STEALTH liposomal CKD-602, a topoisomerase I inhibitor, improves the therapeutic index in human tumor xenograft models.
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.


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 approximately 6-fold greater than that of free CKD-602 in ES-2 and approximately 3-fold greater in H82 tumors. TI of S-CKD602 was approximately 2-fold greater than that of free CKD-602 and approximately 5-fold greater than that of topotecan in A375, and > or = 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.


CONCLUSIONS
The therapeutic index of S-CKD602 was greater than that of free CKD-602 and topotecan in several human tumor types.
Yu
Ning Y
NY
ALZA Corporation, 1900 Charleston Road M3A, Mountain View, CA 94043-7210, USA. nyu2@alzus.jnj.com
Conway
Colleen
C
Pena
Rhoneil L S
RL
Chen
Joy Y
JY
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000201:enzymology; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D059005:Topoisomerase II Inhibitors; D019772:Topotecan / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D008081:Liposomes; D059005:Topoisomerase II Inhibitors; C116963:belotecan; D019772:Topotecan; D002166:Camptothecin