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Clinical Therapy Trials—Drug |
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 (J.J.L., S.A.G., K.A.C); Department of Hematology and Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157 (G.J.L.); Brain Tumor Center, Massachusetts General Hospital, Boston, MA 02114 (F.H.H.); and Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (M.R.G.); USA
2 Address correspondence to John Laterra, c/o The NABTT CNS Consortium, G87 Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231, USA (jfisher{at}jhmi.edu).
Abstract
Suramin is a polysulfonated naphthylurea that inhibits the function of
growth factors and growth factor receptors implicated in glioma progression,
angiogenesis, and radioresistance. The safety and benefits of combining
inhibitors of angiogenesis and growth factors with cytotoxic therapies in
patients with neoplasms of the central nervous system remain unclear. The
objectives of this phase 2 study were to determine the safety of administering
suramin with standard cranial radiotherapy (RT) and to estimate survival using
this approach in patients with newly diagnosed glioblastoma multiforme (GBM).
Fifty-five patients with newly diagnosed GBM (Karnofsky performance status
60) were enrolled in this multicenter phase 2 study. Patients received
suramin by a conventional intermittent fixed-dosing regimen for 1 week prior
to and during cranial RT (60 Gy in 30 fractions, weeks 2-7). Patients with
stable or responsive disease at week 18 received an additional 4 weeks of
suramin (weeks 19-22). The median survival for suramin-treated patients was
11.6 months, with 1-year and 18-month survival rates of 49% (95% confidence
interval [CI], 36%-62%) and 18% (95% CI, 8%-28%), respectively. Overall, 55%
of the patients (30/55) had greater than grade 2 toxicity at least possibly
related to suramin therapy. Two patients died of possibly related neurologic
events (i.e., stroke, elevated intracranial pressure). Otherwise, toxicities
were generally transient and self-limited. Administration of suramin using an
intermittent fixed-dosing regimen during cranial RT was generally well
tolerated. However, overall survival is not significantly improved when
compared with the New Approaches to Brain Tumor Therapy GBM database or other
comparable patient populations.
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