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.
Tolcher
A W
AW
Institute for Drug Development, Cancer Therapy and Research Center, and the University of Texas Health Science Center, San Antonio, TX, USA.
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D019254:Genes, bcl-2; D006801:Humans; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids; D013873:Thionucleotides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D043823:Taxoids; D013873:Thionucleotides; D000077143:Docetaxel; C408162:oblimersen; D017239:Paclitaxel