Annals of Oncology Advance Access published online on July 24, 2009
Annals of Oncology, doi:10.1093/annonc/mdp311
A phase IB study of ABT-751 in combination with docetaxel in patients with advanced castration-resistant prostate cancer
1 Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, Vancouver
2 Department of Medical Oncology, Vancouver Island Centre, British Columbia Cancer Agency, Victoria
3 Department of Medical Oncology, Southern Interior Centre, British Columbia Cancer Agency, Kelowna
4 Department of Medical Oncology, Fraser Valley Centre, British Columbia Cancer Agency, Surrey
5 The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada
6 Abbott Laboratories, Abbott Park, IL, USA
* Correspondence to: Dr K. N. Chi, Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. Tel: +1-604-877-6000; Fax: +1-604-877-0585; E-mail: k.chi{at}bccancer.bc.ca
Background: This study investigated the safety, pharmacokinetics (PK) and clinical antitumor activity of ABT-751, a novel sulfonamide antimitotic and vascular disrupting agent, in combination with docetaxel (Taxotere) in patients with castration-resistant prostate cancer (CRPC).
Patients and methods: Patients received docetaxel (60–75 mg/m2) i.v. on day 1 and ABT-751 (100–200 mg) orally daily for 14 days, repeated every 3 weeks for up to 10 times on four escalating dose levels (DLs).
Results: Thirty-two patients received a median of 8.5 treatment cycles (range 1–10). One of six patients on DL 3 (D 60 mg/m2 + A 200 mg) and 4 (D 75 mg/m2 + A 200 mg) experienced dose-limiting toxicity, and both DLs were expanded. Overall, severe adverse events occurred more commonly on DL 4 than 3 (47% versus 18% of patients). PK data for docetaxel and ABT-751 were similar to reported literature. Best post-treatment prostate-specific antigen decline of 
50% occurred in 60% and objective responses occurred in 45% of patients. Median overall survival was 24 months (95% confidence interval 8.3–37.7 months).
Conclusions: The combination of ABT-751 and docetaxel is safe and active in CRPC. Based on the cumulative safety analysis, the recommended phase II dose of ABT-751 is 200 mg daily with docetaxel 60 mg/m2 for this patient population.
ABT-751, chemotherapy, docetaxel, prostate cancer
Received for publication February 2, 2009. Revision received April 15, 2009. Accepted for publication May 12, 2009.