|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Clinical Therapy Trials—Drugs |
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany (M.W.); Guilford Pharmaceuticals, Baltimore, MD 21224, USA (D.C.H., E.B.); Aventis Pharma France, Paris, France (P.D., R.O.); Walton Centre for Neurology and Neurosurgery, Liverpool, UK (P.C.W.); Department of Neurosurgery, Western General Hospital, Edinburgh, Scotland (I.R.W.); Department of Neurosurgery, Topeliuksenkatu 5, Helsinki, Finland (J.J.); Department of Neurosurgery, Chaim Sheba Medical Center, Tel-Aviv, Israel (Z.R.)
3 Address correspondence and reprint requests to Manfred Westphal, Department of Neurosurgery, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (Westphal{at}uke.uni-hamburg.de).
Abstract
A previous placebo-controlled trial has shown that biodegradable 1,3-bis
(2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival
in patients with recurrent glioblastoma multiforme. A previously completed
phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed
malignant glioma also demonstrated a survival benefit in those patients
treated with BCNU wafers. Because of the small number of patients in that
trial, a larger phase 3 trial was performed to confirm these results. Two
hundred forty patients were randomized to receive either BCNU or placebo
wafers at the time of primary surgical resection; both groups were treated
with external beam radiation postoperatively. The two groups were similar for
age, sex, Karnofsky performance status (KPS), and tumor histology. Median
survival in the intent-to-treat group was 13.9 months for the BCNU
wafer-treated group and 11.6 months for the placebo-treated group (log-rank
P-value stratified by country = 0.03), with a 29% reduction in the
risk of death in the treatment group. When adjusted for factors affecting
survival, the treatment effect remained positive with a risk reduction of 28%
(P = 0.03). Time to decline in KPS and in 10/11 neuroperformance
measures was statistically significantly prolonged in the BCNU wafer-treated
group (P 
0.05). Adverse events were comparable for the 2 groups,
except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the
placebo-treated group) and intracranial hypertension (9.1% in the BCNU
wafer-treated group vs. 1.7% in the placebo group). This study confirms that
local chemotherapy with BCNU wafers is well tolerated and offers a survival
benefit to patients with newly diagnosed malignant glioma.
References
Andrews, D.W., Das, R., Kim, S., Zhang, J., and Curtis, M. (1997) Tech netium-MIBI as a glioma imaging agent for the assessment of multi-drug resistance. Neurosurgery 40,1323 -1334.[CrossRef][Web of Science][Medline]
Bigner, D.D., Brown, M., Coleman, R.E., Friedman, A.H., Friedman, H.S., McLendon, R.E., Bigner, S.H., Zhao, X.G., Wikstrand, C.J., Pegram, C.N., Kerby, T., and Zalutsky, M.R. (1995) Phase 1 studies of treatment of malig nant gliomas and neoplastic meningitis with 131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin proteoglycan sulfate Mel-14 F(ab')2—A preliminary report. J. Neurooncol. 24,109 -122.[CrossRef][Medline]
Brada, M., and Yung, W.K.A. (2000) Clinical trial end points in malignant glioma: Need for effective trial design strategy. Semin. Oncol. 27 (Suppl. 6), 11-19.
Brem, H., Tamargo, R.J., Olivi, A., Pinn, M., Weingart, J.D., Wharam, M., and Epstein, J.I. (1994) Biodegradable polymers for controlled delivery of chemotherapy with and without radiation therapy in the monkey brain. J. Neurosurg. 80,283 -290.[Web of Science][Medline]
Brem, H., Piantadosi, S., Burger, P.C., Walker, M., Selker, R., Vick, N.A., Black, K., Sisti, M., Brem, S., Mohr, G., Morawetz, R., and Schold, S.C. (1995) Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345,1008 -1012.[CrossRef][Web of Science][Medline]
Cairncross, J.G., Macdonald, D.R., and Ramsay, D.A. (1992) Aggressive oligodendroglioma: A chemosensitive tumor. Neurosurgery 31,78 -82.[Web of Science][Medline]
Chang, S.M., and Prados, M.D. (1995) Chemotherapy for gliomas. Curr. Opinion Oncol. 7, 207-213.[Medline]
Cristante, L., Siepmann, G., Westphal, M., Hagel, C., and Hermann, H.D. (1992) Superselective application of cis-platinum in recurrent human glioblastoma. Reg. Cancer Treat. 4, 188-194.
