Chemotherapy may affect aspects of neuropsychological function.

LOS ANGELES -- Cancer patients call it "chemobrain"--a soggy mental state that seems to be a frequent side effect of chemotherapy.

It is rarely studied and poorly understood, but as the number of cancer survivors grows, the impact of chemotherapy on cognitive function will become an increasingly important concern, Curley Bonds, M.D., said at a review of psychiatry and psychopharmacology update sponsored by the University of California, Los Angeles.

Chemotherapy has been reported to affect several aspects of neuropsychological function. The components most commonly affected are focus and concentration, verbal and executive function, and motor activity, said Dr. Bonds of the university.

Several issues complicate research in this area.

One is sorting out the impact of chemotherapy from the effect of the cancer itself and that of other forms of therapy. Fatigue, anxiety, and depression commonly accompany cancer and may have an independent effect on higher-order function.

There are also concerns about whom to compare patients with, in terms of function: The patients' own levels of function prior to chemotherapy? Those of other cancer patients? Healthy control subjects' function levels? These are among the questions that should be settled for research to be most meaningful, he said.

Perhaps the most comprehensive analysis of chemotherapy and cognitive function is a metaanalysis of 30 studies of 29 populations comprising a total of 838 adult patients. The studies included three research designs that compared patients post treatment with control patients who had not undergone chemotherapy, with test scores obtained from normative controls, or with the patients' own baseline scores taken before starting treatment.

The cognitive domains tested included attention, verbal and visuospatial memory, visuospatial skill, executive function, psychomotor skill, and information processing speed.

For each domain, the investigators calculated a weighted Cohen's d score, which measures effect size. The scores ranged from 0 (no effect) to +2 (improvement in function) or -2 (deterioration of function), with a score greater than 8 in either direction considered a significant effect, Dr. Bonds noted.

The patients who underwent chemotherapy showed the greatest treatment effects in executive function and verbal memory when compared with the normative controls, with scores of -.93 and -.91, respectively. A significant effect on motor function was also seen (J. Int. Neuropsychol. Soc. 2003;9:967-82).

In other controlled research, conducted mostly on women with breast cancer, the rate of cognitive impairment associated with chemotherapy has ranged from 16% to 50% and has persisted for as long as 10 years. Combination chemotherapy with methotrexate, cyclophosphamide, and 5-fluorouracil has been most frequently associated with cognitive problems, although neurotoxicity has also been reported with other commonly used cancer drugs, Dr. Bonds said. (See table.)

On the other hand, anthracycline-based agents seem to be associated less frequently with neurotoxicity, he said.

Studies on possible neuroprotective agents are now under way. Until then, Dr. Bonds recommended a baseline cognitive assessment for chemotherapy candidates. He also suggested that doctors and patients consider whether chemotherapy is always the best option and that they include the potential for cognitive impairment and its subsequent impact on quality of life in any assessment of risks and benefits.

Patients who choose to proceed with chemotherapy should investigate coping strategies, such as avoidance of stressful situations, diminished workload, plenty of sleep, and keeping lists.

Physicians should treat these patients aggressively for anxiety and depression and offer them a program of psychological rehabilitation to assist with self-care.

Suspect Drugs

Chemotherapy Agents Associated With Neurotoxicity
Combination of methotrexate*, cyclophosphamide, and fluorouracil*
Vinca alkaloids
Cytarabine
Platinum analogues
Ifosfamide
Taxol
Taxotere
Fludarabine
Suramin

Agents Associated With Occasional Reports of Cognitive or Motor
Impairment
L-asparagine
Busulfan
Hexamethylmelamine
Procarbazine
Thiotepa

*Also associated with cognitive impairment individually.
Source: Dr. Bonds

BY NORRA MACREADY

Los Angeles Bureau