Methylphenidate Helps Childhood Cancer Survivors

Roxanne Nelson

September 23, 2010

September 23, 2010 — Children treated for malignant brain tumors or acute lymphoblastic leukemia (ALL) are at significant risk for cognitive impairment. Now, for the first time, a year-long study has shown that treatment with methylphenidate (MPH), a stimulant used to treat attention deficit hyperactivity disorder (ADHD), can improve attention and behavioral problems in childhood cancer survivors.

The findings were published online September 13 in the Journal of Clinical Oncology.

The authors found that, compared with control subjects, children treated with MPH showed significant improvement in their performance on the Conners' Continuous Performance Test (CPT), a computerized measure of sustained attention. There was also significant improvement in parent, teacher, and self-reported ratings of attention. For some children, scores on the attention and behavior measures returned to normal ranges.

Because of the study design and the strength of the data, lead author Heather Conklin, PhD, believes that this is a treatment option that can be discussed with families. "But this is just one component of any treatment regimen," she emphasized.

For children who have demonstrated attention problems, MPH can be an integral component of a treatment plan that includes nonpharmacologic options, explained Dr. Conklin, a pediatric neuropsychologist at St. Jude Children's Research Hospital in Memphis, Tennessee. "In some children, the attention problems preclude focusing on behavioral interventions, so MPH can be a starting point."

This is a very impressive study.

This is a very impressive study; it is innovative and well thought out and balanced, said Bartlett D. Moore, PhD, professor and chief, Section of Behavioral Pediatrics at the University of Texas M.D. Anderson Cancer Center in Houston.

"This study is important because more and more children are surviving cancer only to be challenged by learning and cognitive deficits," said Dr. Moore, who was approached by Medscape Medical News for independent comment. "Survivors with attention deficits can show long-term improvement, which may eventually manifest as better school performance."

He noted that future studies should use a similar design and compare the effectiveness of different stimulant medications for ADHD. "Children with ADHD typically show greater benefit when behavioral strategies are used alongside medication to maximize their attention and concentration skills," said Dr. Moore. "Therefore, a trial incorporating a well thought out behavioral modification plan and medication would be beneficial."

First Study to Date

This is the first study to demonstrate that some survivors of pediatric cancers can benefit from the long-term use of MPH. Participants were followed for 1 year; therefore, the optimal length of time that MPH is needed to retain benefit is not known in this population, Dr. Conklin said in an interview. "We know from the ADHD literature that there is a group that outgrows the need for the medication, while other children can learn compensatory strategies."

This study represents a big advance, she pointed out, in terms of factors such as sample size, length of follow-up period, and use of objective assessment tools. "And the children who have shown improvement have remained on the therapy," she said.

The study is the final phase of a multiphase trial that evaluated the potential benefits of MPH for survivors of childhood cancer who are experiencing attention and learning difficulties. Patients who tolerated the medication after a 2-day, in-clinic, double-blind, crossover trial went on to participate in a 3-week trial that consisted of placebo, low-dose MPH (0.3 mg/kg; maximum dose, 10 mg twice daily), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg twice daily).

The patients selected for the 12-month trial had shown improvement on specific assessment tools after treatment with MPH.

Improvements in Behavior, None in Academics

A total of 68 children (35 who survived brain tumors, 33 who survived ALL) completed the study, along with 54 cancer survivors who served as a control group. Attention was measured with the CPT and Conners' Rating Scales (CRS); academic abilities with the Wechsler Individual Achievement Test; social skills with the Social Skills Rating System (SSRS); and behavioral problems with the Child Behavior Checklist (CBCL).

The dose of MPH was determined by a multidisciplinary team, and was individually titrated. For both the MPH and control groups, assessments were made at baseline and at the end of the trial using the standardized tools.

The MPH group showed a significant improvement in performance on a measure of sustained attention (CPT indices; P < .05); parent, teacher, and self-report ratings of attention (CRS indices; P < .05), and parent ratings of social skills or behavioral problems (SSRS and CBCL indices; P < .05).

Conversely, only parental ratings of attention and social skills improved during the same period for the control group. There was no statistical difference between pre- and posttesting on performance measures of attention.

Neither group showed any change in intellectual functioning or academic skills. However, the authors note that even though they were unable to identify any improvement in academic measures, a number of parents reported that children who received MPH experienced an improvement in school grades related to behavior changes. These included studying in advance for exams, remembering to turn in assignments, and advance planning for projects.

The study was funded in part by the National Cancer Institute and by the American Lebanese Syrian Associated Charities. Coauthor Ronald Brown, PhD, from Temple University, Philadelphia, Pennsylvania, reports consulting/advising for and receiving honoraria from Shire Pharmaceuticals. None of the other authors have disclosed any relevant financial relationships.

J Clin Oncol. Published online September 13, 2010. Abstract

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