Article of the Month
Carla Ripamonti, MD
(Italy)
Patient-Controlled Methylphenidate for Cancer Fatigue: a double-blind, randomized, placebo-controlled trial
Author(s): Bruera E, Valer V, Driver L, Shen L, Willey J, Zhang T, Palmer J.L
Journal: J Clinical Oncology 2006; 24: 2073-8
Fatigue is a debilitating symptom that interferes with activity and life enjoyment in 60%-90% of advanced cancer patients. Fatigue is a multidimensional syndrome caused by a number of physical and psychosocial mechanisms and may be tumor-induced as well as drug induced.
Among the drugs used in the management of cancer fatigue, methylphenidate is a psycho stimulant already studied in a previous open-label study at the dose of 5 mg, every 2 hours, as needed. This uncontrolled study produced significant improvements in physical and functional subscores as determined by the Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) and in well-being and depression scores using the Edmonton Symptom Assessment System (ESAS).
The authors then carried out a double-blind RCT with the aim to evaluate the effectiveness of patient-controlled methylphenidate on fatigue when compared to a placebo.
Patients’ assessment consisted of using the ESAS and FACIT-F (Fatigue). FACIT-F score was the first end-point. Patients were enrolled if: 1. fatigue score was of at least 4 (0= no fatigue; 10= worst possible fatigue) during the previous day and for a further 4 days; 2. Mini Mental State Examination was normal (score ≥ 24/30); 3. Hb level was at least 10 g/dL; 4. there was an absence of glaucoma, severe anxiety disorders, tachycardia, uncontrolled hypertension, substance abuse and use of drugs such as MAO inhibitors, tricyclic antidepressants, and clonidine.
Patients were randomly assigned to receive either 5 mg methylphenidate or a placebo every 2 hours as needed for 7 days (max 4-5 capsules/day). Patients used a diary in which they scored their fatigue 4 times a day (before breakfast, lunch, dinner, bedtime). In addition, the patients received a daily call from a research nurse who asked questions to ensure the diaries were used to compile the data and to assess the tolerability of the treatment.
The main result of the study showed no significant difference in fatigue improvement in the methylphenidate group compared to the placebo group at 8 days after the beginning of the study for both FACIT-F scores as well as ESAS scores. No significant toxicity was observed.
The authors concluded that there is no indication for using methylphenidate regularly in clinical practice for the relief of cancer fatigue
Why I chose this article
The results obtained from this RCT compared to previous open label studies of the same drug, confirm the importance to perform placebo controlled studies to evaluate the control of subjective symptoms.
Another important aspect is the high percentage of positive results in the placebo group with respect to the 30% expected result when compared to the other studies performed by the same research group. However, as the authors underline in this study there is a potential “curative effect” due to the daily telephone calls made by the research nurses who were blindedwith respect to the treatment, but who were probably very effective because of the communication they had with the patients. How much did this attention to the patient contribute to a sensation of "feeling being taken care of" and did it influence the placebo effect and the methylphenidate effect?
Could it be that this study demonstrates that a compassionate approach (communication with and the feeling of patients of being considered and taken care of) could be just as effective as a medicine, at least in certain clinical situations?
Could this be the first evidence that less drugs and dosages and more human resources should be made available in the treatment of patients?
Is the sense of fatigue less if one feels taken into consideration and receives a telephone call to find out how he/she feels?
What's new in this article? A daily telephone call made by the research nurse, even on a Saturday and a Sunday is associated with the feeling that everything seems better. Probably the time has arrived to understand that in the Health Service there isn't only a need for drugs, but the application of more human resources should be favored and encouraged. Can this bring about a reduction in the cost of drug treatment?
I believe we are on the right track.
Thank you colleagues of M.D. Anderson, Houston, Texas.
Well done!!!!
Regards,
Carla Ripamonti, MD
Member of the Board of Directors, IAHPC
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