A phase II clinical trial of ixabepilone (Ixempra; BMS-247550; NSC 710428), an epothilone B analog, in patients with metastatic renal cell carcinoma.
OBJECTIVE
Ixabepilone (Ixempra; BMS-247550) is an epothilone B analog and nontaxane microtubule-stabilizing compound with clinical activity in a range of solid tumors. This phase II study was conducted to assess the efficacy and safety of ixabepilone in patients with metastatic renal cell carcinoma.


METHODS
Patients with metastatic renal cell carcinoma who had measurable disease and had not received previous cytotoxic or targeted therapy were treated with 6 mg/m(2) ixabepilone i.v. daily for 5 days every 3 weeks. Levels of Glu-terminated and acetylated tubulin, markers of microtubule stabilization, were assessed by Western blot. VHL gene mutation status was determined by sequencing.


RESULTS
Eighty-seven patients received a total of 590 cycles, with a median of 5 cycles (range, 1-29). The overall response rate was 13% (Response Evaluation Criteria in Solid Tumor). One patient had a complete response, 10 patients had partial responses, and 59 patients had stable disease. The median duration of response was 5.5 months. The median overall survival of renal cell carcinoma Motzer grade 0 and 1 patients with clear cell histology was 19.25 months. Treatment-related adverse events were primarily alopecia, gastrointestinal toxicity, neuropathy, and fatigue. Biopsies were done at baseline and after five doses of ixabepilone. Microtubule target engagement was achieved in 84.6% to 92.3% of patients evaluated. No correlation was identified between the target engagement, VHL gene mutation status, and clinical response.


CONCLUSIONS
Ixabepilone can cause tumor regression in some patients with metastatic renal cell carcinoma and could be considered in combination regimens with other therapies.
Huang
Hui
H
Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Menefee
Michael
M
Edgerly
Maureen
M
Zhuang
Sen
S
Kotz
Herb
H
Poruchynsky
Marianne
M
Huff
Lyn Mickley
LM
Bates
Susan
S
Fojo
Tito
T
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014404:Tubulin / Q000187:drug effects
D000970:Antineoplastic Agents; D034261:Epothilones; D014404:Tubulin; C430592:ixabepilone