Preliminary phase I results of G3139 (bcl-2 antisense oligonucleotide) therapy in combination with docetaxel in hormone-refractory prostate cancer.

The transition from androgen-dependent to androgen-independent prostate cancer is accompanied by a number of molecular genetic changes, including overexpression of the bcl-2 gene. Overexpression of Bcl-2 protein decreases the pro-apoptotic response to such cellular insults as irradiation, chemotherapy, and androgen withdrawal. Reduction of Bcl-2 expression in hormone-refractory prostate cancer (HRPC) preclinical models markedly increases the antitumor efficacy of docetaxel both in vitro and in vivo. Thus, a phase I/II pharmacokinetic and biologic correlative study has been initiated in patients with HRPC to examine whether docetaxel therapy can be enhanced with a therapeutic antisense oligodeoxynucleotide (G3139) directed at bcl-2 gene expression. Semin Oncol 28 (suppl 15):67-70. Copyright 2001 by W.B. Saunders Company.