Culver, K.W., Ram, Z., Wallbridge, S., Ishii, H., Oldfield, E.H.,
and Blaese, R.M. (1992) In vivo gene transfer with retroviral
vector-producer cells for treatment of experimental brain tumors.
Science 256,1550
-1552.
Fine, H.A., Dear, K.B.G., Loeffler, J.S., Black, P.M., and Canellos, G.P. (1993) Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant glioma in adults. Cancer 71,2585 -2597.[CrossRef][Web of Science][Medline]
Fontana, A., Constam, D.B., Frei, K., Malipiero, U., and Pfister, H.W. (1992) Modulation of the immune response by transforming growth factor ß. Int. Arch. Allerg. Immunol. 99, 1-7.[CrossRef][Web of Science][Medline]
Giese, A., and Westphal, M. (1996) Glioma invasion in the central nervous system. Neurosurgery 39,235 -252.[CrossRef][Web of Science][Medline]
Hildebrand, J., DeWitte, O., Dietrich, P.Y., and de Tribolet, N. (1997) Man agement of malignant brain tumors. Eur. Neurol. 38,238 -253.[Web of Science][Medline]
Hochberg, F., and Pruitt, A. (1980) Assumptions in the
radiotherapy of glioblastoma. Neurology
30,907
-911.
Jachimczak, P., Bogdahn, U., Schneider, J., Behl, C., Meixensberger, J., Apfel, R., Dorries, R., Schlingensiepen, K.H., and Brysch, W. (1993) The effect of transforming growth factor-ß 2–specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malig nant glioma. J. Neurosurg. 78,944 -951.[CrossRef][Web of Science][Medline]
Kleihues, P., and Cavenee, W.K. (2000) Pathology and Genetics of Tumours of the Nervous System. World Health Organization Classification of Tumours. Lyon: IARC Press.
Köppen, J.A., Herrmann, H.D., Giese, A., Franz, H.R., Raschdorff, C., von Koschitzky, H., and Westphal, M. (1991) Lymphokine-activated killer cells, interleukin-2 and tumor necrosis factor a in malignant glioma: Clin ical and laboratory findings. Reg. Cancer Treat. 3,338 -344.
Kramm, C.M., Sena-Esteves, M., Barnett, F.H., Rainov, N.G., Schuback, D.E., Yu, J.S., Pechan, P.A., Paulus, W., Chiocca, E.A., and Breakefield, X.O. (1995) Gene therapy for brain tumors. Brain Pathol. 5,345 -381.[Web of Science][Medline]
Laske, D.W., Youle, R.J., and Oldfield, E.H. (1997) Tumor regression with regional distribution of the targeted toxin TF-CRM 107 in patients with malignant brain tumors. Nat. Med. 3,1362 -1368.[CrossRef][Web of Science][Medline]
Lesser, G.J., and Grossman, S. (1994) The chemotherapy of high-grade astrocytomas. Semin. Oncol. 21,220 -235.[Web of Science][Medline]
Levin, V.A., Leibel, S.A., and Gutin, P.H. (1997) Neoplasms of the central nervous system. In: De Vita, V.T., Jr., Hellman, S., and Rosenberg, S.A. (Eds.), Cancer: Principles & Practice of Oncology, 5th ed., Vol. 2. Philadelphia: Lippincott-Raven Publishers, pp.2022 -2082.
