Minton, O., Richardson, A., Sharpe, M., Hotopf, M., & Stone, P. (2008). A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. JNCI: Journal of the National Cancer Institute, 100, 1155–1166.

To examine the role of methylphenidate and other drugs in the management of cancer-related fatigue

DATABASES: Cochrane Register of Controlled Trials, EMBASE, and hand searching of several journals and reference lists

KEYWORDS: neoplasms or cancer or carcinoma or tumour, bone marrow transplant, neutropenia, radiotherapy, fatigue. Complete listing of search terms is provided.

INCLUSION CRITERIA:

• Randomized controlled trial
• Designed to test a drug against placebo or usual care
• Use of a multi-item measure of fatigue

EXCLUSION CRITERIA:

• Measure of fatigue with single-item tool or visual analog scale

TOTAL REFERENCES RETRIEVED: Initial searching provided 5,841 articles and abstracts for screening. One hundred sixteen were reviewed in detail.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were done from 1992–2007. Data were collected from studies on a standard form by two independent reviewers, and any differences were resolved by consensus.

FINAL NUMBER STUDIES INCLUDED = 27

SAMPLE RANGE ACROSS STUDIES = 12–939

TOTAL PATIENTS INCLUDED IN REVIEW: 6,568 

KEY SAMPLE CHARACTERISTICS: Samples included a variety of tumor types, a variety of treatments, and patients in active treatment as well as after treatment.

Erythropoietin

Ten trials were included in meta-analysis.

• Dosages ranged from 3,000–40,000 units, and frequency varied.
• After 12 weeks of treatment, there was a significant reduction of fatigue (Z = 8.32, p <.001, SMD = -.038).
• Most patients were anemic.
• Half of the studies were open label.

Darbepoetin

Four trials were included in meta-analysis.

• After 12 weeks of treatment, there was a significant effect compared with placebo (Z = 1.96, p = .05, SMD = -0.13).
• All patients were anemic.

Paroxetine

Two studies were included.

• After eight weeks of treatment, there was no fatigue benefit (Z = 1.06, p = -.29, SMD = -0.08).

Progestational Steroids

Four studies were included—three with megestrol acetate and one with medroxyprogesterone acetate.

• After an average of eight weeks of treatment, no benefit was seen (Z = 1.06, p = .29, SMD = -0.18).
• There was substantial heterogeneity among trials.
• There was a consistent negative effect across all trials.

Methylphenidate

Two studies were included.

• There was no overall benefit (Z = 0.63, p = .53).

Single studies

• One study on 12 patients reported a significant effect of etanercept, an inhibitor of tumor necrosis factor.
• One study on 466 women with metastatic breast cancer reported a significant effect of ibandronate compared with placebo.

Findings suggest that there is no overall, effective pharmacologic management of cancer-related fatigue. Meta-analysis of progestational steroids report an overall negative effect, suggesting that this approach is counterproductive for fatigue management.

• There is some expected bias in results due to lack of complete study data in some trials.
• Overall effect sizes reported are small, so, though statistically significant, the actual effectiveness in the patient experience is unclear.

The majority of patients who were treated with hematopoietic growth factors were anemic, pointing to the need to correct anemia, rather than any direct effect on the symptom of fatigue. These results point to the need to clinically evaluate such potential causes of fatigue. Even in these cases, the effect size is relatively small.