Methadone is a pain-relief option for children with advanced cancer and chronic pain, according to a study presented here at the 2017 ASCO Palliative Care in Oncology Symposium.
“Methadone as the first long-acting opioid in children with advanced cancer is both effective and safe,” said Kevin Madden, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, on October 27.
The retrospective chart review involved 52 consecutive patients (median age, 12.5 years; median weight, 42 kg; 58% male) treated for chronic and uncontrolled pain. Of these, 47 (90%) remained in treatment at the time of the first follow-up, 2 had died, and 3 were receiving care elsewhere.
At the time of the second follow-up, 29 patients were still being treated. Of the 18 children who were not, 3 had died, 4 were receiving care elsewhere, 4 were in home hospice care, 6 had completed therapy, and 1 was lost to follow-up.
Methadone was used from the start. Before initiation, the median morphine equivalent daily dose in the patients was 38 mg. The median target-mediated drug disposition at the time of methadone therapy was 7.8 mg. The ratio of the 2 parameters, which represented the objective response rate, had a median value of 5.2, which indicated a good response concerning methadone-mediated pain relief.
As scored on a 5-point scale (0, not at all; 1, a little bit; 2 kind of; 3, quite a bit; 4, a lot), the children rated their pain as 3.59 at baseline, 1.80 at the first follow-up, and 1.18 at the second follow-up. Both follow-up rankings differed significantly from baseline (P < .0001). Parental assessment of pain was 3.46 at baseline, 1.35 at the first follow-up, and 1.04 at the second follow-up, with significant differences again evident from the baseline score (P < .0001).
Other improvements from baseline to the first and second follow-ups with the same 5-point scale included patient-rated insomnia (2.50 vs 1.07 [P = .005] and 1.06 [P < .001]), parent-rated insomnia (2.50 vs 1.07 [P < .001] and 1.26 [P < .001]), patient-rated fatigue (1.51 vs 1.53 [P = .22], and 1.48 [P = .05]), and parent-rated fatigue (1.93 vs 1.60 [P = .09] and 1.41 [P = .01]).
“Methadone significantly lowered parent- and child-reported outcomes of pain and remained effective over time,” said Dr. Madden. “Insomnia significantly improved without other interventions besides pain controls. Fatigue showed a trend to improve between baseline and follow-up 1 and significantly improved between follow-up 1 and 2.”
No change was made in the methadone dose in 79% of the patients. The dose needed to be increased in 5 patients (17.2%) who were tapering methadone due to resolution of the original pain syndrome and in 1 patient (3.45%) for adequate pain control. In all patients, methadone was tapered as the original pain resolved.
Methadone neurotoxicity did not occur, and no heart rate abnormalities were evident.
“Methadone is often relegated to being the long-acting opioid to use only after long-acting morphine, long-acting oxycodone, and fentanyl transdermal patches have proved ineffective in controlling pain,” said Dr. Madden. “We believe that methadone has a role as a safe and effective first long-acting opioid in children who have uncontrolled pain while only on immediate-release mu opioid agonists,” he concluded.
The results support the view of the MD Anderson clinicians and others that methadone is an attractive medication for treatment of chronic pain in children with advanced cancer because it is the only long-acting opioid available as a liquid, which allows for precise dose control. Another plus is that it is easy to swallow, which is not always the case with tablet medications in these patients. Additionally, it can be used in children unable to reliably swallow tablets.
[Presentation title: Methadone as the Initial Long-Acting Opioid in Children With Advanced Cancer. Abstract 224]