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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.
References
Bernsen, H.J., Rijken, P.F., Peters, J.P., Bakker, J.H., Boerman, R.H., Wesseling, P., and van der Kogel, A.J. (1999) Suramin treatment of human glioma xenografts; effects on tumor vasculature and oxygenation status. J. Neurooncol. 44,129 -136.[CrossRef][Medline]
Butler, S.J., Kelly, E.C., McKenzie, F.R., Guild, S.B., Wakelam, M.J., and Milligan, G. (1988) Differential effects of suramin on the coupling of receptors to individual species of pertussis-toxin-sensitive guanine-nucleotide-binding proteins. Biochem. J. 251,201 -205.[Web of Science][Medline]
Coffey, R.J. Jr., Leof, E.B., Shipley, G.D., and Moses, H.L. (1987) Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J. Cell Physiol. 132,143 -148.[CrossRef][Web of Science][Medline]
Coomber, B.L. (1995) Suramin inhibits C6 glioma-induced angiogenesis in vitro. J. Cell Biochem. 58,199 -207.[CrossRef][Web of Science][Medline]
Coughlin, C., Scott, C., Langer, C., Coia, L., Curran, W., and
Rubin, P. (2000) Phase II, two-arm RTOG trial (94-11) of
bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy
(64.0 or 70.4 Gy) based on tumor volume (20 or >2 
20 cm, respectively)
in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma
multiforme patients. Int. J. Radiat. Oncol. Biol.
Phys. 48,1351
-1358.[CrossRef][Web of Science][Medline]
Cox, D.R. (1972) Regression models and life-tables (with discussion). J. R. Stat. Soc. B 34,187 -220.
Del Rowe, J., Scott, C., Werner-Wasik, M., Bahary, J.P., Curran,
W.J., Urtasun, R.C., and Fisher, B. (2000) Single-arm, open-label
phase II study of intravenously administered tirapazamine and radiation
therapy for glioblastoma multiforme. J. Clin. Oncol.
18,1254
-1259.
Eisenberger, M.A., Reyno, L.M., Jodrell, D.I., Sinibaldi, V.J.,
Tkaczuk, K.H., Sridhara, R., Zuhowski, E.G., Lowitt, M.H., Jacobs, S.C., and
Egorin, M.J. (1993) Suramin, an active drug for prostate cancer:
Interim observations in a phase I trial. J. Natl. Cancer
Inst. 85,611
-621 [erratum in J. Natl. Cancer Inst.
86, 639-640, 1994].
Galvani, A.P., Cristiani, C., Carpinelli, P., Landonio, A., and Bertolero, F. (1995) Suramin modulates cellular levels of hepatocyte growth factor receptor by inducing shedding of a soluble form. Biochem. Pharmacol. 50,959 -966.[CrossRef][Web of Science][Medline]
Grossman, S.A., Fisher, J.D., Piantadosi, S., and Brem, H. (1998) The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium: Organization, objectives and activities. Cancer Control 5,107 -114.[Web of Science][Medline]
Grossman, S.A., Phuphanich, S., Lesser, G., Rozental, J., Grochow,
L.B., Fisher, J., and Piantadosi, S. (2001) New Approaches to
Brain Tumor Therapy CNS Consortium. Toxicity, efficacy, and pharmacology of
suramin in adults with recurrent high-grade gliomas. J. Clin.
Oncol. 19,3260
-3266.
Grossman, S.A., O'Neill, A., Grunnet, M., Mehta, M., Pearlman,
J.L., Wagner, H., Gilbert, M., Newton, H.B., and Hellman, R.
(2003) Phase III study comparing three cycles of infusional
carmustine and cisplatin followed by radiation therapy with radiation therapy
and concurrent carmustine in patients with newly diagnosed supratentorial
glioblastoma multiforme: Eastern Cooperative Oncology Group trial 2394.
J. Clin. Oncol. 21,1485
-1491.
Hensey, C.E., Boscoboinik, D., and Azzi, A. (1989) Suramin, an anti-cancer drug, inhibits protein kinase C and induces differentiation in neuroblastoma cell clone NB2A. FEBS Lett. 258,156 -158.[CrossRef][Web of Science][Medline]
Hosang, M. (1985) Suramin binds to platelet-derived growth factor and inhibits its biological activity. J. Cell Biochem. 29,265 -273.[CrossRef][Web of Science][Medline]
Howard, S.P., Groch, K.M., Lindstrom, M.J., Messing, E.M., and Gould, M.N. (1995) Proliferation-independent growth factor modulation of the radiation sensitivity of human prostate cells. Radiat. Res. 143,229 -233.[CrossRef][Web of Science][Medline]
Huang, S.S., and Huang, J.S. (1988) Rapid turnover of
the platelet-derived growth factor receptor in sis-transformed cells and
reversal by suramin. Implications for the mechanism of autocrine
transformation. J. Biol. Chem.
