STEALTH liposomal CKD-602, a topoisomerase I inhibitor, improves the therapeutic index in human tumor xenograft models
Yu, N.Y.; Conway, C.; Pena, R.L.S.; Chen, J.Y.
Anticancer Research 27(4B): 2541-2545
2007
ISSN/ISBN: 0250-7005 PMID: 17695551 Document Number: 605520
Background: CKD-602, a topoisomerase I inhibitor, has antitumor activity in a broad spectrum of tumor types. STEALTH (R) liposomal CKD-602 (S-CKD602) prolongs circulation of CK-D-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 beating 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 similar to 6-fold greater than that of free CKD-602 in ES-2 and similar to 3-fold greater in H82 tumors. TI of S-CKD602 was similar to 2-fold greater than that of free CKD-602 and similar to 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.