A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer.

BACKGROUND: Women who receive adjuvant chemotherapy for breast cancer develop fatigue, and a subset reports cognitive impairment. Methylphenidate is reported to improve fatigue and to decrease cognitive impairment in other populations. MATERIALS AND METHODS: Women were randomised early during their chemotherapy to receive d-methylphenidate (d-MPH), a form of methylphenidate, or an identical appearing placebo. All participants took placebo for one cycle to ensure compliance and then study medication until completion of chemotherapy. Subjects were assessed at baseline, end of chemotherapy and at approximately 6 months follow-up with the High Sensitivity Cognitive Screen (HSCS) and the Hopkins Verbal Learning Test-Revised (HVLT-R). They also completed the self-report Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-F (F = fatigue) questionnaires, evaluating quality of life and fatigue. RESULTS: A total of 57 evaluable women were randomised: 29 to d-MPH and 28 to placebo; the study did not meet its accrual goal of 170 patients, mainly because women were reluctant to take additional medication in general and methylphenidate in particular. Groups were well matched for age (median, 50 years) and education. d-MPH and placebo were well tolerated. There were no significant differences between the randomised groups in classification of cognitive function by HSCS or in summed FACT-F fatigue scores (the primary endpoints of the study) at any of the assessments. There were also no differences in HLTV-R scores or quality of life. CONCLUSIONS: This study is underpowered, but there are no trends to suggest that d-MPH, taken concurrently with adjuvant chemotherapy, improves quality of life or fatigue.

Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study.

PURPOSE: We previously evaluated fatigue, menopausal symptoms, and cognitive dysfunction in patients receiving adjuvant therapy for breast cancer and matched healthy women. Here we report assessment of these women 1 and 2 years later. PATIENTS AND METHODS: Patients without relapse and controls were evaluated by the Functional Assessment of Cancer Treatment-General Quality of Life questionnaire, with subscales for fatigue and endocrine symptoms, and by the High Sensitivity Cognitive Screen. RESULTS: There were 104, 91, and 83 patients and 102, 81, and 81 controls assessed at baseline and at 1 and 2 years, respectively. Median Functional Assessment of Cancer Treatment-Fatigue scores (range, 0 to 52) for patients improved from 31 (on chemotherapy) to 43 and 45 at 1 and 2 years, respectively, but were stable in controls (46 to 48). Median Functional Assessment of Cancer Treatment-Endocrine Symptoms scores (range, 0 to 72) for patients improved from 57 (on chemotherapy) to 59 and 61 at 1 and 2 years, respectively, and were stable in controls (64 to 65). Differences between patients and controls remained significant for these scales. The incidence of moderate-severe cognitive dysfunction by the High Sensitivity Cognitive Screen decreased in patients from 16% (on chemotherapy) to 4.4% and 3.8% and in controls from 5% to 3.6% and 0% at 1 and 2 years, respectively. There were minimal differences between estrogen receptor-positive patients who started hormonal therapy (mainly tamoxifen) after chemotherapy and estrogen receptor-negative patients who did not. Differences in quality of life between patients and controls were significant only at baseline. CONCLUSION: Fatigue, menopausal symptoms, and cognitive dysfunction are important adverse effects of chemotherapy that improve in most patients. Hormonal treatment has minimal impact on them.

Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer.

PURPOSE: There is evidence that cognitive dysfunction, fatigue, and menopausal symptoms may occur in women receiving adjuvant chemotherapy for breast cancer. Here, we determine their incidence and severity, and interrelationships between them and quality of life. PATIENTS AND METHODS: In this study, 110 women receiving adjuvant chemotherapy each nominated a female relative, friend, or neighbor (matched by age) as a control; 100 eligible matched pairs were evaluated. Patients and controls completed the following assessments: the High-Sensitivity Cognitive Screen, and the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life scale with subscales for fatigue (FACT-F) and endocrine symptoms (FACT-ES). They also performed tests of attention and reaction time. RESULTS: Patients and controls were well matched for age and level of education. There was a higher incidence of moderate or severe cognitive impairment in the patient group (16% v 4%; P =.008). Patients experienced much more fatigue than controls (median FACT-F scores, 31 v 46; P <.0001) and more menopausal symptoms (median FACT-ES scores, 58 v 64; P <.0001). Self-reported quality of life of the patients was poorer than for controls, especially in physical and functional domains (median FACT-G scores, 77 v 93; P <.0001). There was strong correlation between fatigue, menopausal symptoms, and quality of life (P <.0001 for each pair), but none were significantly associated with the presence of cognitive dysfunction. CONCLUSION: Adjuvant chemotherapy causes cognitive dysfunction, fatigue, and menopausal symptoms in women with breast cancer. Priority should be given to the study of strategies that might reduce these toxic effects.