levoleucovorin and Cognition-Disorders

Chemotherapy-related cognitive impairment can occur in cancer survivors after treatment, especially those patients who have undergone chemotherapy for breast cancer. The frequency and to what extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. The present prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC compared with a control group who had not undergone chemotherapy.. Consecutive patients with localized stage II and III CRC completed neuropsychological assessments, self-reported cognitive complaint questionnaires, and depressive symptom evaluations before starting fluoropyrimidine-based adjuvant chemotherapy and after 12 months. Blood was collected for apolipoprotein E genotyping. Diffusion tensor imaging data were acquired from a subset of participants at both evaluation points.. From December 2012 to December 2014, 137 patients were approached and 85 were included. Of these 85 patients, 49 had undergone chemotherapy and 26 had not, in accordance with the standard recommendations for adjuvant therapy for CRC. The mean age was 62.5 ± 9.4 years, 60% were men, and the mean educational attainment was 7.6 ± 3.7 years. No difference was found in the global composite score (P = .38), attention (P = .84), or memory (P = .97) between the 2 groups during the follow-up period (mean ± standard deviation, 375 ± 29 days). However, a statistically significant difference was found for executive function after adjustment for age, sex, education, and depressive symptoms at baseline (β -1.80; 95% confidence interval, -3.50 to -0.11; P = .04), suggesting worse performance for the chemotherapy group. For the 32 patients who had undergone magnetic resonance imaging, tract-based spatial statistics did not show voxelwise significant differences in structural brain connectivity at baseline or during follow-up. Apolipoprotein E polymorphisms were not predictive of cognitive dysfunction.. Patients with CRC who received adjuvant 5-fluorouracil with or without oxaliplatin presented with a decline in executive function after 12 months compared with patients with localized disease who had not received chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemotherapy, Adjuvant; Cognition Disorders; Colorectal Neoplasms; Diffusion Tensor Imaging; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neuropsychological Tests; Oxaliplatin; Prognosis; Prospective Studies; Surveys and Questionnaires

Folate receptor alpha (FRα) autoantibodies have been associated with fetal abnormalities and cerebral folate deficiency-related developmental disorders. Over 70% of the children with autism spectrum disorders (ASD) are positive for these autoantibodies and high-dose folinic acid is beneficial in treating these children. Here we show that antibodies (Abs) to the rat FRα administered during gestation produce communication, learning and cognitive deficits in a rat model that can be prevented by folinic acid and dexamethasone. FRα Ab can trigger inflammation as well as block folate transport to the fetus and to the developing brain to produce the functional deficits. In humans, exposure to FRα autoantibodies during fetal development and infancy could contribute to brain dysfunction such as that seen in ASD and other developmental disorders. Identifying women positive for the autoantibody and treating them with high-dose folinic acid along with other interventions to lower the autoantibody titer are effective strategies that may be considered to reduce the risk of having a child with developmental deficits.

Topics: Animals; Antibodies; Autistic Disorder; Autoantibodies; Child; Cognition Disorders; Dexamethasone; Female; Folate Receptor 1; Folic Acid; Humans; Leucovorin; Male; Pregnancy; Rats; Rats, Long-Evans

To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS).. Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity.. Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%).. FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cognition; Cognition Disorders; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Immunosuppressive Agents; Infusions, Intravenous; Italy; Leucovorin; Maintenance Chemotherapy; Male; Organoplatinum Compounds; Psychometrics; Retrospective Studies; Stomach Neoplasms; Survival Rate; Time Factors; Treatment Outcome; Vitamin B Complex

Chemotherapy can induce cognitive impairment in cancer patients. The main goal of this longitudinal study was to determine the incidence, characteristics, and duration of cognitive dysfunction in patients treated with adjuvant chemotherapy for colon cancer.. We assessed cognitive function, quality of life, anxiety and depression, fatigue, and hemoglobin levels in colon cancer patients at three assessment points: pre-chemotherapy (n=81), post-chemotherapy (n=73), and after 6-month follow-up (n=54). All patients were treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) for 6 months.. Thirty patients (37%) had cognitive impairment in the pre-chemotherapy evaluation, mainly in processing speed and psychomotor executive function (Trail Making Test A and B). At the end of treatment, the main domain affected was the verbal memory, with an acute decline detected in 56% of patients. Fifty-four percent of the patients improved their dysfunction after 6 months of follow-up, whereas 18 (33%) of them showed worsening in at least one test. Cognitive impairment was most common in older patients and in those with less years of education. Quality of life, anxiety, depression, fatigue, and hemoglobin did not influence the results of the cognitive tests.. Adjuvant FOLFOX4 in patients with colon cancer can have a negative effect on verbal memory. This deterioration is usually mild and transient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cognition; Cognition Disorders; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Longitudinal Studies; Male; Memory; Middle Aged; Organoplatinum Compounds; Oxaliplatin

