Methylphenidate May Improve Fatigue in Some Advanced Cancer
Methylphenidate May Improve Fatigue in Some Advanced Cancer
July 20, 2010 — The stimulant methylphenidate does not significantly decrease cancer-related fatigue, according to the results of a phase 3 study published online July 12 in the Journal of Clinical Oncology.
However, the drug was more beneficial than placebo to patients with more advanced fatigue and/or more advanced disease, but these findings of a benefit came from a subset analysis within the study and therefore are not fully proven.
Methylphenidate, which is marketed as Ritalin, among other trade names, is approved by the US Food and Drug Administration for the treatment of attention deficit hyperactivity disorder and narcolepsy.
Previous Evidence of Benefit
The trial of cancer-related fatigue evaluated a 54 mg/day dose of long-acting methylphenidate in a heterogeneous population of 148 cancer patients, according to the study authors, led by Amanda Moraska, MD, from the Mayo Clinic in Rochester, Minnesota, and the North Central Cancer Treatment Group.
This is not the first time that research has suggested that patients with advanced cancer and/or advanced fatigue would benefit from methylphenidate, according to an editorial accompanying the study.
Editorialists Eduardo Bruera, MD, and Sriram Yennurajalingam, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, say that a previous study, led by Dr. Bruera, found that "higher levels of fatigue were predictors of response to methylphenidate in patients with advanced cancer" (J Clin Oncol. 2006;24:2073-2078).
Dr. Bruera said that he and his colleagues use methylphenidate in their oncology practice.
In advanced cancer patients with severe fatigue we frequently try methylphenidate.
"In advanced cancer patients with severe fatigue we frequently try methylphenidate, particularly in patients who are also on opioids, because opioid sedation is a contributor to fatigue in these patients. Patients with depressive symptoms can also benefit from methylphenidate," he told Medscape Medical News.
However, the senior author of this new study does not encourage other oncologists to use methylphenidate.
I cannot recommend methylphenidate.
"I cannot recommend methylphenidate. It caused toxicities and had no clear benefit. Having said this, I can understand how some physicians would decide to treat patients with this," Charles Loprinzi, MD, from the Mayo Clinic, told Medscape Medical News.
Reach Out and Touch Someone
Drs. Bruera and Yennurajalingam do not believe that any single intervention, including methylphenidate, is the best approach to managing fatigue.
"Fatigue is a complex multidimensional symptom, and it is therefore unlikely to be successfully managed with single pharmacologic or nonpharmacologic interventions," they write.
The editorialists recommend combination therapy.
"Patients are likely to require a combination of counseling, increased physical activity, correction of hormonal and metabolic abnormalities, and pharmacologic interventions aimed at body composition, inflammation, and brain function."
However, it is not known how to determine which patients need which specific interventions for optimal management of fatigue, they say.
Nevertheless, Drs. Bruera and Yennurajalingam point to counseling in the form of phone calls from oncology nurses as a potential difference maker.
They note that in the 2006 study led by Dr. Bruera, patients "received regular phone calls from nurses for the assessment of their symptoms, and this may have had a major symptomatic effect."
Phone calls can be mood changing, suggested Dr. Bruera.
Ideally all palliative-care programs should have a phone-care program.
"Fatigue is a symptom and most symptoms are strongly influenced by mood. We believe that the phone call is supportive for patients emotionally, and that results in improvement in a number of symptoms, including fatigue. Ideally all palliative-care programs should have a phone-care program," he said.
A "telecare" program that included phone calls to patients from oncology nurses improved 2 other common cancer symptoms, depression and pain, according to a recent study reported by Medscape Medical News.
Study Results
The latest study of methylphenidate was conducted in 148 adults with a variety of cancers and stages of cancer, and the drug was compared with placebo over a period of 4 weeks.
Participants took one 18 mg tablet a day for the first week; 2 tablets a day for the second week, and 3 tablets a day for the third and fourth weeks, so that they reached the goal dose of 54 mg/day by the final 2 weeks of the study.
The Brief Fatigue Inventory, which asks about "usual fatigue," was the primary outcome measure; the secondary outcome measures consisted of a variety of quality-of-life measures, including ones for sleep and vitality.
Using an area under the serum concentration–time curve analysis, the investigators found that methylphenidate, compared with placebo, did not significantly improve the primary end point of cancer-related fatigue in this patient population over the 4 weeks (P = .35).
Comparisons between the treatment and placebo groups of secondary end points were also negative, report the authors.
A subset analysis suggested that patients with more severe fatigue and/or with more advanced disease had some fatigue improvement with methylphenidate.
In the analysis, change in usual fatigue from baseline was evaluated on the basis of fatigue severity at baseline and stage of disease.
In advanced-stage disease (III or IV), the mean improvement in the usual fatigue score was 19.7 with methylphenidate and 2.1 with placebo (P = .02).
Also, for those patients with the highest levels of worst fatigue (score of 8 to 10) at baseline, the mean change in usual fatigue was 26 with methylphenidate and 16 with placebo; however, this difference was not statistically significant, report the authors.
Toxicities are a concern with this drug, and there was a significant difference between the study groups in self-reported toxicities, with increased levels of nervousness and appetite loss in the methylphenidate group.
