Research shows bortezomib benefits a third of multiple myeloma patients

June 25, 2003

CHAPEL HILL -- Bortezomib, a new cancer-fighting drug also called Velcade, shows promise for treating patients whose multiple myeloma no longer responds to conventional chemotherapy, a new clinical study concludes.

About 35 percent of 193 relapsed patients treated in the multi-center phase 2 clinical trial responded positively to the compound, researchers found, including seven whose myeloma protein became undetectable and 12 whose telltale protein could be found only with a special test called immunofixation. Overall, side effects were manageable.

A report on the encouraging findings appears in the June 26 issue of the New England Journal of Medicine.

Authors include Drs. Paul G. Richardson, instructor in medicine at Harvard University Medical School, Kenneth C. Anderson, professor of medicine at Harvard and director of the Dana-Farber Cancer Institute's multiple myeloma center, and Robert Z. Orlowski, assistant professor of medicine at the University of North Carolina at Chapel Hill School of Medicine.

Dr. Beverly S. Mitchell, professor and chief of hematology/oncology at UNC, wrote a separate accompanying commentary. Mitchell and Orlowski are members of UNC's Lineberger Comprehensive Cancer Center.

Multiple myeloma, a cancer of plasma cells, is the second most common cancer arising from blood-related tissue, Orlowski said. The American Cancer Society estimates that 13,600 new U.S. residents will be diagnosed this year with the disease, the 10th leading cause of cancer death in women and a cancer seen more commonly among blacks.

"Patients typically experience fatigue, bony pain and anemia and sometimes suffer bone and kidney damage as well," he said. "While therapies are available for multiple myeloma, most patients cannot be cured of the disease. Furthermore, myeloma tends to become resistant to treatment and less and less responsive to the few available chemotherapies, with briefer periods of remission. New drugs are badly needed so that patients will have additional treatment options."

Bortezomib, formerly known as PS-341, has shown special promise in the treatment of myeloma, Orlowski said.

"This drug inhibits an important protease, or enzyme, that is present in all cells but is especially interesting because studies performed in part in our laboratory showed that cancer cells are much more sensitive to its effects than are normal cells," he said. "A phase 1 clinical study we performed, along with investigators at Memorial Sloan Kettering, showed that the drug could be given safely."

Several myeloma patients benefitted significantly from the treatment, including one whose disease went into remission.

"As a result of those findings and also encouraging laboratory studies by

Dr. Anderson at Dana-Farber, a group of investigators led by Drs. Richardson and Anderson performed a larger clinical study," Orlowski said. "In the new research, patients were treated with bortezomib, and the results confirmed significant clinical benefits from therapy, including some patients who had complete responses."

The results led to recent Food and Drug Administration approval. A phase 3 clinical trial is now under way comparing bortezomib's efficacy with a standard myeloma treatment.

"Studies are also looking at using it in patients with myeloma who have not received other therapy before since these patients may have disease that is more sensitive to this drug," Orlowski said "Combination studies with other chemotherapies are examining whether there might be even better activity if bortezomib is added to other drugs for myeloma. The drug already offers a new, active option for patients with advanced myeloma, and the studies we're doing will help to determine its best role."

UNC's Mitchell wrote that now is an exciting time for anti-cancer drug treatment.

"The identification of promising molecular targets has led to the development of many exciting new drugs for which an anti-tumor mechanism of action has been clearly delineated," she wrote. "Given the recent major advances in our understanding of the biology of cancer cells, one might surmise that an era of truly rational therapeutics has arrived. Nevertheless, we continue to find new therapeutic agents that target unforeseen molecular pathways."

The new report "brings to the fore a relatively new and unexpected target," a large protein complex called the 26S proteasome, which is found in high amounts in both the cytoplasm and nucleus of all eukaryotic cells, Mitchell said. Among the complex's several key jobs is to break down selected proteins as a central part of cell metabolism.

"At first glance, the features of the proteasome would scarcely make it a plausible target for highly selective cancer therapy," she wrote. Nonetheless, it "would appear that the sensitization of tumor cells to cytotoxic drugs through inhibition of the proteasome will continue to generate enthusiasm for numerous clinical applications."
By David Williamson
UNC News Services

Millennium Pharmaceuticals of Cambridge, Mass., supported the research. Medical scientists from 12 other U.S. cancer centers, including those at Northwestern University, the Mayo Clinic and Massachusetts General Hospital, and Millennium Pharmaceuticals also participated in the study.

Note: Orlowski and Mitchell can be reached at 919-966-9762 and 966-5720, respectively, and
Richardson and Anderson at 617-632-2127.
Lineberger Cancer Center Contact: Dianne Shaw, 919-966-5905
News Services Contact: David Williamson, 919-962-8596

University of North Carolina at Chapel Hill

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to