263,12608
-12618.
Kalbfleisch, J.D., and Prentice, R.L. (1980) The Statistical Analysis of Failure Time Data. New York: John Wiley & Sons, pp. 16-19.
Kaplan, E.L., and Meier, P. (1958) Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53,457 -481.[CrossRef][Web of Science]
Langer, C.J., Ruffer, J., Rhodes, H., Paulus, R., Murray, K., Mousas, B., and Curran, W. (2001) Phase II Radiation Therapy Oncology Group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 51,113 -119.
LaRocca, R.V., Cooper, M.R., Uhrich, M., Danesi, R., Walther, M.M., Linehan, W.M., and Myers, C.E. (1991) Use of suramin in treatment of prostatic carcinoma refractory to conventional hormonal manipulation. Urol. Clin. North Am. 18,123 -129.[Web of Science][Medline]
Moscatelli, D., and Quarto, N. (1989) Transformation
of NIH 3T3 cells with basic fibroblast growth factor or the hst/K-fgf oncogene
causes down-regulation of the fibroblast growth factor receptor: Reversal of
morphological transformation and restoration of receptor number by suramin.
J. Cell Biol. 109,2519
-2527.
Myers, C., Cooper, M., Stein, C., LaRocca, R., Walther, M.M., Weiss, G., Choyke, P., Dawson, N., Steinberg, S., Uhrich, M.M., Cassidy, J., Kohler, D.R., Trepel, J., and Linehan, W.M. (1992) Suramin: A novel growth factor antagonist with activity in hormone-refractory metastatic prostate cancer. J. Clin. Oncol. 10,881 -889.[Abstract]
NCI. National Cancer Institute (1999) Common Toxicity Criteria version 2.0. Available at https://webapps.ctep.nci.nih.gov/ctcv2/plsql/ctc000w$.startup.
Olson, J.J., Polk, D.M., and Reisner, A. (1994) The efficacy and distribution of suramin in the treatment of the 9L gliosarcoma. Neurosurgery 34,297 -308.[Web of Science][Medline]
Palayoor, S.T., Bump, E.A., Teicher, B.A., and Coleman, C.N. (1997) Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin. Radiat. Res. 148,105 -114.[Web of Science][Medline]
Reyno, L.M., Egorin, M.J., Eisenberger, M.A., Sinibaldi, V.J.,
Zuhowski, E.G., and Sridhara, R. (1995) Development and
validation of a pharmacokinetically based fixed dosing scheme for suramin.
J. Clin. Oncol. 13,2187
-2195.
Small, E.J., Meyer, M., Marshall, M.E., Reyno, L.M., Meyers, F.J.,
Natale, R.B., Lenehan, P.F., Chen, L., Slichenmyer, W.J., and Eisenberger, M.
(2000) Suramin therapy for patients with symptomatic
hormone-refractory prostate cancer: Results of a randomized phase III trial
comparing suramin plus hydrocortisone to placebo plus hydrocortisone.
J. Clin. Oncol. 18,1440
-1450.
Takano, S., Gately, S., Engelhard, H., Tsanaclis, A.M., and Brem, S. (1994) Suramin inhibits glioma cell proliferation in vitro and in the brain. J. Neurooncol. 21,189 -201.[CrossRef][Medline]
Teicher, B.A., Dupuis, N.P., Robinson, M.F., Emi, Y., and Goff, D.A. (1995) Antiangiogenic treatment (TNP-470/minocycline) increases tissue levels of anticancer drugs in mice bearing Lewis lung carcinoma. Oncol. Res. 7, 237-243.[Web of Science][Medline]
Teicher, B.A., Holden, S.A., Ara, G., Korbut, T., and Menon, K. (1996) Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma. Cancer Chemother. Pharmacol. 38,169 -177.[CrossRef][Web of Science][Medline]
Waltenberger, J., Mayr, U., Frank, H., and Hombach, V. (1996) Suramin is a potent inhibitor of vascular endothelial growth factor. A contribution to the molecular basis of its antiangiogenic action. J. Mol. Cell. Cardiol. 28,1523 -1529.[CrossRef][Web of Science][Medline]
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