Clinical trials of R-(-)-gossypol (AT-101) in newly diagnosed and recurrent glioblastoma: NABTT 0602 and NABTT 0702.

ABSTRACT:

Purpose

AT-101 is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of the parent compound, racemic gossypol, demonstrated objective and durable responses in patients with malignant glioma. AT-101 has demonstrated synergy with radiation in animal models. The objectives of trial NABTT 0602 were to determine the MTD of AT-101 concurrent with temozolomide (TMZ) and radiation therapy (RT) (Arm I) and to determine the MTD of AT-101 when given with adjuvant TMZ after completion of standard chemoradiation (Arm 2). Separately in trial NABTT 0702, the survival and response rates of single agent AT-101 were evaluated in patients with recurrent glioblastoma.

Methods

In NABTT 0602 Phase I, a 3+3 design was use

SUBMITTER: Fiveash JB 

PROVIDER: S-EPMC10824421 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature