Velcade™ Plus Chemotherapy Promising in Refractory Multiple Myeloma

Velcade™ Plus Chemotherapy Promising in Refractory Multiple Myeloma

According to results presented at the 39th annual meeting of the American Society of Clinical Oncology, the addition of Velcade (bortezomib) to Adriamycin® produces impressive anti-cancer responses in patients with multiple myeloma who have stopped responding to previous therapies.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone. Furthermore, the cancerous plasma cells secrete dysfunctional antibodies, referred to as M proteins, which can be measured in the blood. Once multiple myeloma stops responding to standard therapies, it is referred to as refractory. Patients with refractory multiple myeloma are currently left with few effective treatment options and long-term survival is suboptimal.

Proteosomes are proteins existent in virtually every cell that are responsible for the breakdown and re-use of other proteins in a cell. Through regulating several aspects of cellular activity, proteosomes are greatly responsible for activation of survival pathways of a cell. Velcade, a proteosome inhibitor, has demonstrated an inhibitory effect on cellular survival through its activity on proteosomes. In addition, Velcade has demonstrated the ability to re-sensitize cancer cells to the killing effects of chemotherapy in refractory myeloma cells. Velcade was recently approved by the FDA as a single agent for the treatment of relapsed or refractory multiple myeloma.

Researchers from the University of North Carolina recently conducted a clinical trial to evaluate the combination of Velcade with Adriamycin®, a commonly used chemotherapy agent. This trial involved 20 patients with refractory multiple myeloma, including patients who had stopped responding to prior therapy with Adriamycin®. Following treatment with Velcade and Adriamycin®, 12 patients achieved a complete disappearance of detectable cancer (complete response), 7 patients achieved a partial disappearance of cancer (partial response) and 7 patients achieved a minor anti-cancer response or disease stabilization. Only one patient experienced a progression of cancer following therapy. Treatment was generally well tolerated.

The researchers concluded that Velcade plus Adriamycin® produces an impressive proportion of anti-cancer responses in patients with refractory multiple myeloma, including those who were previously resistant to Adriamycin®. Longer follow-up is necessary to determine if the anti-cancer responses will result in improved survival. Future clinical trials directly comparing Velcade to Velcade plus Adriamycin® or other common chemotherapy agents are warranted to determine the true clinical benefit of combination therapy. Patients with refractory multiple myeloma may wish to speak with their physician regarding the risks and benefits of Velcade plus chemotherapy or the participation in a clinical trial evaluating other novel therapeutic approaches.

Reference: Orlowski R, Voorhees P, Garcia R, et al. Phase I study of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with refractory hematological malignancies. Proceedings from the 39th annual meeting of the American Society of Clinical Oncology. 2003. Abstract #801.

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