Lieberman, D.M., Laske, D.W., Morrison, P.F., Bankiewicz, K.S., and Oldfield, E.H. (1995) Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J. Neurosurg. 82,1021 -1029.[Web of Science][Medline]
Martuza, R.L. (1997) Act locally, think globally. Nat. Med. 3,1323 .[CrossRef][Web of Science][Medline]
Merchant, R.E., Ellison, M.D., and Young, H.F. (1990) Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations. J. Neurooncol. 8, 173-188.[Medline]
Merchant, R.E., Baldwin, N.G., Rice, C.D., and Bear, H.D. (1997) Adoptive immunotherapy of malignant glioma using tumor-sensitized T lympho cytes. Neurol. Res. 19,145 -152.[Web of Science][Medline]
Mesnil, M., Piccoli, C., Tiraby, G., Willecke, K., and Yamasaki, H.
(1996) Bystander killing of cancer cells by herpes simplex virus
thymidine kinase gene is mediated by connexins. Proc. Natl. Acad.
Sci. USA 93,1831
-1835.
Prados, M.D., and Levin, V. (2000) Biology and treatment of malignant glioma. Semin. Oncol. 27 (Suppl. 6),1 -10.
Rainov, N.G., on behalf of the FL1328 International Study Group (2000) A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum. Gene Ther. 11,2389 -2401.[CrossRef][Web of Science][Medline]
Ram, Z., Culver, K.W., Oshiro, E.M., Viola, J.J., DeVroom, H.L., Otto, E., Long, Z., Chiang, Y., McGarrity, G.J., Muul, L.M, Katz, D., Blaese, R.M., and Oldfield, E.H. (1997) Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat. Med. 3,1354 -1361.[CrossRef][Web of Science][Medline]
Reist, C.J., Archer, G.E., Kurpad, S.N., Wikstrand, C.J.,
Vaidyanathan, G., Willingham, M.C., Moscatello, D.K., Wong, A.J., Bigner,
D.D., and Zalutsky, M.R. (1995) Tumor-specific anti-epidermal
growth factor receptor variant III monoclonal antibodies: Use of the tyramine
cellobiose radioiodination method enhances cellular retention and uptake in
tumor xenografts. Cancer Res.
55,4375
-4382.
Reulen, H.J., Graber, S., Huber, P., and Ito, U. (1988) Factors affecting the extension of peritumoural brain oedema. A CT-study. Acta Neurochir. (Wien.) 95, 19-24.[CrossRef][Medline]
Riva, P., Franceschi, G., Arista, A., Frattarelli, M., Riva, N., Cremonini, A.M., Guiliani, G., and Casi, M. (1997) Local application of radiolabeled mon oclonal antibodies in the treatment of high grade malignant gliomas: A six year clinical experience. Cancer 80,2733 -2742.[CrossRef][Web of Science][Medline]
Salcman, M. (1994) The value of cytoreductive surgery. Clin. Neurosurg. 41,464 -488.[Medline]
Shapiro, W.R., Green, S.B., Burger, P.C., Selker, R.G., VanGilder, J.C., Robert son, J.T., Mealey, J., Jr., Ransohff, J., and Mahaley, M.S., Jr. (1992) A ran domized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5–fluorouracil, for newly diagnosed patients with malignant glioma. J. Neurosurg. 76,772 -781.[Web of Science][Medline]
Stewart, L.A. (2002) Chemotherapy in adult high-grade glioma: A systematic review and meta-analysis of individual patient data from 12 ran domised trials. Lancet 359,1011 -1018.[CrossRef][Web of Science][Medline]
Valtonen, S., Timonen, U., Toivanen, P., Kalimo, H., Kivipelto, L., Heiskanen, O., Unsgaard, G., and Kuurne, T. (1997) Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: A randomized double-blind study. Neurosurgery 41, 44-49.[CrossRef][Web of Science][Medline]
Walker, M.D., Green, S.B., Byar, D.P., Alexander, E., Jr., Batzdorf, U., Brooks, W.H., Hunt, W.E., MacCarty, C.S., Mahaley, M.S., Mealey, J., Jr., Owens, G., Ransohoff, J., 2nd, Robertson, J.T. Shapiro, W.R., Smith, K.R., Jr., Wilson, C.B., and Strike, T.A. (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N. Engl. J. Med. 303,1323 -1329.[Abstract]
