Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.
OBJECTIVE
This phase III randomized trial evaluated survival as well as 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 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated.


RESULTS
Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients.


CONCLUSIONS
The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.
Mehta
Minesh P
MP
University of Wisconsin-Madison, Department Human Oncology Radiation Oncology, 53792, USA. mehta@mail.humonc.wisc.edu
Rodrigus
Patrick
P
Terhaard
C H J
CH
Rao
Aroor
A
Suh
John
J
Roa
Wilson
W
Souhami
Luis
L
Bezjak
Andrea
A
Leibenhaut
Mark
M
Komaki
Ritsuko
R
Schultz
Christopher
C
Timmerman
Robert
R
Curran
Walter
W
Smith
Jennifer
J
Phan
See-Chun
SC
Miller
Richard A
RA
Renschler
Markus F
MF
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary*; D003071:Cognition; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D013534:Survival; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium