ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A 
nonrandomized phase 1 dose-escalation study of ABT-751 in combination with 
CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the 
maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in 
patients with advanced colorectal cancer. Patients were treated with ABT-751 
daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 
daily and capecitabine twice daily for 14 days plus irinotecan on day 1 
intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 
after the first 2 dose levels. Because of intolerance to the regimen, a reduced 
dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with 
bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, 
and protein binding were explored. Twenty-four patients were treated over 5 dose 
levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose 
CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver 
tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser 
extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 
exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically 
relevant alterations in ABT-751 and irinotecan pharmacokinetics were not 
observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and 
bevacizumab will not be studied further in colorectal cancer.