Wersall, P., Ohlsson, I., Biberfeld, P., Collins, V.P., von Krusenstjerna, S., Larsson, S., Mellstedt, H., and Boethius, J. (1997) Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma. Cancer Immunol. Immunother. 44,157 -164.[CrossRef][Web of Science][Medline]
Westphal, M., and Giese, A. (1999) Local control of gliomas: The next best step—a good step? Front. Radiat. Ther. Oncol. 33,214 -226.[Medline]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Karpel-Massler, U. Schmidt, A. Unterberg, and M.-E. Halatsch Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand? Mol. Cancer Res., July 1, 2009; 7(7): 1000 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stupp, F. Roila, and On behalf of the ESMO Guidelines Working Group Malignant glioma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv126 - iv128. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Quinn, S. X. Jiang, J. Carter, D. A. Reardon, A. Desjardins, J. J. Vredenburgh, J. N. Rich, S. Gururangan, A. H. Friedman, D. D. Bigner, et al. Phase II Trial of Gliadel plus O6-Benzylguanine in Adults with Recurrent Glioblastoma Multiforme Clin. Cancer Res., February 1, 2009; 15(3): 1064 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Linnebank, A. Semmler, S. Moskau, Y. Smulders, H. Blom, and M. Simon The methylenetetrahydrofolate reductase (MTHFR) variant c.677C>T (A222V) influences overall survival of patients with glioblastoma multiforme Neuro-oncol, August 1, 2008; 10(4): 548 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Y. Wen and S. Kesari Malignant Gliomas in Adults N. Engl. J. Med., July 31, 2008; 359(5): 492 - 507. [Full Text] [PDF]
|
|
|
|
|
|
D. A. Reardon, M. R. Zalutsky, G. Akabani, R. E. Coleman, A. H. Friedman, J. E. Herndon II, R. E. McLendon, C. N. Pegram, J. A. Quinn, J. N. Rich, et al. A pilot study: 131I-Antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost Neuro-oncol, April 1, 2008; 10(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Buckner, P. D. Brown, B. P. O'Neill, F. B. Meyer, C. J. Wetmore, and J. H. Uhm Central Nervous System Tumors Mayo Clin. Proc., October 1, 2007; 82(10): 1271 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Ewend, S. Brem, M. Gilbert, R. Goodkin, P. L. Penar, M. Varia, S. Cush, and L. A. Carey Treatment of Single Brain Metastasis with Resection, Intracavity Carmustine Polymer Wafers, and Radiation Therapy Is Safe and Provides Excellent Local Control Clin. Cancer Res., June 15, 2007; 13(12): 3637 - 3641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kunwar, M. D. Prados, S. M. Chang, M. S. Berger, F. F. Lang, J. M. Piepmeier, J. H. Sampson, Z. Ram, P. H. Gutin, R. D. Gibbons, et al. Direct Intracerebral Delivery of Cintredekin Besudotox (IL13-PE38QQR) in Recurrent Malignant Glioma: A Report by the Cintredekin Besudotox Intraparenchymal Study Group J. Clin. Oncol., March 1, 2007; 25(7): 837 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Otterson, M. A. Villalona-Calero, S. Sharma, M. G. Kris, A. Imondi, M. Gerber, D. A. White, M. J. Ratain, J. H. Schiller, A. Sandler, et al. Phase I Study of Inhaled Doxorubicin for Patients with Metastatic Tumors to the Lungs Clin. Cancer Res., February 15, 2007; 13(4): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Weingart, S. A. Grossman, K. A. Carson, J. D. Fisher, S. M. Delaney, M. L. Rosenblum, A. Olivi, K. Judy, S. B. Tatter, and M. E. Dolan Phase I Trial of Polifeprosan 20 With Carmustine Implant Plus Continuous Infusion of Intravenous O6-Benzylguanine in Adults With Recurrent Malignant Glioma: New Approaches to Brain Tumor Therapy CNS Consortium