Nav: Home

Leukemia drug combo is encouraging in early Phase I clinical trial

December 05, 2016

SAN DIEGO, CA (December 5, 2016)--Researchers from Columbia University Medical Center and NewYork-Presbyterian reported that 8 out of 12 patients with relapsed and/or chemotherapy refractory acute myeloid leukemia (AML) or other blood cancers responded to a regimen including the chemotherapy drugs thioguanine and decitabine. Results from this small phase I study were reported at the American Society of Hematology's annual conference.

"Outcomes are typically poor for older patients with advanced blood cancers, and new therapies are desperately needed to help patients with these cancers achieve remission," said Mark Frattini, MD, PhD, associate professor of medicine at Columbia University Medical Center (CUMC) and blood cancer specialist at NewYork-Presbyterian. "While our study was small, the response we saw in this phase I, dose-escalating trial was encouraging."

Previously, Frattini and colleagues had used a proprietary chemosensitivity screening assay to demonstrate that combining thioguanine and decitabine--chemotherapy drugs that are commonly used as single agents to treat patients with AML--restored therapeutic efficacy in leukemia cells from patients with relapsed and/or refractory disease.

In this study, the researchers tested the efficacy of the combination therapy in 12 older patients (median age of 67 years) with relapsed or chemotherapy refractory AML or chronic myelomonocytic leukemia, including 6 patients whose disease progressed after being treated previously with decitabine as a single agent. Of these, 11 patients completed the first treatment cycle, and 6 completed a second cycle, with a median of 3 rounds of treatment. Eight of the 11 evaluable patients responded to the combination therapy, including 6 who achieved a complete remission (5 in complete remission with incomplete count recovery). In addition, all of the patients who had progressed after prior treatment with decitabine alone responded to the combination therapy, demonstrating that the combination could overcome disease resistance to decitabine. Chemosensitivity assay results, obtained before treatment, accurately predicted each patient's response to the combination therapy.

After treatment with the combination therapy, 4 of the responders went on to have a stem cell transplant.

"The goal of chemotherapy for patients with relapsed and/or refractory AML and other blood cancers is to achieve a remission that enables them to undergo a potentially curative stem cell transplant," said Dr. Frattini. "With our phase I results, we have shown that this combination therapy can get some patients--including those who failed to respond to or progressed after previous chemotherapy treatment with a single agent such as decitabine--to that point. The next challenge for hematologic oncologists is to reduce morbidity and mortality associated with stem cell transplantation."

After the study, 2 of the patients who had a stem cell transplant died from transplant-related toxicity, and another relapsed. One patient has remained in remission for more than 2 years.
-end-
The study is titled, "Final Results of a Phase I Trial of a Pharmacodynamically Conceived Thioguanine/Decitabine Combination in Patients with Advanced Myeloid Malignancies." The other contributors are: Daniel J. Lee (Columbia University Medical Center, New York, NY), Todd L. Rosenblat (CUMC), Mark Lawrence Heaney (CUMC), Joseph G. Jurcic (CUMC), Azra Raza (CUMC), Kristina Gazivoda (CUMC), Katherine Harwood (CUMC), Ryan Shelton (CUMC), Hakim Djaballah (Institut Pasteur Korea, Seoul, Republic of Korea), Joseph M. Scandura (Weill Cornell/NewYork-Presbyterian, New York, NY), and Anthony Letai (Dana-Farber Cancer Institute, Boston, MA).

The study was supported by an award from the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center.

Dr. Jurcic's research is funded by Astellas. Dr. Letai receives funding from and is a consultant for from Astra-Zeneca, Tetralogic, and AbbVie. The researchers declare no additional conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.

NewYork-Presbyterian

NewYork-Presbyterian is one of the nation's most comprehensive healthcare delivery networks, focused on providing innovative and compassionate care to patients in the New York metropolitan area and throughout the globe. In collaboration with two renowned medical school partners, Weill Cornell Medicine and Columbia University College of Physicians & Surgeons, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and clinical innovation.

NewYork-Presbyterian has four major divisions: NewYork-Presbyterian Hospital is ranked #1 in the New York metropolitan area by U.S. News and World Report and repeatedly named to the magazine's Honor Roll of best hospitals in the nation; NewYork-Presbyterian Regional Hospital Network is comprised of leading hospitals in and around New York and delivers high-quality care to patients throughout the region; NewYork-Presbyterian Physician Services connects medical experts with patients in their communities; and NewYork-Presbyterian Community and Population Health features the hospital's ambulatory care network sites and operations, community care initiatives and healthcare quality programs, including NewYork Quality Care, established by NewYork-Presbyterian, Weill Cornell and Columbia.

NewYork-Presbyterian is one of the largest healthcare providers in the U.S. Each year, nearly 29,000 NewYork-Presbyterian professionals deliver exceptional care to more than 2 million patients.

For more information, visit http://www.nyp.org and find us on Facebook, Twitter and YouTube.

Columbia University Medical Center

Related Chemotherapy Articles:

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.
Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.
Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.
A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.
Chemotherapy or not?
Case Western Reserve University researchers and partners, including a collaborator at Cleveland Clinic, are pushing the boundaries of how 'smart' diagnostic-imaging machines identify cancers -- and uncovering clues outside the tumor to tell whether a patient will respond well to chemotherapy.
More Chemotherapy News and Chemotherapy Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...