Accomplishments:1. Determination of genes associated with erlotinib treatment and EGFR positive: G-protein linked and cell surface receptor linked signaling.2. Ixabepilone is an effective drug in both taxane-nave and taxane-pretreated populations when given daily for 5 days every 3 weeks. 3. Ixabepilone given for 3 days every 3 weeks in the taxane-nave population is not an effective regimen. 4. Grooved Pegboard Test and the Jebsen Test of Hand Function are associated with the development of neuropathy over time after treatment with ixabepilone. 5. Increase in acetylation of a-tubulin was noted after treatment with ixabepilone in all patients whose tumors were available for evaluation. These findings suggest evidence of the drug reaching the target, and warrant further study to predict response in a larger population.6. Garlic does not significantly affect the disposition of docetaxel.7. A Pertuzumab and trastuzumab study was designed, implemented, and is ongoing.8. Tipifarnib (200 mg BID for 21 of 28 days) and tamoxifen (20 mg QD) can be administered safely with minimal toxicity.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010435-06
Application #
7338524
Study Section
(MOB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Denduluri, Neelima; Lee, James J; Walshe, Janice et al. (2007) Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every three weeks, in metastatic breast cancer. Invest New Drugs 25:63-7
Walshe, Janice M; Denduluri, Neelima; Berman, Arlene W et al. (2006) A phase II trial with trastuzumab and pertuzumab in patients with HER2-overexpressed locally advanced and metastatic breast cancer. Clin Breast Cancer 6:535-9
Lee, James J; Low, Jennifer A; Croarkin, Earllaine et al. (2006) Changes in neurologic function tests may predict neurotoxicity caused by ixabepilone. J Clin Oncol 24:2084-91
Low, Jennifer A; Wedam, Suparna B; Lee, James J et al. (2005) Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol 23:2726-34