Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial.
OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Meyers
Christina A
CA
Department of Neuro-Oncology, Unit 431, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. cameyers@mdanderson.org
Smith
Jennifer A
JA
Bezjak
Andrea
A
Mehta
Minesh P
MP
Liebmann
James
J
Illidge
Tim
T
Kunkler
Ian
I
Caudrelier
Jean-Michel
JM
Eisenberg
Peter D
PD
Meerwaldt
Jacobus
J
Siemers
Ross
R
Carrie
Christian
C
Gaspar
Laurie E
LE
Curran
Walter
W
Phan
See-Chun
SC
Miller
Richard A
RA
Renschler
Markus F
MF
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D016371:Cranial Irradiation / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009048:Motor Skills; D011594:Psychometrics; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium