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Phase II trial of thalidomide (TD),
tamoxifen (TX), and temozolomide (T) for patients with advanced
malignant gliomas (MG)
T. Ahmed, B.
Chen, G. Rabbani, M. N. Wallam and D.
Benzil
New York Medcl Coll, Valhalla, NY
Background. Patients with
MG have a poor survival despite surgery, radiation therapy
(RT).
Chemotherapy (CTX) is often used but the overall impact on
survival is poor.
Methods. We studied the
combination of TD, TX and T in a phase II trial for patients with
MG.
Standard response criteria and NCI toxicity criteria were
used.
We also assessed quality-of-life (QoL).
Eligibility criteria included histologic confirmation of
Glioblastoma (GBM) or Anaplastic astrocytoma (AA), no chemo
or RT for 3 weeks and ECOG PS of ≤ 2.
20 patients entered the trial: 8 were female; median age 51
years (r 24–84); 17 had GBM and 3 had AA.
9 patients had prior RT and 5 prior CTX.
28-day treatment cycles consisted of daily TD 100 mg PO and
TX 100 mg PO for the full duration of each cycle and T 75
mg/m2 PO) for the first 21 days of each cycle.
Treatment continued until disease progression.
Primary outcomes measures were patient survival, response, toxicity
and changes in QoL.
Results. 6 patients
discontinued therapy prior to response evaluation.
9 of 14 patients had disease stabilization and response
(64%, 95% CI, 39%–89%), lasting 8–135 weeks (median 12
weeks) documented by MRI scan.
No CR was seen.
One patient remained progression free for 2 years.
By Kaplan Meier analysis, mean survival was 75 ± 18 weeks
(95% CI, 41–110 weeks) with a median time to progression
of 47 weeks (95% CI, 15–79 weeks).
One patient had a sustained decrease in WBC and T was
held.
Mean WBC was 9.4 x10e3/ul, which fell to a mean of 5.58 x
10e3/ul.
Hgb and platelets were not significantly affected.
4 patients developed deep vein thrombosis (DVT): subsequent
patients were given prophylactic warfarin.
2 patients had pulmonary embolism.
No other grade 3 or 4 toxicities were noted.
Changes in QoL scores during treatment did not significantly correlate
with disease progression.
Conclusions. Outpatient
therapy with temozolomide, thalidomide, and tamoxifen is well
tolerated and results in stabilization/response in 64% of
patients.
Prophylaxis with warfarin may prevent DVT in patients on tamoxifen.
The overall impact on survival will require further study.
Supported by the ZA Arlin
Cancer Research Institute, Schering-Plough Corp. and
Celgene Corp.
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