Researchers at The University of Texas M. D. Anderson Cancer Center, reporting in the early on-line edition of the March 20 Journal of Clinical Oncology, found that the agent, oblimersen (trade name: Genasense) produced a four-fold increase in "CP/nPR," a clinical response defined by no definitive evidence of disease, in patients who were sensitive to the chemotherapy drug fludarabine, compared to patients who no longer responded to fludarabine.
"The results make sense because oblimersen is designed to work alongside chemotherapy," says the study's lead author, Susan O'Brien, M.D., professor in the Department of Leukemia. "We found in this study that oblimersen enhances sensitivity to chemotherapy, and so we think it deserves further study in a population of CLL patients who are sensitive to chemotherapy agents," she says.
CLL, a cancer of the blood and bone marrow, is the second most common type of leukemia in adults. More than 15,000 new cases of the disease will be diagnosed this year, according to the American Cancer Society, and about 4,500 people will die from the cancer.
Fludarabine is a newer chemotherapy drug that is now being used as first treatment for many patients, according to O'Brien. Oblimersen is an experimental agent that inhibits the production of a protein known as Bcl-2 in cancer cells. This protein can stop a cell from destroying itself, and is often over-expressed in cancer. As an antisense drug, oblimersen provides a complementary genetic strand to the messenger RNA that produces Bcl-2, inactivating it and preventing the protein from being produced. "It gets rid of Bcl-2, and cells that have less Bcl-2 are more sensitive to chemotherapy," O'Brien says.
This study focused on patients who had relapsed after a prior fludarabine - containing regimen or were refractory to fludarabine; refractory patients had failed to respond to a prior fludarabine-based regimen or had progressed within six months of treatment. It enrolled 241 patients at cancer centers worldwide who were randomized to receive fludarabine combined with cyclophosphamide chemotherapy or the same regimen combined with oblimersen.
Researchers found that the primary endpoint of the study (CR/nPR) was achieved in 20 of the 120 patients (17 percent) in the oblimersen-treated group compared to 8 of 121 patients (7 percent) in the group treated with chemotherapy alone. This difference was statistically significant, says O'Brien.
Patients achieving nPR met all the criteria associated with a complete remission, except that on a bone marrow biopsy a nodule could be detected, which might or might not, be cancerous, she says. They did not experience the fever, night sweats, fatigue, abdominal discomfort or other symptoms associated with the disease for at least 180 days.
Although overall response rate was not significantly different between the two groups, maximum benefit was observed in fludarabine-sensitive patients, O'Brien says. This group included 51 patients in the oblimersen group and 50 patients in the group treated with chemotherapy alone, according to researchers.
For example, among all patients, median survival at 36 months was about the same - an estimated 33.8 months in the oblimersen-treated group and 32.9 months in patients treated with chemotherapy. But in patients who achieved CR/nPR, survival was three or more years in 70 percent of the patients in the oblimersen group compared with 38 percent in the chemotherapy-alone group, the researchers found. "Patients who were previously refractory to fludarabine did not benefit substantially from the addition of oblimersen, and because there were so many refractory patients in both arms of the trial, the survival curves were not significantly different between the groups," O'Brien says.
"We aimed to increase the CR/nPR rate to chemotherapy, and that aim was met," O'Brien says. "For CLL patients whose disease has progressed, but who are still sensitive to chemotherapy, oblimersen may represent a new treatment option."
Led by M. D. Anderson, collaborators in the study included investigators in the United States, Canada, Poland, Argentina and Australia.
Julie A. Penne | EurekAlert!
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses