Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial

Abstract

Purpose Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. Patients and Methods Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. Results In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. Conclusion This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

Nursing intervention to enhance outpatient chemotherapy symptom management: Patient‐reported outcomes of a randomized controlled trial

“…23 Psychostimulants have demonstrated mixed efficacy for improving fatigue, [24][25][26] and can cause additional problems such as agitation or low appetite. 27 The results of the current study support the importance of advancing the science of fatigue and other complex symptoms that occur within the context of cancer treatments.…”

Sick and Tired: Mood, Fatigue, and Inflammation in Cancer

“…A more recent meta-analysis of methylphenidate treatment for cancerrelated fatigue included five studies (n=426) and demonstrated benefit of methylphenidate over placebo, though with a small effect size [63]. Subsequently, two larger studies of methylphenidate have failed to demonstrate benefit over placebo for cancer-related fatigue [64,65]; but like the aforementioned modafanil study, a subset analysis demonstrated benefit for those patients with severe fatigue and/or advanced disease [65]. Thus, the data is limited regarding the efficacy of pharmacologic treatments for fatigue in cancer.…”

Use of methylphenidate in palliative patients with asthenia: a review

“…Hardy revisa los efectos secundarios de estudios que versan sobre metilfenidato entre 1956 y 2009. Los más frecuentemente descritos son el nerviosismo/insomnio y anorexia 8,16,19 , taquicardia-palpitaciones, mareo-confusión 8,19 . Otros como cefalea o diarrea/dolor abdominal 15 pueden llegar a presentarse hasta en un 63% de los casos (siendo el estudio de Roth 9 , el más reciente EC con mayor incidencia de efectos secundarios).…”