ATRA and arsenic trioxide versus ATRA and idarubicin for newly diagnosed, non high-risk acute promyelocytic
New research demonstrates the efficacy of the first curative treatment for acute promyelocytic leukemia (APL) that does not include chemotherapy, marking an important step toward front-line use of targeted therapies for acute leukemia.
APL is an uncommon, yet aggressive, subtype of acute myeloid leukemia (AML) in which there are too many immature white blood cells in the bone marrow, leading to a shortage of normal white and red blood cells and platelets in the blood, which is associated with clotting defects that can cause serious bleeding. Without prompt diagnosis and treatment, APL can be fatal in a matter of hours or days.
Early treatment regimens for APL relied heavily on anthracycline-based chemotherapy with daunorubicin or idarubicin. In the early 1990s, research supported the addition of a non-chemotherapeutic agent, all-trans-retinoic acid (ATRA, a vitamin A derivative developed from ancient Chinese herbal medicine), to standard regimens. ATRA causes cancer cells to develop fully into mature blood cells, which progress through full differentiation and eventually die (unlike leukemia cells that are unable to fully mature). The combination regimen of chemotherapy and ATRA dramatically improved the survival outlook for those with APL and made the disease curable in up to 80 percent of patients. More recently, another natural compound, arsenic trioxide (ATO), was integrated into APL treatment, showing higher efficacy and better tolerability when compared with conventional chemotherapy. Today, as investigators continue to report the success of targeted cancer therapies (best exemplified by imatinib for chronic myeloid leukemia), researchers have questioned whether traditional toxic chemotherapy is still necessary to achieve high cure rates for patients with APL.
To investigate whether a combination of ATO+ATRA could provide the same therapeutic benefit as conventional treatment including chemotherapy, researchers from the Italian-German cooperative teams Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), Study Alliance Leukemia (SAL) group, and German-Austrian AML Study Group (AMSLG) designed a multicenter, international Phase III trial in which 162 patients with standard-risk APL were divided into two treatment arms. Patients in Arm A received a regimen of ATO+ATRA, while patients in Arm B received the standard ATRA+idarubicin (AIDA) treatment regimen. The primary study objective was event-free survival (EFS) at two years, with secondary objectives including overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) rates, molecular response, and safety.
Results suggest that the targeted ATO+ATRA therapy strategy might offer similar efficacy to the chemotherapy-based regimen. In the 154 patients who were evaluable for response, complete remission was achieved in all patients (100%) in the ATO+ATRA arm and 95 percent in the AIDA arm. EFS was observed in 97 percent in the ATO+ATRA arm, with one death and two relapses, compared to 86.7 percent in the AIDA arm, in which seven deaths and four relapses were observed. Overall survival, DFS, and CIR rates were 98.7 percent, 97 percent, and 1.6 percent, respectively, in the ATO+ATRA arm, versus 91.1 percent, 91.6 percent, and 4.3 percent, respectively, in the AIDA arm. Additionally, fewer side effects (fever, low neutrophil and platelet counts) were observed in the ATO+ATRA arm.
"This is one of the first times that we can report the success of a treatment strategy for an acute leukemia that relies solely on targeted molecular therapy," said Francesco Lo-Coco, MD, lead author and Chairman of the APL subcommittee of the Italian GIMEMA group and Professor of Hematology at University Tor Vergata in Rome, Italy. "Our results are an important step toward the further utilization of targeted therapies for other types of leukemia, as we begin to focus on improving the overall treatment experience for patients by offering new strategies that deliver the same efficacy as traditional options with considerably lower toxicity."
Provided by American Society of Hematology
- Arsenic early in treatment improves survival for leukemia patients Nov 11, 2010 | not rated yet | 0
- Scientists find genetic key to why some cancer patients don't respond to treatment Jan 05, 2012 | not rated yet | 0
- Tranylcypromine antidepressant shows promise as cancer treatment Mar 11, 2012 | not rated yet | 0
- Better prognosis for early blast clearance in leukemia Oct 24, 2012 | not rated yet | 0
- Adding bavituximab to second-line chemotherapy doubles response rate Sep 06, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer 20 hours ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 21 hours ago | not rated yet | 1
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
Cancer May 18, 2013 | 5 / 5 (2) | 0
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer May 17, 2013 | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer May 17, 2013 | not rated yet | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
8 hours ago | not rated yet | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
9 hours ago | 5 / 5 (2) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
9 hours ago | 4.8 / 5 (4) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
8 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
13 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
8 hours ago | not rated yet | 0