Trial J. Clin. Oncol., February 1, 2007; 25(4): 399 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Bodell, A. P. Bodell, and D. D. Giannini Levels and distribution of BCNU in GBM tumors following intratumoral injection of DTI-015 (BCNU-ethanol) Neuro-oncol, January 1, 2007; 9(1): 12 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. ter Horst, S. M. Verwijnen, E. Brouwer, R. C. Hoeben, M. de Jong, B. H.C.G.M. de Leeuw, and P. A.E. Sillevis Smitt Locoregional Delivery of Adenoviral Vectors J. Nucl. Med., September 1, 2006; 47(9): 1483 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Olesen, M. G Baker, T. Freund, M. di Luca, J. Mendlewicz, I. Ragan, and M. Westphal Consensus document on European brain research J. Neurol. Neurosurg. Psychiatry, August 1, 2006; 77(suppl_1): i1 - i49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Reardon, J. N. Rich, H. S. Friedman, and D. D. Bigner Recent Advances in the Treatment of Malignant Astrocytoma J. Clin. Oncol., March 10, 2006; 24(8): 1253 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Gilbert New treatments for malignant gliomas: careful evaluation and cautious optimism required. Ann Intern Med, March 7, 2006; 144(5): 371 - 373. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stupp, M. E. Hegi, M. J. van den Bent, W. P. Mason, M. Weller, R. O. Mirimanoff, J. G. Cairncross, and on behalf of the European Organisation for Researc Changing paradigms--an update on the multidisciplinary management of malignant glioma. Oncologist, February 1, 2006; 11(2): 165 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Combs, C. Thilmann, L. Edler, J. Debus, and D. Schulz-Ertner Efficacy of Fractionated Stereotactic Reirradiation in Recurrent Gliomas: Long-Term Results in 172 Patients Treated in a Single Institution J. Clin. Oncol., December 1, 2005; 23(34): 8863 - 8869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brem, S. A. Grossman, K. A. Carson, P. New, S. Phuphanich, J. B. Alavi, T. Mikkelsen, J. D. Fisher, and for the New Approaches to Brain Tumor Therapy CNS Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma Neuro-oncol, July 1, 2005; 7(3): 246 - 253. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M. Chang, I. F. Parney, W. Huang, F. A. Anderson Jr, A. L. Asher, M. Bernstein, K. O. Lillehei, H. Brem, M. S. Berger, E. R. Laws, et al. Patterns of Care for Adults With Newly Diagnosed Malignant Glioma JAMA, February 2, 2005; 293(5): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Benny, M. Duvshani-Eshet, T. Cargioli, L. Bello, A. Bikfalvi, R. S. Carroll, and M. Machluf Continuous Delivery of Endogenous Inhibitors from Poly(Lactic-Co-Glycolic Acid) Polymeric Microspheres Inhibits Glioma Tumor Growth Clin. Cancer Res., January 15, 2005; 11(2): 768 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Weber and E. A. Goebel Cerebral edema associated with Gliadel wafers: Two case studies Neuro-oncol, January 1, 2005; 7(1): 84 - 89. [Abstract] [PDF]
|
|
|
|
 |
|
 B. J. May, M. Guarnieri, B. S. Carson Sr, A. Bachani, and G. I. Jallo Long-term Effects of Carboplatin Brainstem Infusions on Hearing Thresholds in Monkeys Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1411 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Hall, B. A. Moffat, J. Stojanovska, T. D. Johnson, Z. Li, D. A. Hamstra, A. Rehemtulla, T. L. Chenevert, J. Carter, D. Pietronigro, et al. Therapeutic Efficacy of DTI-015 using Diffusion Magnetic Resonance Imaging as an Early Surrogate Marker Clin. Cancer Res., December 1, 2004; 10(23): 7852 - 7859. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
