Ixabepilone

Biological Activity

Ixabepilone (BMS 247550) is an epothilone B analog and nontaxane microtubule-stabilizing compound. Ixabepilone induces cell cycle arrest at the G(2)-M phase transition and subsequent apoptotic cell death of MDA-MB-468 (468) cells. Ixabepilone, on a once every 21-day schedule, is modestly active against metastatic gastric cancer previously treated with a taxane. The days 1-5 every 21 days schedule had a more favorable safety profile but no activity. The results of this study suggest that once every 21-day ixabepilone schedule should be pursued further in untreated gastric or gastroesophageal adenocarcinoma patients. Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy.
Kim YH, et al. Cancer Chemother Pharmacol. 2012 Oct;70(4):583-90. PMID: 22886073.

A phase I study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer.
Roché H, et al. Clin Breast Cancer. 2012 Jun;12(3):167-74. PMID: 22607766.

A phase II clinical trial of ixabepilone (Ixempra; BMS-247550; NSC 710428), an epothilone B analog, in patients with metastatic renal cell carcinoma.
Huang H, et al. Clin Cancer Res. 2010 Mar 1;16(5):1634-41. PMID: 20179242.