motexafin-gadolinium and Cognition-Disorders

Increased life expectancy in patients with brain tumours has led to a greater risk of cognitive deficits, particularly during disease-free periods. Here, we review the empirical studies that have been done to treat or to prevent cognitive impairment in patients with brain tumours. Both pharmacological interventions and cognitive rehabilitation programmes have been used. Although both types of study have reported some successes, these are often difficult to interpret owing to limitations in the methods used. Most of the studies reviewed did not use a randomised group design to control for possible confounding factors such as placebo and practice effects. Investigations of newer, targeted therapies have reported delays in cognitive deterioration, but these need to be confirmed in future studies. Neuroprotection represents another potentially promising, novel approach to prevention of cognitive impairment in this vulnerable population of patients. Finally, we describe studies in patients with cancers outside the CNS, to highlight further possibilities for the prevention and treatment of cognitive deficits.

Topics: Brain; Brain Neoplasms; Central Nervous System Stimulants; Clinical Trials as Topic; Cognition Disorders; Cognitive Behavioral Therapy; Humans; Metalloporphyrins; Nootropic Agents; Radiotherapy; Treatment Outcome

To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer.. In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received.. Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed.. In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.

Topics: Aged; Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Female; Humans; Lung Neoplasms; Metalloporphyrins; Middle Aged; Proportional Hazards Models

To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).. Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed.. Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048).. Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.

Topics: Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Breast Neoplasms; Cognition Disorders; Cranial Irradiation; Disease Progression; Female; Humans; Lung Neoplasms; Male; Memory Disorders; Metalloporphyrins; Middle Aged; Motor Skills; Psychometrics; Survival Analysis; Treatment Outcome