<b>ChemoBrain Medical Journal Abstracts</b>
[Edited abstracts]

Breast Cancer Res Treat 2001 Nov;64(2):165-76
<b>Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen.</b>
Paganini-Hill A, Clark LJ. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA. annlia@juno.com

"... Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function."

"... Information from 1,163 women aged 57-75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users ... This was especially true for current users ... Current users also had a significantly lower mean complexity score ... on the narrative writing task. No differences were seen between past users and non-users...: <b>Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment.</b>" 
&&url PMID: 11194452


J Clin Oncol 2000 Jul;18(14):2695-701
<b>Cognitive function in breast cancer patients receiving adjuvant chemotherapy.</b>
Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF. Department of Medical Oncology and Hematology, Department of Biostatistics, Department of Psychosocial Oncology, Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.

"Breast cancer patients receiving chemotherapy have complained of difficulties in their ability to remember, think, and concentrate. This study assessed whether there are differences in cognitive function between breast cancer patients treated with standard-dose adjuvant chemotherapy compared with healthy controls."

"Cognitive differences were observed in breast cancer patients receiving adjuvant chemotherapy compared with healthy controls. These differences did not seem to be caused by significant differences in mood disturbance between the two groups. If confirmed, these results have substantial implications for informed consent, counseling, and psychosocial support of patients receiving adjuvant chemotherapy for breast cancer." 
&&url PMID: 10894868


Cancer 1999 Feb 1;85(3):640-50
<b>Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma.</b>
Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF. Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam.

"<b>A number of patients who have undergone adjuvant (CMF) chemotherapy for operative primary breast carcinoma have reported impaired cognitive function, sometimes even years after completion of therapy.</b> The possible role of cytostatic treatment as a causative factor has scarcely been investigated. The objective of the current study was to examine the late effects on neuropsychologic functioning of CMF adjuvant chemotherapy given to patients with breast carcinoma. <b>...Breast carcinoma patients treated with adjuvant CMF chemotherapy have a significantly higher risk of late cognitive impairment than breast carcinoma patients not treated with chemotherapy (OR 6.4). This cognitive impairment is unaffected by anxiety, depression, fatigue, and time since treatment, and not related to the self-reported complaints of cognitive dysfunction.</b>" 
&&url PMID: 10091737 


J Clin Oncol 1999 Feb;17(2):706-18
<b>Health-related quality of life 1 year after allogeneic or autologous stem-cell transplantation: a prospective study.</b>
Hjermstad MJ, Evensen SA, Kvaloy SO, Fayers PM, Kaasa S. Norwegian Cancer Society, Department of Oncology, Norwegian Radium Hospital, Oslo. mlhjerm@online.no

" To evaluate health-related quality of life (HRQOL) in adults treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem-cell transplantation 1 year after transplantation, using data from concurrent lymphoma patients receiving combination chemotherapy (CT) as a reference. ...: Forty-one leukemia patients (SCT group), 51 lymphoma patients (ASCT group), and 85 CT patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline and after 1 year."

"The SCT group ... had better functioning scores and less symptomatology at baseline compared with the ASCT ...and CT ... groups. Statistically significant differences of 10 or more points on the 0 to 100 scales were found for 10 of 15 scales and items (P< or =.01) between the SCT and ASCT groups. Global quality of life (79 v 58, P<.0001), role function (83 v 65, P = .001), sleep disturbances (6 v 28, P<.0001), and fatigue (25 v 44, P = .0001) deviated most. The differences were 10 or more points for seven of 15 scales and items comparing the SCT and CT groups, with sleep disturbances (6 v 35, P<.0001) and pain (11 v 29, P<.01) deviating most. Differences across groups were smaller after 1 year; <b>cognitive function was the only scale with a statistically significant difference (ASCT 80 v CT 89; P = .002)</b>. Patterns of change in HRQOL scores were different between groups during follow-up. A great improvement was found in the ASCT group (P<.01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group. CONCLUSION: Prospective studies with extended follow-up periods are necessary to separate a slow recovery process from more permanently reduced HRQOL after transplantation and to examine the late side effects from previous treatment." 
&&url PMID: 10080617


Clin Cancer Res 1997 Mar;3(3):419-22
<b>Neurotoxicity of CI-980, a novel mitotic inhibitor.</b>
Meyers CA, Kudelka AP, Conrad CA, Gelke CK, Grove W, Pazdur R. Departments of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, and Parke-Davis Pharmaceutical Research.

"CI-980 is a chemotherapeutic agent currently in Phase II trials that arrests cellular division .... It is structurally and functionally similar to colchicine, a potent nonreversible neurotoxin, and is able to cross the blood-brain barrier. In Phase I studies, neurotoxicity was noted. The neurotoxicity of CI-980 was prospectively evaluated in two Phase II studies by neurological evaluation, quantitative sensory testing, and neuropsychological assessment of cognitive functioning. The results revealed a significant but reversible decline in recent memory functioning after each course of CI-980, with no effect on overall mental status or neurological function. Sixty-seven percent of patients performed in the impaired range on the memory test after their first infusion, whereas only one exhibited a decline on a brief cognitive screen. The results are consistent with the known effects of colchicine on the brain. Colchicine selectively blocks choline acetyltransferase in the hippocampus and basal forebrain, the area of the brain responsible for memory consolidation. Although the effect of CI-980 was reversible at the dose and schedule used, this study suggests that careful monitoring of cognitive function in patients receiving this agent should be performed if dose or schedule parameters are changed. <b>In addition, this study demonstrates the feasibility of incorporating neuropsychological assessment in clinical trials of new anticancer agents having potential neurotoxic side effects.</b>" 
&&url PMID: 9815700


J Clin Oncol 1998 Jul;16(7):2522-7
<b>Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.</b>
Meyers CA, Weitzner MA, Valentine AD, Levin VA. Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. cmeyers@audumla.mdacc.tmc.edu

"<b>Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy.</b> We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. ... Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. ...<b>This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.</b>"  
&&url PMID: 667273


J Natl Cancer Inst 1998 Feb 4;90(3):210-8 Comment in: J Natl Cancer Inst. 1998 Feb 4;90(3):182-3
<b>Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy.</b>
van Dam FS, Schagen SB, Muller MJ, Boogerd W, vd Wall E, Droogleever Fortuyn ME, Rodenhuis S. Department of Psychosocial Research and Epidemiology,The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam.

BACKGROUND: <b>Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers, the long-term toxic effects of such therapy are a concern. Cognitive deficits (e.g., problems with memory and concentration) are not uncommon after chemotherapy, but they have not been documented systematically.</b> In this study, we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were randomly assigned to receive either high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, and we investigated whether high-dose chemotherapy impaired cognitive functioning more than standard-dose chemotherapy."

"<b>The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen, 36 patients treated with standard-dose chemotherapy plus tamoxifen, and 34 control patients.</b> For all patients, the average time since the completion of last nonhormonal therapy was 2 years. <b>Cognitive impairment was found in 32% of the patients treated with high-dose chemotherapy, in 17% of the patients treated with standard-dose chemotherapy, and in 9% of the control patients.</b> In comparison with the control patients, patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment ... in comparison with the patients who received standard-dose chemotherapy, this risk of impairment was 3.5-times higher ..."

"<b>High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.</b>" 
&&url PMID: 9462678 

