater in H82 tumors. TI of S-CKD602 was ~2-fold greater than that of free CKD-602 and ~5-fold greater than that of topotecan in A375, and ≥3-fold greater in HT-29 tumors. In A375 tumors, once-weekly dosing of S-CKD602 was superior to once every 2 weeks or twice weekly schedules. Conclusion: The therapeutic index of S-CKD602 was greater than that of free CKD-602 and topotecan in several human tumor types. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved