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Research ArticleExperimental Studies

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

NING Y. YU, COLLEEN CONWAY, RHONEIL L.S. PENA and JOY Y. CHEN
Anticancer Research July 2007, 27 (4B) 2541-2545;
NING Y. YU
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  • For correspondence: nyu2@alzus.jnj.com
COLLEEN CONWAY
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RHONEIL L.S. PENA
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JOY Y. CHEN
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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.

  • S-CKD602
  • camptothecin
  • therapeutic index
  • human tumor xenografts
  • STEALTH® liposomes
  • topotecan

Footnotes

    • Received March 23, 2007.
    • Revision received June 8, 2007.
    • Accepted June 12, 2007.
    • Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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    Anticancer Research: 27 (4B)
    Anticancer Research
    Vol. 27, Issue 4B
    July-August 2007
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    STEALTH® Liposomal CKD-602, a Topoisomerase I Inhibitor, Improves the Therapeutic Index in Human Tumor Xenograft Models
    NING Y. YU, COLLEEN CONWAY, RHONEIL L.S. PENA, JOY Y. CHEN
    Anticancer Research Jul 2007, 27 (4B) 2541-2545;

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    STEALTH® Liposomal CKD-602, a Topoisomerase I Inhibitor, Improves the Therapeutic Index in Human Tumor Xenograft Models
    NING Y. YU, COLLEEN CONWAY, RHONEIL L.S. PENA, JOY Y. CHEN
    Anticancer Research Jul 2007, 27 (4B) 2541-2545;
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