Phase II study of concurrent continuous Temozolomide (TMZ) and Tamoxifen (TMX) for recurrent malignant astrocytic gliomas.
OBJECTIVE
The aim of this study was to assess the frequency of response and toxicity in adults with recurrent anaplastic astrocytoma (AA) or glioblastoma multiforme (GM) treated with concurrent continuous TMZ and TMX.


METHODS
In addition to histology, eligibility included age > 18 years, Karnovsky score > or = 60, normal laboratory parameters, no radiotherapy (RT) for 4 weeks, measurable disease and normal EKG. The chief exclusions were: previous TMZ, TMX or dacarbazine (DTIC); nitrosourea within 6 weeks; history of deep venous thrombosis or pulmonary emboli. All patients (pts) had received prior RT. TMZ was given at 75 mg/M2/day for 6 weeks, repeated every 10 weeks, maximum 5 cycles. Four pts received 60 mg/M2/day for 6 weeks due to extensive prior chemotherapy exposure. TMX was started at 40 mg twice daily (b.i.d.) for 1 week and then was increased in three successive weeks to 60, then 80, then 100 mg b.i.d. Response was assessed before every cycle with MRI +/- gadolinium (Gd).


RESULTS
Sixteen pts enrolled: GM 10, AA 6; female 6, male 10; median age 48 (21-58); prior chemotherapy 7. There was one partial response and one stable disease. Eleven pts progressed by the end of cycle 1; three pts failed due to toxicity before completing cycle 1. Median time to treatment failure was 10 weeks. The main toxicities were: transaminitis, pancytopenia, 1st division herpes zoster, deep vein thrombosis and fatigue. The study was closed due to the low response rate and frequency of toxicity.
Spence
Alexander M
AM
Departments of Neurology, University of Washington School of Medicine, Seattle, WA 98195, USA. aspence@u.washington.edu
Peterson
Richard A
RA
Scharnhorst
Jeffrey D
JD
Silbergeld
Daniel L
DL
Rostomily
Robert C
RC
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D000077204:Temozolomide; D016896:Treatment Outcome
D013629:Tamoxifen; D003606:Dacarbazine; D000077204:Temozolomide