Kannarkat G, Lasher EE, Schiff D.

Neurologic complications of chemotherapy agents 

Curr Opin Neurol. 2007 Dec;20(6):719-25. Review.PMID: 17992096 [PubMed – indexed for MEDLINE]

PURPOSE OF REVIEW: To review neurologic complications of common and recently developed chemotherapeutic agents, as well as recent research regarding ‘chemobrain’. RECENT FINDINGS: Bortezomib, a new anticancer agent, has a propensity toward causing a largely sensory and reversible peripheral neuropathy. Infusion of magnesium and calcium pre and post-oxaliplatin infusion reduces neuropathy but may interfere with clinical response to oxaliplatin. No other measures currently reduce the incidence or severity of neuropathy related to platinum compounds, taxanes, or thalidomide. Chemobrain, cognitive decline attributed to chemotherapy, has garnered research interest. Prevalence and epidemiology of chemobrain are poorly understood. Potential underlying mechanisms are under investigation in animal models and include effects on long-term potentiation and cerebral blood flow. Blood-brain barrier permeability, efficiency of cellular efflux pumps, DNA damage, telomere shortening, alteration of cytokine regulation, defects in neural repair, and oxidative stress may play roles in the effects of chemotherapy on central nervous system function. SUMMARY: Data on prevention and treatment of chemotherapy-induced peripheral neuropathy are limited. Calcium and magnesium infusions for oxaliplatin administration have the most scientific support and are widely used in practice but may interfere with the clinical efficacy of oxaliplatin. Some novel agents, particularly bortezomib, have significant risk of chemotherapy-induced peripheral neuropathy. Animal models are beginning to reveal the mechanisms underlying the impact of individual chemotherapeutic drugs on cognition.

Taillibert S, Voillery D, Bernard-Marty C.

Chemobrain: is systemic chemotherapy neurotoxic?

Curr Opin Oncol. 2007 Nov;19(6):623-7. Review. PMID: 17906463 [PubMed – indexed for MEDLINE]

PURPOSE OF REVIEW: The existence of chemobrain has become almost universally accepted, although many details of the concept are controversial. Data about the different types of cognitive impairment and their duration are not always consistent in the literature. We still do not know which cytotoxic agents are responsible, which characteristics make patients vulnerable, and which biologic mechanisms are involved. RECENT FINDINGS: Through this review of the recent literature, we provide an actualized definition of chemobrain including recent functional imaging data and we debate its controversial aspects. Potential causes such as oxidative stress and their potential clinical application in the prevention and treatment of chemobrain are also discussed. Eventually, the methodological aspects of published studies are questioned and propositions are provided in order to improve the design of future trials. SUMMARY: This issue is of clinical importance given the prevalence of breast carcinoma, the increased use of chemotherapy as adjuvant therapy, the increasing use of more aggressive dosing schedules, and the increasing survival rates. Better designed future trials should lead to a better definition and understanding of chemobrain and to future therapies.

Hurria A, Somlo G, Ahles T.
Renaming “chemobrain”.

Cancer Invest. 2007 Sep;25(6):373-7. Review. PMID: 17882646 [PubMed – indexed for MEDLINE]

A subset of breast cancer survivors are reporting cognitive impairment after cancer treatment, which has commonly been attributed to the receipt of chemotherapy and colloquially termed “chemobrain.” For some, a fear of this side effect enters into their decision regarding therapy. Our review of the literature reveals that so-called “chemobrain” is complex and that factors other than chemotherapy may affect cognitive function, including the impact of surgery and anesthesia, hormonal therapy, menopause, anxiety, depression, fatigue, supportive care medications, genetic predisposition, comorbid medical conditions, or possibly paraneoplastic phenomenon. Studies to date have differed in their assessment and definition of cognitive impairment, thus, making comparisons between studies difficult. In addition, most studies have been limited by a small sample size, and there has been a general lack of focus on older patients despite their high concentration within the cancer population. Large, multicenter studies are needed to better understand the magnitude and mechanism of cognitive changes in cancer survivors and to assess the impact of cognitive changes on the patient’s daily lives. We propose that the phenomenon commonly referred to as “chemobrain” would be more accurately labeled “cancer- or cancer-therapy-associated cognitive change.”

Nelson CJ, Nandy N, Roth AJ.
Chemotherapy and cognitive deficits: mechanisms, findings, and potential interventions.

Palliat Support Care. 2007 Sep;5(3):273-80. Review. PMID: 17969831 [PubMed – indexed for MEDLINE]

“Chemobrain” is the phenomenon of cognitive decline some patients may experience after chemotherapy. Current research indicates the cognitive domains that may be most impacted by chemotherapeutic agents are visual and verbal memory, attention, and psychomotor functioning. These cognitive deficits can have an effect on a patient’s ability to make informed treatment decisions, pursue occupational or academic pursuits, and his or her overall quality of life. The potential mechanisms that cause this disruption remain largely unknown, although contributing factors could be vascular injury and oxidative damage, inflammation, direct injury to neurons, autoimmune responses, chemotherapy-induced anemia, and the presence of the apolipoprotein E epsilon4 (APOE epsilon 4) gene. Interventions to help alleviate the symptoms of chemobrain could include nonpharmacologic treatment such as antioxidants and cognitive-behavioral therapy. In addition, patients may benefit from pharmacologic treatment such as recombinant human erythropoietin and psychostimulant drugs such as methylphenidate. It is important to note that the proposed therapeutics treat the symptoms of chemobrain based on the hypothesized mechanisms. Therefore, a detailed understanding of the mechanisms that cause chemobrain, as well as a comprehension of what specific cognitive domains are impacted, is crucial in developing more specific treatments to improve patients’ cognitive functioning and overall quality of life.