Fatigue is defined as a condition of exhaustion that does not improve with rest [9].

Fatigue is both an acute and a chronic complication of cytotoxic chemotherapy that is more common with increasing age [10] and may represent a major cause of functional dependence.

In older individuals, fatigue is a cause of deconditioning [11], functional dependence [12, 13], and increased mortality [14].

Any serious attempt to rehabilitate older cancer patients should include a plan to prevent and overcome fatigue.

The causes and the mechanisms of fatigue are largely unknown. It is clear that fatigue is associated with chronic inflammation and sarcopenia and may be improved with the correction of anemia in some patients [15].

Beside the cancer itself, which is one of the causes of fatigue in those patients with active disease, among other presumptive causes of fatigue, there are chemotherapy, as well as polipharmacy and sleep disorders [16].

The management of fatigue is paramount to the functional rehabilitation of older patients. This involves both prevention and timely treatment.

As some recent studies highlighted, fatigue is associated with functional dependence [12, 13] and death [14] in older individuals. Thus the management of fatigue is critical to rehabilitation.

Another important concern in older patients undergoing chemotherapy is the possible role of chemotherapy as a cause of dementia. Though the evidence supporting this association is inconclusive [17, 18], it is well known that chemotherapy may lead to some form of cognitive decline and that older people are at particular risk for this complication [19, 20].

Deconditioning is a common complication of prolonged hospitalization and prolonged inactivity in elderly individuals [11]. Older cancer patients are at particular risk of prolonged hospitalization from surgical and medical complications as well as of prolonged at home inactivity due to fatigue and malnutrition. Several controlled trials have assessed the prevention of deconditioning with exercise and home interventions, in particular the role of exercise and nutrition [21, 22].

Older individuals are at increased risk for long-term toxicity of chemotherapy. Among others, we acknowledge and include chronic cardiomyopathy from anthracyclines [23] and peripheral neuropathy [3].

Both sensory and motor neuropathies are a common complication of the treatment with platinum salts, vinca alkaloids, taxanes, and eribulin. Such complication is more frequent in older patients, and it may become chronic and irreversible.

At present an empiric approach to such problems includes careful cardiological baseline and follow-up evaluations, discontinuance of chemotherapy in the presence of early signs of toxicity, cardiological treatment for cardiomyopathy, and early rehabilitation of neurologic deficits.

It is of utmost importance to adopt all supportive measures in order to successfully treat vulnerable and unfit elderly patients with cancer and to reduce the risk of functional impairment.

In particular, it is important to rule out anemia and possible causes of anemia and correct them whenever possible in order to reduce anemia-associated fatigue and to choose cytotoxics according to expected acute and chronic adverse events [24].

Several important issues still need to be addressed in the field of rehabilitation of older cancer patients, in particular whether cancer and its treatment accelerate the physiologic aging of a person and whether nutritional interventions, exercise, and management of anemia have a role in preventing the long-term complications of cancer and its treatment and the long-term social implications of cancer and its treatment.

Primary brain tumors account for 1% of all cancers in adults and affect 5–13 per 100,000 population worldwide annually. In the last years, the overall incidence of brain tumors has increased, especially in elderly patients in which the incidence has doubled; moreover, 20–40% of patients with cancer develops nervous system (NS) metastases [25].

A wide variety of impairments of nervous system function may result from cancer, either by direct effect at the primary or metastatic tumor site or as a treatment consequence, such as neurosurgery, chemotherapy, radiation therapy, and corticosteroids, alone or in combination. Some of the most adverse effects associated with these treatments include fatigue, myopathy, insomnia, and mood disturbance. Anticonvulsant medications may further accentuate fatigue and somnolence.