Genasense®/Thalomid®/Dexamethasone Promising for Recurrent Multiple Myeloma

According to an article recently published in the Journal of Clinical Oncology, the treatment combination of Genasense® (oblimersen), Thalomid® (thalidomide) and dexamethasone appears promising in the treatment of recurrent multiple myeloma.

One obstacle to treating recurrent or refractory cancers is that cancer cells often become resistant to the cancer-killing effects of various forms of therapy. One mechanism currently being investigated through which this resistance occurs is Bcl-2 expression. Bcl-2 is a protein that exists in delicate balance with other related proteins. One of its known functions is to prevent cells from apoptosis (death). Through several mechanisms not entirely understood, Bcl-2 proteins protect cancer cells from the lethal effects of therapy. Various types of cancers have higher than normal levels of Bcl2 proteins—this often results in a poorer prognosis than cancers without high levels of Bcl-2.

Genasense is a new agent still being evaluated in clinical trial that utilizes a relatively novel approach to treat cancer: Genasense inhibits or reduces the production of Bcl-2 protein by binding to the specific molecules that are involved in the process of producing Bcl-2 proteins. This binding action stops or reduces production of Bcl-2 proteins within a cell, making the cell sensitive to anti-cancer therapy agents. Previous studies demonstrate that Genasense amplifies the cytotoxicity (ability to kill cancer cells) of many therapeutic agents for a variety of different blood cancers. Studies have also demonstrated that Genasense has anti-cancer activity in various cancers when used as a single agent.

Researchers from the University of Maryland and the National Cancer Institute (NCI) recently conducted a clinical trial evaluating the treatment combination of Genasense, Thalomid and the steroid dexamethasone.

This trial included 33 patients with multiple myeloma—31 who had cancer progression following an autologous stem cell transplant and 15 who had cancer progression following treatment with Thalomid. Following treatment with Genasense/Thalomid/dexamethasone, overall anti-cancer responses were achieved in over half of patients (55 percent).

Reference: Badros AZ, Goloubeva O, Rapoport AP, et al. Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients. Journal of Clinical Oncology. 2005;23:4089-4099.