SAN DIEGOIn preclinical studies, Ligand Pharmaceuticals
Targretin (LGD1069, also known as bexarotene) plus tamoxifen
(Nolvadex) produced a response rate of 94% in tamoxifen-resistant
breast tumors, compared with 33% for long-term tamoxifen therapy
alone, said Ligand scientist Eric Bischoff.
Targretin is a synthetic retinoid analogue that selectively activates
a subclass of retinoid receptorsretinoid X receptorsthat
play an important role in the control of cellular function. This new
class of agents, known as rexinoids, offers a novel approach to the
treatment of breast tumors that escape sensitivity to antihormonal
therapies, such as tamoxifen, Mr. Bischoff said at the 90th annual
meeting of the American Association for Cancer Research
Mr. Bischoff and his colleagues William W. Lamph, PhD, and Richard A.
Heyman, PhD, designed a novel tamoxifen-resistant animal model of
breast cancer for use in the study.
Ligand has launched an open-label phase II clinical trial of
Targretin in advanced breast cancer patients, with interim results
expected this year. The trial is assessing the efficacy, safety, and
tolerability of two dose levels of Targretin capsules (200 and 500
mg/m²/d) in up to 180 women with metastatic breast cancer. The
study is being conducted at approximately 30 centers throughout the
Researchers plan to include up to 60 patients in each of three groups
based on prior therapy: patients for whom standard chemotherapy is no
longer effective, patients for whom standard hormonal therapy is no
longer effective, and patients currently being treated with tamoxifen
whose disease has progressed.
Patients in the tamoxifen-treated group will remain on tamoxifen, and
Targretin will be added to their therapy regimen. Each patients
tumor status will be evaluated every 8 weeks for the first 6 months
of the study and every 12 weeks thereafter, the company said.