Chemotherapy improves the survival rate of stage III colon cancer patients. The combination of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) has emerged as the standard of care. This prospective study evaluates potential alterations in cognitive function in FOLFOX4-treated patients.. We evaluated 57 consecutive colorectal cancer patients who received adjuvant chemotherapy with FOLFOX4. Patients underwent a complete battery of neuropsychological tests at three different times: before (T0), at the end (T1), and 6 months after treatment (T2).. We have analyzed cognitive impairment (Mini Mental State Examination, MMSE), visuo-spatial memory (Clock Drawing Test, CDT, Rey Complex Figure, copy and recall), information processing speed (Trial Making Test-A, TMT-A, and Trial Making Test-B, TMT-B), verbal memory (Rey Auditory Verbal Learning Test, call and recall), emotional distress (Psychological Distress Inventory, PDI), anxiety (State and Trait Anxiety Inventory, STAI-Y1 and Y2), and depression (Beck Depression Inventory, BDI). Then we have calculated, for each test and for each interval of time, mean ± standard deviation for the mean. In a subsequent phase, we tested the significance of different results through the ANOVA analysis for repeated measures. In this case, we could not find any statistically significant modification in cognitive function, but we could notice an improvement in emotional performance, anxiety and depression a short time after chemotherapy administration.. We found no effect on cognitive function related to chemotherapy, the only little modification is about some emotional performance during chemotherapy. These findings may be explained by the central role of the psychological adaptation process, which occurs during the period from diagnosis to completion of treatment and is characterized by anxiety and adjustment depression. Our results seem to rule out any significant cognitive impairment due to adjuvant FOLFOX4 chemotherapy in colon cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cognition; Cognition Disorders; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neuropsychological Tests; Organoplatinum Compounds; Pilot Projects; Prospective Studies

To describe a patient with reversible posterior leukoencephalopathy syndrome following the administration of bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor.. Case report/literature review.. University hospital.. A 52-year-old man receiving chemotherapy for stage IV rectal carcinoma.. Clinical and radiographic evidence consistent with reversible posterior leukoencephalopathy syndrome was found following the administration of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy and bevacizumab.. Reversible posterior leukoencephalopathy syndrome following treatment with angiogenesis modulators can occur. In addition to raising clinical suspicion in appropriate patients, this report may yield clues to the pathophysiologic underpinnings of reversible posterior leukoencephalopathy syndrome.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Aphasia; Bevacizumab; Blindness, Cortical; Blood Vessels; Camptothecin; Carcinoma; Cognition Disorders; Colonic Neoplasms; Dementia, Vascular; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Occipital Lobe; Parietal Lobe; Vascular Endothelial Growth Factor A

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 +/- 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 +/- 15.69 and 84.83 +/- 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 +/- 15.46 and 88.30+/- 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity.

Topics: Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Brain; Child; Child, Preschool; Cognition Disorders; Cohort Studies; Cytarabine; Female; Hematinics; Humans; Hydrocortisone; Leucovorin; Male; Methotrexate; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Wechsler Scales

Infants diagnosed with acute lymphoblastic leukemia (ALL) are considered the patient subgroup at the highest risk for central nervous system (CNS) disease, both at presentation and as an isolated extramedullary relapse. In addition, they are highly vulnerable to adverse developmental sequelae from CNS-directed therapy.. Thirty patients younger than 12 months at diagnosis (12 males, 18 females) in first hematologic remission were evaluated after completion of ALL therapy (mean age = 62.1 months; standard deviation = 17.2 months; range = 38-102 months). CNS-directed treatment included very high dose infusions of methotrexate (MTX) and intrathecal cytarabine and MTX. Three patients had meningeal leukemia that required additional therapy. Children were administered the McCarthy Scales of Children's Abilities, and parents completed a sociodemographic questionnaire to obtain information about occupation and education.. Mean scores on all 6 cognitive and motor indices of the McCarthy Scales were in the average range (Verbal = 52.0; Perceptual = 53.6; Quantitative = 49.6; General Cognitive Index [GCI] = 102.1; Memory = 49.2; Motor = 51.0). Score distributions for each neurodevelopmental index were comparable to age-based population standards. One patient obtained a GCI that exceeded 2 standard deviations above the mean; none scored more than 2 standard deviations below. There was no report of developmental disabilities or neurologic disorders for any of the patients. Risk factors, including age at diagnosis, gender, additional CNS-directed treatment, and family socioeconomic status, were not associated with developmental outcome.. Test findings indicated a generally positive neurodevelopmental outcome for ALL patients diagnosed in infancy who were treated with very high dose MTX as CNS-directed therapy. Combined with the reduction in the isolated CNS relapse rate achieved by the Children's Cancer Group (CCG) clinical trial CCG-107, the results of this study represent a substantial improvement in neurodevelopmental outcome for very young patients compared with infants treated for ALL in the past.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Damage, Chronic; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Developmental Disabilities; Female; Follow-Up Studies; Humans; Infant; Injections, Spinal; Leucovorin; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Movement Disorders; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Psychomotor Performance; Remission Induction; Risk; Socioeconomic Factors; Survivors; Vincristine