Another pilot study has confirmed that “scrambler” therapy is an effective, noninvasive treatment for various types of cancer-related neuropathic pain, including chemotherapy-induced peripheral neuropathy (CIPN). And as in several previous small trials, no adverse events were reported.
In scrambler therapy, electrocardiographic-like pads are placed around the area of pain. The device then synthesizes different types of nerve action potentials that deliver nonpain information through cutaneous nerves to the pain site. It is thought that scrambling afferent pain signals and replacing them with nonpain signals induces pain relief.
One such device, from Calmare Therapeutics, is cleared for use in both the United States and Europe. The Calmare device was named in honor of the Italian inventors, according to the manufacturer; in Italian, calmare means “to soothe or ease.”
Latest Study From South Korea
The latest study of the technique, by Sang Chul Lee, MD, PhD, from the National University Hospital College of Medicine in Seoul, South Korea, and colleagues, was published online December 28 in the European Journal of Oncology Nursing.
Dr Lee’s team reports that using the Calmare device to administer scrambler therapy for 10 consecutive days significantly reduced pain scores in patients with various types of cancer-related neuropathic pain, including CIPN. The therapy also improved quality of life and reduced the use of rescue opioids, although patients remained on background opioid pain management.
“Our results reinforce the idea that Calmare therapy is an effective tool for managing CIPN when it is refractory to standard medication, such as anticonvulsants, antidepressants, and/or opioid analgesics,” Dr Lee and his colleagues write.
The therapy “might be another treatment option to help manage intractable cancer-related neuropathic pain, including bone metastatic pain and postsurgical neuropathic pain,” they add.
“Prospective studies are recommended to confirm our findings and ascertain which additional cancer-related neuropathic pain can show a positive response to Calmare therapy,” they note.
The study was an open-label, single-group exploratory study designed to evaluate the effectiveness of scrambler therapy in various types of cancer-related neuropathic pain.
Patients were eligible for the study if they had cancer- or surgical-related neuropathic pain or mixed pain. Pain was classified as CIPN caused by metastatic bone lesions or postsurgical CIPN neuropathic pain.
All patients underwent baseline screening before therapy, and were then treated with 40 minutes of scrambler therapy each day for 10 consecutive days. Treatment response was assessed after 1 month.
The 20 patients who completed the 10-day course of scrambler therapy were evaluated at follow-up.
Regardless of the type of neuropathic pain being treated, scores on the 11-point Numerical Rating Scale (NRS) decreased significantly from baseline to 1-month follow-up (P < .001).
At follow-up, six patients reported a decrease in pain of at least 50%, nine reported a decrease of 30% to 50%, and five reported a decrease of less than 30%. So 15 patients (75%) experienced a reduction in pain of at least 30% pain, whereas no patient experienced an increase in pain, Dr Lee reported.
After the first week of treatment, NRS pain scores were significantly better (P < .001), and responses were sustained 2 weeks after the end of treatment.
Brief Pain Inventory scores were also significantly better at follow-up, and half the patients who finished the treatment course indicated they were slightly or moderately satisfied with the therapy.
The regular use of opioids did not change during the study period, but the need for rescue opioids dropped from a baseline dose of 5 mg to 0 mg at the end of the study, which was marginally significant (P = .050).
No adverse events that could have been associated with the therapy were reported.
Support for Scrambler Therapy
There have been a number of previous studies also reporting benefit.
In the United States, a team from the Massey Cancer Center at Virginia Commonwealth University in Richmond reported similar findings using the same cutaneous electrostimulation device for CIPN (J Pain Symptom Manage. 2010;40:883-891).
In that study, 16 patients with CIPN ranging in duration from 3 months to 8 years received 1 hour of scrambler therapy each day for 10 working days. On day 10, all but one of the patients reported a reduction in pain scores — from 5.8 at baseline to 2.3 at 10 days (P < .001). Four patients in this small pilot trial had their CIPN reduced to zero. Again, no toxicity was seen.
Some of the researchers from Virginia Commonwealth University also evaluated scrambler therapy in 39 cancer patients with chronic neuropathic pain (J Pain Palliative Care Pharmacother. 2013;27:359-364). Treatment was given once a day for 10 days over a 2-week period.
NRS scores dropped from 6.6 at baseline to 4.5 at 2 weeks, and remained at similar levels at 1, 2, and 3 months (p < .001). Clinically important and statistically significant improvements were seen in average, least, and worst pain scores, as well as in other measures of pain, the investigators note. No adverse effects were reported in this study either.
An Italian team compared guideline-based pharmacologic treatment with scrambler therapy given once daily for 10 days in 52 patients (J Pain Symptom Manage. 2012;43:87-95). The patients, who were matched by type of pain, had postsurgical neuropathic pain, postherpetic neuralgia, or spinal canal stenosis.
In the pharmacologic group, the mean visual analogue scale score dropped from 8.1 at baseline to 5.8 at 1 month, whereas in the scrambler group, it dropped from 8.0 at baseline to 0.7 at 1 month.
Some patients relapsed, but retreatment and maintenance therapy provided relief and, again, no adverse effects from treatment were observed.
Recent American Study
A recent study was a pilot evaluation of scrambler therapy in of 37 patients with CIPN by Charles Loprinzi, MD, PhD, from the Mayo Clinic in Rochester, Minnesota, and colleagues (Support Care Cancer. 2015 23:943-951). Patients had symptoms for at least 1 month before receiving scrambler therapy, and rated tingling, pain, or both 4 or higher on a 10-point scale during the week before therapy, which consisted of 10 daily 30-minute sessions.
After 10 days of treatment, Dr Loprinzi and his colleagues reported that average pain scores decreased by 53% from baseline (P < .0001) and tingling decreased by 44% (P < .0001). Patients also reported a 37% decrease in numbness (P = .0002).
Despite all these positive results, the uptake of scrambler therapy has been tentative, especially in light of the fact that few if any medications are effective in neuropathic pain. Dr Loprinzi explained that people have been slow to explore its use because scrambler therapy sounds too good to be true.
“People have claimed a lot of things to be beneficial for pain that do not end up coming through,” he told Medscape Medical News.
“I also think you could argue that studies that have been done on scrambler therapy have not been published in the most influential journals, and we do not have absolute proof from what we like to call placebo-controlled multi-institutional trials on scrambler therapy,” he added.
In fact, efforts to conduct larger trials are ongoing, but it takes time and money to do these trials, Dr Loprinzi noted.
“There is a learning curve associated with the use of scrambler therapy,” he added. Most practitioners who offer the treatment have undergone training in Italy. There is a real technique to giving maximally effective therapy.
“The first 25% of our patients did not do as well as the last 75% of our patients, so it’s not the same as taking a pill,” Dr Loprinzi reported. “It takes time to train a person to give it and it takes time for patients to get it, so all these issues come into play.”
Scrambler therapy was not originally developed for the treatment of cancer-related neuropathic pain. Rather, it was developed for chronic pain and, indeed, has been used in many patients with noncancer-related pain, including low back pain, Dr Loprinzi pointed out. But he foresees it having wide applications.
“I have been involved with the treatment of hundreds of patients and I am a believer that scrambler therapy works,” Dr Loprinzi told Medscape Medical News.
This study was sponsored by GEOMC Co. Ltd. Dr Loprinzi reports serving in a consulting or advisory role for Helsinn Therapeutics and receiving research funding from Pfizer.
Eur J Oncol Nurs. Published online December 28, 2015. AbstractJanuary 12, 2016