TY - JOUR
T1 - Clinical experience with epothilones in patients with breast cancer
AU - Buzdar, Aman U.
N1 - Funding Information:
This article includes discussion of investigational and/or unlabeled uses of drugs, including ixabepilone for breast cancer in the neoadjuvant or adjuvant setting or for taxane-naive MBC; capecitabine with or without ixabepilone for anthracycline/taxane non-resistant MBC; ixabepilone plus trastuzumab or bevacizumab for advanced or MBC; and patupilone, ZK-EPO, BMS-310705, and KOS-862 in a variety of solid tumors. Dr Buzdar has received research support from Bristol-Myers Squibb, Genentech BioOncology, Pfizer, Eli Lilly, AstraZeneca, and Taiho Pharmaceuticals.
PY - 2008
Y1 - 2008
N2 - The search for novel chemotherapeutic agents in the treatment of breast cancer with lower susceptibility to resistance mechanisms than current agents has led to the discovery of the epothilones and their analogues. Epothilones stabilize microtubules in a manner similar to taxanes but are structurally distinct. Ixabepilone, an epothilone B analogue, having demonstrated high antimicrotubule activity in preclinical studies, has shown notable efficacy in phase II trials in patients with early-stage and metastatic breast cancer. Of particular note, single-agent ixabepilone is effective in tumors resistant to anthracyclines, taxanes, and capecitabine, for which there is currently no recommended therapy. Different mechanisms of action and the non-overlapping toxicities of ixabepilone with other agents provide the rationale for ixabepilone in combination as a valid therapeutic approach. Phase II results assessing ixabepilone in combination with capecitabine in anthracy-cline- and taxane-pretreated patients are promising. The investigation of ixabepilone in the neoadjuvant setting has also revealed potential biomarkers to predict ixabepilone response. Ixabepilone has demonstrated activity in patients with tumors that are estrogen receptor-, progesterone receptor-, and HER2-negative. The safety profile throughout the trials has been manageable, with peripheral neuropathy as one of the more notable adverse events, which has been mostly reversible. A phase III trial comparing ixabepilone plus capecitabine versus capecitabine alone demonstrated significant prolongation of median progression-free survival and reduction in relapse risk. Additionally, other members of the epothilone family, such as patupilone, ZK-EPO, BMS-310705, and KOS-862, have demonstrated efficacy against breast cancer in phase I clinical trials. Ongoing phase II/III trials continue to assess ixabepilone and other members of the epothilone family in breast cancer, particularly in combination regimens, as being valid treatment options in multidrug-resistant breast cancer.
AB - The search for novel chemotherapeutic agents in the treatment of breast cancer with lower susceptibility to resistance mechanisms than current agents has led to the discovery of the epothilones and their analogues. Epothilones stabilize microtubules in a manner similar to taxanes but are structurally distinct. Ixabepilone, an epothilone B analogue, having demonstrated high antimicrotubule activity in preclinical studies, has shown notable efficacy in phase II trials in patients with early-stage and metastatic breast cancer. Of particular note, single-agent ixabepilone is effective in tumors resistant to anthracyclines, taxanes, and capecitabine, for which there is currently no recommended therapy. Different mechanisms of action and the non-overlapping toxicities of ixabepilone with other agents provide the rationale for ixabepilone in combination as a valid therapeutic approach. Phase II results assessing ixabepilone in combination with capecitabine in anthracy-cline- and taxane-pretreated patients are promising. The investigation of ixabepilone in the neoadjuvant setting has also revealed potential biomarkers to predict ixabepilone response. Ixabepilone has demonstrated activity in patients with tumors that are estrogen receptor-, progesterone receptor-, and HER2-negative. The safety profile throughout the trials has been manageable, with peripheral neuropathy as one of the more notable adverse events, which has been mostly reversible. A phase III trial comparing ixabepilone plus capecitabine versus capecitabine alone demonstrated significant prolongation of median progression-free survival and reduction in relapse risk. Additionally, other members of the epothilone family, such as patupilone, ZK-EPO, BMS-310705, and KOS-862, have demonstrated efficacy against breast cancer in phase I clinical trials. Ongoing phase II/III trials continue to assess ixabepilone and other members of the epothilone family in breast cancer, particularly in combination regimens, as being valid treatment options in multidrug-resistant breast cancer.
KW - Antimicrotubule agents
KW - Ixabepilone
KW - P-glycoprotein
KW - Triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=52449115718&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52449115718&partnerID=8YFLogxK
U2 - 10.3816/CBC.2008.s.003
DO - 10.3816/CBC.2008.s.003
M3 - Article
C2 - 18637402
AN - SCOPUS:52449115718
SN - 1526-8209
VL - 8
SP - S71-S78
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - SUPPL. 2
ER -