Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Arsenic early in treatment improves survival for leukemia patients

12.11.2010
Arsenic, a toxic compound with a reputation as a good tool for committing homicide, has a significant positive effect on the survival of patients with acute promyelocytic leukemia (APL), when administered after standard initial treatment, according to a new, multi-center study led by a researcher at Wake Forest University Baptist Medical Center.

While arsenic trioxide (As2O3) is known by clinicians to be a highly effective treatment for patients with relapsed APL, its benefit earlier in treatment, after first remission, has remained unknown…until now.

Researchers with the Cancer and Leukemia Group B, a group of cancer and leukemia researchers funded by the National Cancer Institute, led a study to determine if, by administering arsenic trioxide earlier – after a patient has finished standard initial treatment and reached first remission – they could improve survival rates. The results were dramatic.

"Patients with APL can achieve remission with standard treatment (chemotherapy plus ATRA, an oral vitamin A-based compound), but it often comes back," said Bayard L. Powell, M.D., a professor of hematology and oncology at Wake Forest Baptist, principal investigator and lead author on the study. "Arsenic trioxide is then used to get them back into remission, often followed by a bone marrow transplant to try to cure the patient. For this study, we used arsenic as an early "consolidation therapy" after the initial standard treatment to essentially, as one of our first patients described, 'seal the deal' the first time around. Not only did the leukemia rarely return in the patients who received the arsenic, those patients also lived longer."

The findings appear in the November 11 issue of Blood.

APL accounts for about 10 to 15 percent of acute myeloid leukemia cases and presents most frequently in young adults. It is associated with a very high risk of severe bleeding complications, including early death from bleeding into the brain.

Current treatment of APL involves a combination of all-trans retinoic acid (ATRA) plus chemotherapy to induce remission, followed by additional "consolidation" chemotherapy to strengthen the remission, followed by further ATRA with or without oral chemotherapy to maintain remission. This approach yields complete remission rates of about 90 percent and improved event-free survival, with an "event" defined as failure to achieve complete remission, relapse after achieving complete remission, or death.

Those with high white blood cell counts at diagnosis have a worse prognosis, however, with higher risk of early death during initial standard treatment. If they survive initial treatment and enter remission, they are also more prone to relapse, at which point arsenic is introduced to push them back into remission.

While arsenic can be toxic and is used in potent pesticides and poisons, it also exists naturally in the environment and, when manufactured under carefully-controlled conditions and used appropriately by doctors and nurses experienced in the treatment of cancer, can provide a significant health benefit.

Arsenic has been proven effective in pushing those unresponsive to initial treatment, and those who relapse after initial response, into remission. But researchers wanted to know what would happen if they used the arsenic trioxide after initial standard treatment, rather than wait until a patient relapses.

For the study, North American Leukemia Intergroup trial C9710, investigators randomized 481 patients with untreated APL, age 15 and older, into two groups. Both groups would receive standard treatment of ATRA plus chemotherapy, followed by standard consolidation therapy. One of the groups received an additional two 25-day courses of intravenous arsenic trioxide before administration of the standard consolidation therapy.

The patients in the investigational group received arsenic trioxide intravenously for one hour, five days a week, for five weeks, with a two-week break between courses.

After initial standard treatment, both groups experienced similar rates of remission, at about 90 percent, and there were no treatment-related deaths reported from either group during consolidation therapy, indicating that the addition of arsenic treatment earlier introduces no additional safety concerns.

Analysis of the overall results revealed that event-free survival, defined as the time from study entry to first event (defined above), was significantly better for patients randomized to receive the arsenic trioxide consolidation therapy, For example, after three years, event-free survival was 80 percent in the arsenic group versus 63 percent in the non-arsenic group. Arsenic trioxide consolidation provided significant benefit to patients in the investigational group regardless of their initial prognosis based on white blood cell count and other risk factors.

The group who received arsenic also faired better in relapse rates and overall survival, researchers found. Out of 196 study participants who received at least one dose of arsenic after initial standard treatment, only seven individuals – four percent – relapsed within three years of follow-up.

"We think people who received the arsenic trioxide after initial standard treatment are likely cured," Powell said. "There have been no relapses in that group after 36 months. The use of arsenic earlier in treatment improves the cure rate and survival, and it does so with little or no additional toxicity."

The results are exciting, Powell said. "It gives us hope that, with the addition of arsenic trioxide earlier in treatment, we may be able to eliminate some of the chemotherapy and reduce toxicities and costs."

However, 19 patients (eight percent) in each group died during the initial standard treatment, Powell pointed out, and those who were randomized to receive the arsenic never got a chance to benefit from it, since they didn't live through the initial treatment.

"One of our next objectives is to reduce or eliminate these early deaths – most common in patients with high white blood cell counts – possibly by introducing arsenic even earlier than we did this time, as part of initial induction therapy, to help them achieve remission," Powell said. "Some of these patients are at such high risk that they may need the arsenic just to get them into remission, so they have a chance."

Powell's co-authors in the North American Leukemia Intergroup study are Barry Moser, Ph.D., Wendy Stock, M.D., Richard M. Stone, M.D., and Richard A Larson, M.D., of Cancer and Leukemia Group B (CALGB), in Chicago, IL; Robert E. Gallagher, M.D., Jacob M. Rowe, M.D., and Martin S. Tallman, M.D., of the Eastern Cooperative Oncology Group (ECOG), in Brookline, MA; Cheryl L. Willman, M.D., Steven Coutre, M.D., and Frederick R. Appelbaum, M.D., of Southwest Oncology Group (SWOG), in San Antonio, TX; James H. Feusner, M.D., and John Gregory, M.D., of Children's Oncology Group (COG), in Arcadia, CA; and Stephen Couban, M.D., of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG), in Kingston, ON, Canada.

Media Contacts: Bonnie Davis, bdavis@wfubmc.edu, (336) 716-4977; Marguerite Beck, marbeck@wfubmc.edu, (336) 716-2415; or Main Number (336) 716-4587.

Wake Forest University Baptist Medical Center (www.wfubmc.edu) is an academic health system comprised of Wake Forest University Health Sciences, which operates the university's School of Medicine, Wake Forest University Physicians and North Carolina Baptist Hospital. U.S. News & World Report ranks the School of Medicine among the nation's best medical and osteopathic schools: 33rd in primary care, 44th in research, 23rd for its physician assistant program, and 11th for its joint program with the UNC-Greensboro to train nurse anesthetists. Best Doctors in America includes 214 of the Wake Forest medical school faculty. The institution is in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property. The Medical Center has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993.

Bonnie Davis | EurekAlert!
Further information:
http://www.wfubmc.edu

More articles from Health and Medicine:

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>