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

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.

Multiple myeloma is a cancer of the blood that affects the plasma cells. Plasma cells, which produce antibodies to help fight infection and disease, are a vital part of the immune system. In multiple myeloma an excess of abnormal plasma cells is produced. This results in symptoms such as increased risk for bacterial infections or impaired immune responses. Other effects of myeloma may include damage to the kidneys, osteoporosis, anemia and an elevated blood calcium level.

Although multiple myeloma is not curable, it can be treated to allow patients to live longer, healthier lives. Treatment options for multiple myeloma include watchful waiting, chemotherapy, radiation, steroids, Thalomid, Velcade® (bortezomib) and, in some cases, stem cell transplantation.

Recurrent multiple myeloma refers to cancer that has recurred or progressed following previous therapies. Researchers continue to evaluate treatment that will improve the duration of survival for patients with recurrent multiple myeloma, while keeping side effects to a minimum.

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. Thalomid is an anti-angiogenic agent that reduces or prevents the growth of blood vessels to cancer cells. This action cuts off the cells’ nutrient and oxygen supply. Thalomid is also thought to have several other biologic properties that provide anti-cancer activity.

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). Of the 15 patients who had received prior Thalomid, seven achieved an anti-cancer response following the treatment regimen utilized in this trial. The response lasted approximately 13 months on average, and overall survival was 17 months.

The researchers concluded that the treatment combination of Genasense, Thalomid and dexamethasone appears to have promising activity in recurrent multiple myeloma. The authors suggested that clinical trials further evaluating Genasense in combination with different therapies is warranted. Patients with recurrent multiple myeloma may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating Genasense or other promising therapeutic approaches.

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.

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