Activity of novel cytotoxic agents in lung cancer: epothilones and topoisomerase I inhibitors.

Abstract:

:The treatment of lung cancer--small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC)--is a significant challenge in oncology. The best reported median survival remains near 1 year in advanced NSCLC despite several decades of steady improvement and extensive research with traditional chemotherapy drugs and novel compounds targeted to different aspects of tumor cell growth and function (such as the epidermal growth factor receptor). Extensive-stage SCLC survival is only slightly better. Novel "targeted" therapeutic agents hold promise, but cytotoxic therapy remains the backbone of treatment. Many new cytotoxic agents are currently in development. In this review, we will focus on 2 classes of cytotoxins: epothilones and topoisomerase I inhibitors. Epothilones are microtubule stabilizers with a mechanism of action similar to that of the taxanes, with preclinical activity superior to that of the taxanes. Phase I trials have been completed for patupilone and ixabepilone, and there are encouraging phase II data with ixabepilone in NSCLC. A phase II trial of patupilone is ongoing. The camptothecins, which are topoisomerase I inhibitors, have a long history in the treatment of lung cancer, but the currently available drugs, topotecan and irinotecan, have limitations. Gimatecan and other novel camptothecins have superior preclinical activity and promising phase I/II data in NSCLC and SCLC.

journal_name

Clin Lung Cancer

journal_title

Clinical lung cancer

authors

Wakelee HA,Sikic BI

doi

10.3816/clc.2005.s.002

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

S6-12

eissn

1525-7304

issn

1938-0690

pii

S1525-7304(11)70418-1

journal_volume

7 Suppl 1

pub_type

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