The pathophysiologic roots of cancer-related fatigue (CRF) remain poorly understood, but CRF is a pervasive problem, affecting the vast majority of patients with cancer and frequently persisting for months or even years after treatment. CRF is debilitating and can profoundly impact a patient’s quality of life; its severity correlates with depression and prognosis. Yet patients do not always raise concerns about their fatigue with clinicians. Although the evidence base for managing CRF is relatively small, physical exercise and dexamethasone appear to be helpful interventions. Communication with patients about CRF symptoms and treatment options might improve detection and assessment.

Cancer-related fatigue is defined as persistent tiredness, weakness or exhaustion that interferes with a patient’s ability to function physically, emotionally, cognitively, or socially.1,2 Patients report that CRF is both physically debilitating and socially isolating—more so even than pain or nausea.3

“CRF is associated with decreased survival and interferes with employment, enjoyment of life, relationships, and motivation to battle the cancer,” notes Tami Borneman, RN, MSN, CNS, FPCN, of the City of Hope Cancer Center, in Duarte, California.4

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CRF onset can precede treatment, but clearly becomes more acute in many patients undergoing traditional anticancer therapies; symptoms persist for months or years in a third of cancer survivors, studies suggest.1,5 A recent study found that 45% of patients undergoing active anticancer treatment report moderate to severe CRF.5 CRF is also being reported by patients receiving targeted therapies such as sunitinib (Sutent, generic).6 With improving survival times for cancer patients, CRF among patients undergoing treatment and survivors seems unlikely to wane—and might well become even more common in the near future.

RELATED: New clinical guidelines developed for cancer-related fatigue

Despite its impact, however, patients do not always volunteer that they are experiencing CRF, and clinicians do not always ask. For example, documenting fatigue in the patient’s medical record is uncommon.4 As a result, CRF is believed to be underdetected and undertreated.1,4

CRF is typically measured via patient self-report using a scale of 0 to 10 (0 representing no fatigue, and 10 representing severe fatigue), although several formal instruments have been developed and validated (eg, the Brief Fatigue Inventory [BFI] and the Functional Assessment of Cancer Therapy Instrument-Fatigue [FACIT-F] scale).4,7 The National Comprehensive Cancer Network (NCCN) recommends all patients with cancer be assessed for CFR at diagnosis and at each chemotherapy appointment.2


Contributing factors include comorbidities, radiation therapy, chemo- and targeted anticancer therapies, surgery, and polypharmacy.4 The underlying pathophysiologic underpinnings of CRF are poorly understood, although various lines of evidence implicate central nervous system neuroendocrine-immune inflammatory processes, including proinflammatory cytokines, and suggest that peripheral (muscular) fatigue does not play as important a role.1,8-11  Cytokine antagonists were recently proposed as a potential pharmacotherapy for CRF.10

Genotype and gene expression research underway includes work on the role of proinflammatory cytokine gene variants in CRF associated with breast cancer.1,10 If early findings are confirmed in larger studies, genotyping might allow meaningful stratification of patients by risk for CRF, and identify targets for drug development.10