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A phase II study of temozolomide plus
pegylated interferon alfa-2b for recurrent anaplastic glioma and
glioblastoma multiforme
M. D. Groves, V.
Puduvalli, M. R. Gilbert, C. A. Conrad,
S. Hsu, H. Colman, K. Hess, V.
A. Levin and W. K. A. Yung
Univ of Texas MD Anderson Cancer
Ctr, Houston, TX
Background. Based on
prior studies suggesting promise of interferon alfa-2b and
temozolomide (TMZ) in relapsed malignant glioma patients,
we are testing this combination with a long acting (pegylated)
form of interferon alfa-2b (PIFN) prolonging drug exposure
and attempting to increase anti-tumor activity.
Methods. We
are conducting a prospective phase II trial of TMZ plus PIFN in
adult patients with recurrent anaplastic glioma (AG) and glioblastoma
multiforme (GBM), after surgery and radiotherapy (and
chemotherapy in some cases), with adequate organ function and
KPS ≥60.
TMZ is administered at 150–200 mg/m2/day on days 1–5 of
each 28-day cycle, and PIFN is administered subcutaneously
at 0.5 microgram/kg every week.
Two 28-day cycles equals one course.
Patients are re-evaluated with neurological examinations
and neuro-imaging every 56 days.
The study is powered to detect an improvement of the
historic 6-month progression-free survival (PFS) from 15%
to 30% for GBM patients and from 20% to 40% for AG
patients.
Results. Thirty-five
patients have enrolled, 9 with recurrent AG and 26 with
recurrent GBM, 15 women, 20 men, median age is 55 years
(range 20–67), median KPS is 90 (range 70–100).
Grade 3 or 4 toxicity occurred in 29 patients, 10 patients
required dose reduction, 2 of TMZ, 8 of both drugs.
Common grade 3 or 4 toxicities included leukopenia or
thrombocytopenia in 15 patients.
Best responses were no change in 23/34 (68%).
Kaplan-Meier estimates revealed 38% of GBM patients and 44%
of AG patients alive and free from progression at 6 months
after enrollment.
Conclusions. Preliminary
results of TMZ combined with PIFN in recurrent AG and GBM,
despite a lack of any objective radiologic responses,
produced a 6 month PFS in both subgroups that surpasses the
target 6 month PFS.
This improved outcome appears to come at a price of
increased toxicity.
This combination may warrant further investigation in a randomized
trial or with other anti-neoplastic agents.
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