The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online July 12, 2010. Abstract, Abstract
July 20, 2010 — The stimulant methylphenidate does not significantly decrease cancer-related fatigue, according to the results of a phase 3 study published online July 12 in the Journal of Clinical Oncology.
However, the drug was more beneficial than placebo to patients with more advanced fatigue and/or more advanced disease, but these findings of a benefit came from a subset analysis within the study and therefore are not fully proven.
Methylphenidate, which is marketed as Ritalin, among other trade names, is approved by the US Food and Drug Administration for the treatment of attention deficit hyperactivity disorder and narcolepsy.
Previous Evidence of Benefit
The trial of cancer-related fatigue evaluated a 54 mg/day dose of long-acting methylphenidate in a heterogeneous population of 148 cancer patients, according to the study authors, led by Amanda Moraska, MD, from the Mayo Clinic in Rochester, Minnesota, and the North Central Cancer Treatment Group.
This is not the first time that research has suggested that patients with advanced cancer and/or advanced fatigue would benefit from methylphenidate, according to an editorial accompanying the study.
Editorialists Eduardo Bruera, MD, and Sriram Yennurajalingam, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, say that a previous study, led by Dr. Bruera, found that "higher levels of fatigue were predictors of response to methylphenidate in patients with advanced cancer" (J Clin Oncol. 2006;24:2073-2078).
Dr. Bruera said that he and his colleagues use methylphenidate in their oncology practice.
In advanced cancer patients with severe fatigue we frequently try methylphenidate.
"In advanced cancer patients with severe fatigue we frequently try methylphenidate, particularly in patients who are also on opioids, because opioid sedation is a contributor to fatigue in these patients. Patients with depressive symptoms can also benefit from methylphenidate," he told Medscape Medical News.
However, the senior author of this new study does not encourage other oncologists to use methylphenidate.
I cannot recommend methylphenidate.
"I cannot recommend methylphenidate. It caused toxicities and had no clear benefit. Having said this, I can understand how some physicians would decide to treat patients with this," Charles Loprinzi, MD, from the Mayo Clinic, told Medscape Medical News.
Reach Out and Touch Someone
Drs. Bruera and Yennurajalingam do not believe that any single intervention, including methylphenidate, is the best approach to managing fatigue.
"Fatigue is a complex multidimensional symptom, and it is therefore unlikely to be successfully managed with single pharmacologic or nonpharmacologic interventions," they write.
The editorialists recommend combination therapy.
"Patients are likely to require a combination of counseling, increased physical activity, correction of hormonal and metabolic abnormalities, and pharmacologic interventions aimed at body composition, inflammation, and brain function."
However, it is not known how to determine which patients need which specific interventions for optimal management of fatigue, they say.
Nevertheless, Drs. Bruera and Yennurajalingam point to counseling in the form of phone calls from oncology nurses as a potential difference maker.
They note that in the 2006 study led by Dr. Bruera, patients "received regular phone calls from nurses for the assessment of their symptoms, and this may have had a major symptomatic effect."
Phone calls can be mood changing, suggested Dr. Bruera.
Ideally all palliative-care programs should have a phone-care program.
"Fatigue is a symptom and most symptoms are strongly influenced by mood. We believe that the phone call is supportive for patients emotionally, and that results in improvement in a number of symptoms, including fatigue. Ideally all palliative-care programs should have a phone-care program," he said.
A "telecare" program that included phone calls to patients from oncology nurses improved 2 other common cancer symptoms, depression and pain, according to a recent study reported by Medscape Medical News.
Study Results
The latest study of methylphenidate was conducted in 148 adults with a variety of cancers and stages of cancer, and the drug was compared with placebo over a period of 4 weeks.
Participants took one 18 mg tablet a day for the first week; 2 tablets a day for the second week, and 3 tablets a day for the third and fourth weeks, so that they reached the goal dose of 54 mg/day by the final 2 weeks of the study.
The Brief Fatigue Inventory, which asks about "usual fatigue," was the primary outcome measure; the secondary outcome measures consisted of a variety of quality-of-life measures, including ones for sleep and vitality.
Using an area under the serum concentration–time curve analysis, the investigators found that methylphenidate, compared with placebo, did not significantly improve the primary end point of cancer-related fatigue in this patient population over the 4 weeks (P = .35).
Comparisons between the treatment and placebo groups of secondary end points were also negative, report the authors.
A subset analysis suggested that patients with more severe fatigue and/or with more advanced disease had some fatigue improvement with methylphenidate.
In the analysis, change in usual fatigue from baseline was evaluated on the basis of fatigue severity at baseline and stage of disease.
In advanced-stage disease (III or IV), the mean improvement in the usual fatigue score was 19.7 with methylphenidate and 2.1 with placebo (P = .02).
Also, for those patients with the highest levels of worst fatigue (score of 8 to 10) at baseline, the mean change in usual fatigue was 26 with methylphenidate and 16 with placebo; however, this difference was not statistically significant, report the authors.
Toxicities are a concern with this drug, and there was a significant difference between the study groups in self-reported toxicities, with increased levels of nervousness and appetite loss in the methylphenidate group.
The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online July 12, 2010. Abstract, Abstract
Source...