Memantine Delays Cognitive Decline in Brain Tumor Patients Who Receive Whole Brain Radiation Therapy
BOSTON, Oct. 29, 2012 (GLOBE NEWSWIRE) -- Memantine, an N-Methyl-D-aspartate receptor antagonist typically prescribed to Alzheimer's patients, slows cognitive decline in brain cancer patients who receive whole brain radiation therapy (WBRT), according to research presented today at the American Society for Radiation Oncology's (ASTRO's) 54th Annual Meeting.
The phase III trial evaluated the potential protective effects of memantine on cognitive function in 508 patients with brain tumors who received WBRT between March 2008 and July 2010. In addition to cognitive function, the study analyzed the length of time before experiencing cognitive decline, overall survival (OS) and progression-free survival (PFS). Patients received WBRT of 37.5 Gy in 15 fractions and were randomized to receive placebo or a 20mg dose of memantine per day within three days of initiating radiotherapy for 24 weeks. Results demonstrate that memantine delays cognitive decline in areas of recognition memory, global function, executive function and processing speed.
Patients in the memantine group experienced a 17 percent relative reduction in cognitive decline at 24 weeks compared to those in the placebo group. Patients' cognitive function as assessed utilizing the Controlled Oral Word Association test at eight and 16 weeks and the Trail Making Test Part A at 24 weeks also indicated fewer patients in the memantine group experienced decline. Patients were also evaluated at 24 weeks with the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR), which showed a median decline of 0 for patients who received memantine in comparison to those in the placebo group, who had a decline of -2. The trends of all three cognitive tests for the 149 eligible patients who survived 24 weeks indicate that the memantine group yielded better results than the placebo at all points. There was no difference in patients' OS or PFS between the treatment arms.
Patients in the study included adults who exhibited brain metastases and were stratified by recursive partitioning analysis in either Class I or II with or without prior radiosurgery or surgical resection. Patients underwent standardized tests of cognitive function, which were performed at baseline, eight, 16, 24 and 52 weeks. Only 32 percent of patients completed the drug therapy and assessments mainly due to poorer than estimated survival and progressive disease, which led to poor compliance with the treatment protocol. Patients in both groups reported similar levels of Grade 3 and 4 toxicities, including hair loss, fatigue, headache and nausea.
"We are excited to see that adding memantine to the treatment plan for brain tumor patients helps preserve their cognitive function after whole brain radiotherapy even six months after treatment," said Nadia N. Laack, MD, co-author of the study and a radiation oncologist at the Mayo Clinic in Rochester, Minn. "Our findings suggest that memantine may prevent the changes that occur in the brain following radiation therapy, impacting future treatment practices for these patients and suggest a role for further study in other patient populations receiving radiation to the brain."
The abstract, "Memantine for the Prevention of Cognitive Dysfunction in Patients Receiving Whole-brain Radiation Therapy (WBRT): First Report of RTOG 0614, a Placebo-controlled, Double-blind, Randomized Trial," will be presented in detail during the plenary session at ASTRO's 54th Annual Meeting at 2:30 p.m. Eastern time on Monday, October 29, 2012. To speak with Dr. Laack, please call Michelle Kirkwood on October 28 – 31, 2012, in the ASTRO Press Office at the Boston Convention and Exhibition Center at 617-954-3461 or 617-954-3462, or email firstname.lastname@example.org.
ASTRO's 54th Annual Meeting, held in Boston, October 28 – 31, 2012, is the premier scientific meeting in radiation oncology and brings together more than 11,000 attendees including oncologists from all disciplines, medical physicists, dosimetrists, radiation therapists, radiation oncology nurses and nurse practitioners, biologists, physician assistants, practice administrators, industry representatives and other health care professionals from around the world. The theme of the 2012 Annual Meeting is "Advancing Patient Care through Innovation" and examines how innovation in technology and patient care delivery can lead to improved patient outcomes. The four-day scientific meeting includes six plenary papers and 410 oral presentations in 63 oral scientific sessions, and 1,724 posters and 130 digital posters in 18 tracks/topic areas.
ASTRO is the largest radiation oncology society in the world, with more than 10,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy. For more information on radiation therapy, visit www.rtanswers.org. To learn more about ASTRO, visit www.astro.org.
