A Randomized, Double-blind, 2-Period, Placebo-Controlled... : The Cancer Journal (original) (raw)

Original Articles

A Randomized, Double-blind, 2-Period, Placebo-Controlled Crossover Trial of a Sustained-Release Methylphenidate in the Treatment of Fatigue in Cancer Patients

Escalante, Carmen P. MD*; Meyers, Christina PhD*; Reuben, James M. PhD*; Wang, Xuemei MS*; Qiao, Wei MS*; Manzullo, Ellen MD*; Alvarez, Ricardo H. MD*; Morrow, Phuong Khanh MD†; Gonzalez-Angulo, Ana M. MD*; Wang, Xin Shelley MD*; Mendoza, Tito PhD*; Liu, Wenli MD*; Holmes, Holly MD*; Hwang, Jessica MD*; Pisters, Katherine MD*; Overman, Michael MD*; Cleeland, Charles PhD*

From the *The University of Texas MD Anderson Cancer Center, Houston, TX; and †Hematology/Oncology Therapeutic Area, Amgen, Thousand Oaks, CA.

All participants signed the institutional review board–approved study informed consent.

Grant funding was provided by Ortho-McNeil Janssen Scientific Affairs, LLC.

This work was presented as a poster at the 2012 Annual American Society of Clinical Oncology meeting in Chicago, IL.

Conflicts of Interest and Source of Funding: C.P.E. has received funding from Teva Pharmaceuticals. P.K.M. has a leadership position and stock ownership at Amgen. C.C. is a consultant at Amgen and has received remuneration from Amgen. For the remaining authors, none were declared.

Reprints: Carmen P. Escalante, MD, 1400 Pressler St, Unit 1465 Houston, TX 77030. E-mail: [email protected].

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Abstract

Purpose

This study assessed the efficacy of methylphenidate versus placebo for cancer-related fatigue reduction. Other objectives were to analyze cytokine levels and to determine the effects of methylphenidate on other symptoms, cognitive function, work yield, and patients’ perceptions and preferences.

Methods

Patients were randomly assigned (1:1) to receive methylphenidate-placebo or placebo-methylphenidate for 4 weeks. Patients crossed over after 2 weeks. Wilcoxon signed rank tests and McNemar tests were used to assess continuous and categorical variables. The primary efficacy endpoint was change in the level of worst fatigue on the Brief Fatigue Inventory (BFI) at the end of each 2-week period.

Results

The mean baseline BFI score was moderate (5.7). Methylphenidate treatment did not affect patients’ worst level of fatigue or other symptoms. Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the Hopkins Verbal Learning Test with BFI interference questions and BFI activity questions showed significant improvement in the methylphenidate-treated patients’ verbal learning, memory, visual perception, analysis, and scanning speed. Patients treated with methylphenidate missed significantly fewer work hours owing to health reasons and worked significantly more hours. After 4 weeks, 64% of patients reported that methylphenidate improved their cancer-related fatigue, and 58% wanted to continue treatment. Significant difference in interleukin 6R (positive), interleukin 10 (negative), and tumor necrosis factor α (positive) was noted between the methylphenidate and the placebo group.

Conclusions

Low-dose methylphenidate did not improve cancer-related fatigue. Patients taking methylphenidate had better cognition and were able to work more hours. Patients tolerated methylphenidate well, and the majority felt better and wanted to continue treatment.

© 2014 by Lippincott Williams & Wilkins