Journal article

Ongoing phase I studies of ABT-263: Mitigating Bcl-XL induced thrombocytopenia with lead-in and continuous dosing

AW Roberts, W Wilson, L Gandhi, OA O'Connor, CM Rudin, JR Brown, H Xiong, Y Chiu, S Enschede, AP Krivoshik

Journal of Clinical Oncology | American Society of Clinical Oncology (ASCO) | Published : 2009

Abstract

3505 Background: ABT-263, a novel, oral BH3 mimetic, potently inhibits multiple antiapoptotic Bcl-2 family proteins. Ongoing phase 1 studies of ABT-263 show anti-tumor activity in CLL and some lymphomas (Wilson W et al, ASH. 2008). However, thrombocytopenia (TCP) due to on-target Bcl-XL inhibition-induced platelet apoptosis is also observed. Platelet nadir occurred on days 3–5 on 14/21 d dosing with each exposure to drug, was proportional to starting platelet count and recovered during therapy due to compensatory increased megakaryopoiesis. TCP was a dose limiting toxicity (DLT) in 3 patients (pts) in CLL study M06–873 (N = 15) where starting platelet counts tend to be low. We tested 2 stra..

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