STEALTH® Liposomal CKD-602, a Topoisomerase I Inhibitor, Improves the Therapeutic Index in Human Tumor Xenograft Models

Abstract

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.