2012 American Society for Radiation Oncology (ASTRO) 54th Annual Meeting
News Briefing, Monday, October 29, 2012, 11:00 a.m. – 11:45 a.m. Eastern time
Scientific Session: Monday, October 29, 2012, 2:30 p.m. – 3:45 p.m. ET, Boston Convention & Exhibition Center
2 Memantine for the Prevention of Cognitive Dysfunction in Patients Receiving Whole-brain Radiation Therapy (WBRT): First Report of RTOG 0614, a Placebo-controlled, Double-blind, Randomized Trial
P. D. Brown1, S. Shook2, N. N. Laack3, J. S. Wefel1, A. Choucair4, J. H. Suh5, D. Roberge6, V. Kavadi7, M. P. Mehta8, D. Watkins-Bruner9, 1University of Texas MD Anderson Cancer Center, Houston, TX, 2RTOG Statistical Center, Philadelphia, PA, 3Mayo Clinic, Rochester, MN, 4Norton Healthcare System Neuroscience Institute, Louisville, KY, 5Cleveland Clinic Foundation, Cleveland, OH, 6McGill University, Montreal, QC, Canada, 7US Oncology, Sugarland, TX, 8Northwestern Memorial Hospital, Chicago, IL, 9Emory University Nell Hodgson Woodfuff School of Nursing, Atlanta, GA
Purpose/Objective(s): Radiotherapy (RT) is an effective therapy for patients with brain tumors. However there are concerns regarding cognitive deterioration after RT. Memantine, an N-Methyl-D-aspartate receptor antagonist, has been shown to be beneficial for vascular and Alzheimer's dementias. Therefore we conducted a phase III trial to evaluate the potential protective cognitive effects of memantine in patients receiving WBRT.
Materials/Methods: Eligible adult patients with brain metastases were stratified by RPA Class (I or II) and prior radiosurgery or surgical resection. Patients received WBRT (37.5Gy in 15 fractions) and were randomized to receive placebo or memantine, 20mg per day, within 3 days of initiating radiotherapy, for 24 weeks. Standardized tests of cognitive function were performed at baseline, 8, 16, 24, and 52 weeks. The primary endpoint, memory decline at 24 weeks defined as the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR), required 442 patients to detect a difference between the treatment arms with 80% power and an alpha of 0.025. Secondary objectives included time to cognitive decline, overall survival (OS), and progression-free survival (PFS).
Results: 554 patients were accrued between March 2008 and July 2010 of whom 508 were eligible. Patient and treatment characteristics were well-balanced between arms. Grade 3 or 4 toxicities and study compliance were similar between arms with only 32% of patients completing drug therapy per protocol mainly due to death, progressive disease or noncompliance. Median follow-up for censored patients was 12.4 months. No differences in OS or PFS were seen between the arms. The memantine arm had significantly longer time to cognitive decline (p=0.02). There was less decline on the HVLT-R DR in the memantine arm (median decline of 0) compared to the placebo arm (median decline of -2) at 24 weeks (p=0.059) that was not statistically significant as 148 analyzable patients at 24 weeks resulted in only 35% statistical power. There was less decline on the HVLT-R Delayed Recognition in the memantine arm at 24 weeks (p=0.015). Fewer patients receiving memantine experienced decline on the Controlled Oral Word Association test at 8 (p=0.008) and 16 weeks (p=0.004) or the Trail Making Test Part A at 24 weeks (p=0.014).
Conclusions: Even though no statistically significant difference was seen in delayed recall, patients treated with memantine had better cognitive function over time; specifically memantine delays time to cognitive decline and reduces the rate of decline in recognition memory, executive function and processing speed in patients receiving WBRT.
Supported by grants RTOG U10 CA21661 and CCOP U10 CA37422 from the NCI and by Forest Pharmaceuticals.
Author Disclosure Block:
P.D. Brown: None. S. Shook: None. N.N. Laack: None. J.S. Wefel: None. A. Choucair: None. J.H. Suh: None. D. Roberge: None. V. Kavadi: None. M.P. Mehta: F. Honoraria; Speaker: ASCO,Cleveland Clinic, GRACE Foundation, IL Radiological Society, Institute for Medical Education, MDACCC, Merck, priME Oncology, Resurrection Hospital, Strategic Edge, UT San Antonio, Vindico,WebMD. G. Consultant; Abbott, BioStrategies, Bristol-Meyers-Squibb (Knowledgepoint), Elekta, Frankel Group, Gerson, MAPI Values, Merck, NCI, Novartis (Articulate Science), Novellos, Quark, SS Bala, Tomotherapy, US Oncology, Vertex. J. Funding Other; Medical Advisory Boards: Colby, Stemina, Procertus; Protocol Data Review: Adnexus; Data Safety Monitoring Boards: Apogenix;. L. Stock Options; Accuray,Colby, Pharmacyclics, Procertus, Stemina. O. Patent/License Fee/Copyright; WARF; Royalties: DEMOS; Publishers: Elsevier; CME Products: MCM, Medscape. Q. Leadership; Board of Directors: Pharmacyclics. D. Watkins-Bruner: None.