[5][6] The clinical relevance of PCCI is significant, considering the increasing number of long-term cancer survivors in the population, many of whom may have been treated with aggressive dosing of chemotherapeutic agents, or with chemotherapy as an adjuvant to other forms of treatment.
[8] The systems of the body most affected by chemotherapy drugs include visual and semantic memory, attention and motor coordination and executive functioning.
[9][10] These effects can impair a chemotherapy patient's ability to understand and make decisions regarding treatment, perform in school or employment and can reduce quality of life.
Often, survivors think their lives will return to normal when the cancer is gone, only to find that the lingering effects of post-chemotherapy cognitive impairment impede their efforts.
[7] Two major theories have been advanced:[4] the direct effect of chemotherapy drugs on the brain, and the role of hormones in nervous system health.
Menopause, the biological impact of a surgical procedure with anesthesia, medications prescribed in addition to the chemotherapy, genetic predisposition, hormone therapy, emotional states (including anxiety, depression and fatigue), comorbid conditions and paraneoplastic syndrome may all co-occur and act as confounding factors in the study or experience of PCCI.
[8] Chemotherapy drugs thalidomide, the epothilones such as ixabepilone, the vinca alkaloids vincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin often cause chemotherapy-induced peripheral neuropathy, a progressive and enduring tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.
[15][16][17] In most cases there is no known way of reducing the effects of chemotherapeutic agents related to taxanes, thalidomide and platinum-based compounds (oxaliplatin is a notable exception to the latter category—though it does cause PCCI its effects can be buffered by infusion of calcium and thought related to PCCI include the ability of the nerves to repair themselves, the ability of cells to excrete compounds, permeability of the blood–brain barrier, damage done to DNA including shortening of telomeres and cellular oxidative stress.
Due to the critical role the hippocampus plays in memory, it has been the focus of various studies involving post-chemotherapy cognitive impairment.
[26] Methotrexate, an agent widely used in the chemotherapy treatment of breast cancer, has also displayed a long-lasting dose dependent decrease in hippocampal cell proliferation in the rat following a single intravenous injection of the drug.
[27] This evidence suggests that chemotherapy agent toxicity to cells in the hippocampus may be partially responsible for the memory declines experienced by some patients.
[9] While these physical and mental forms of management for PCCI symptoms show subjective improvements, they are less supported in regards to objective assessment and still require further testing.
Modafinil is a wakefulness-promoting agent that can improve alertness and concentration, and studies have shown it to be effective at least among women treated for breast cancer.
[13] These large discrepancies cause confusion as to how common PCCI is and which cognitive functions are actually being impaired, which can have harmful impacts on the future of research for treatments and implementation of interventions.
[36] Research on PCCI is limited, and studies on the subject have often been conflicting in results, in part due to differing means of assessing and defining the phenomenon, which makes comparison and synthesis difficult.
In 2005, Dr. Masatoshi Inagaki used magnetic resonance imaging (MRI) to measure differences in brain volume between breast cancer patients exposed to chemotherapy and subjects unexposed.
However, in the three-year study, both groups of breast cancer survivors were observed to have similar gray and white matter volumes.
The authors of this study declare that commonly chemotherapy patients will self-report cognitive complaints, although they perform within normal limits on neuropsychological tasks.
[38][39][40][41][42] The symptoms of PCCI were recognized by researchers in the 1980s, who typically described it as mild cognitive impairment subsequent to successful cancer treatment.