Abstract
In a previous study we applied a three-step avidin–biotin pretargeting approach to target 90Y-biotin to the tumour in patients with recurrent high grade glioma. The encouraging results obtained in this phase I–II study prompted us to apply the same approach in an adjuvant setting, to evaluate (i) time to relapse and (ii) overall survival. We enrolled 37 high grade glioma patients, 17 with grade III glioma and 20 with glioblastoma, in a controlled open non-randomized study. All patients received surgery and radiotherapy and were disease-free by neuroradiological examinations. Nineteen patients (treated) received adjuvant treatment with radioimmunotherapy. In the treated glioblastoma patients, median disease-free interval was 28 months (range=9–59); median survival was 33.5 months and one patient is still without evidence of disease. All 12 control glioblastoma patients died after a median survival from diagnosis of 8 months. In the treated grade III glioma patients median disease-free interval was 56 months (range=15–60) and survival cannot be calculated as only two, within this group, died. Three-step radioimmunotherapy promises to have an important role as adjuvant treatment in high grade gliomas, particularly in glioblastoma where it impedes progression, prolonging time to relapse and overall survival. A further randomized trial is justified.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Altman DG, Bland JM (1999) Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ 318 (7192): 1209
Beaumier PL, Axworthy DB, Fritzberg AR, Hylarides MD, Mallet RW, Theodore LJ, Gustavson LM, Su F-M, Reno JM (1995) The pharmacology of pretargeting components: optimizing therapeutic targeting. Q J Nucl Med 39: 20
Burger PC (1983) Pathologic anatomy and CT correlations in the glioblastoma multiforme. Appl Neurophysiol 46: 180–187
Cremonesi M, Ferrari M, Chinol M, Stabin MG, Grana C, Prisco G, Robertson C, Tosi G, Paganelli G (1999) Three-step radioimmunotherapy with yttrium-90-biotin: dosimetry and pharmacokinetics in cancer patients. Eur J Nucl Med 26: 110–120
Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM (1992) In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256: 1550–1552
Davison AC, Hinkley DV (1997) Bootstrap methods and their application (Chapter 4) Cambridge Series in Statistical and Probabilistic Mathemathics. Cambridge, UK: Cambridge University Press
Florell RC, Macdonald DR, Irish WD, Bernstein M, Leibel SA, Gutin PH, Cairncross JG (1992) Selection bias, survival, and brachytherapy for glioma. J Neurosurg 76: 179–183
Goodwin DA (1987) Pharmacokinetics and antibodies. J Nucl Med 28: 1358–1362
Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W (1988) Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. J Nucl Med 29: 226–234
Hnatowich DJ, Virzi F, Rusckowski M (1987) Investigations of avidin and biotin for imaging applications. J Nucl Med 28: 1294–1302
Kalofonos HP, Rusckowski M, Siebecker DA, Sivolapenko GB, Snooke D, Lavender JP, Epenetos AA, Hnatowich DJ (1990) Imaging of tumour in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communication. J Nucl Med 31: 1791–1796
Larson SM (1990) Clinical radioimmunodetection,. 1978–1988: overview and suggestions for standardization of clinical trials, Cancer Res 50: 892–898
Leibel SA, Sheline GE (1987) Radiation therapy for neoplasms of the brain. J Neurosurg 66: 1–22
Magnani P, Paganelli G, Modorati G, Zito F, Songini C, Sudati F, Koch P, Maecke HR, Brancato R, Siccardi AG, Fazio F (1996) Quantitative comparison of direct antibody labeling and tumor pretargeting in uveal melanoma. J Nucl Med 37: 967–971
Mahaley Jr MS, Mettlin C, Natarajan N, Laws Jr ER, Peace BB (1989) National survey of patterns of care for brain-tumor patients. J Neurosurg 71: 826–836
O'Reilly SM, Newsland ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P (1993) Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer 29: 940–942
Paganelli G, Chinol M, Maggiolo M, Sidoli A, Corti A, Baroni S, Siccardi AG (1997) The three-step pretargeting approach reduces the human anti-mouse antibody response in patients submitted to radioimmunoscintigraphy and radioimmunotherapy. Eur J Nucl Med 24: 350–351
Paganelli G, Grana C, Chinol M, Cremonesi M, De Cicco C, De Braud F, Robertson C, Zurrida S, Casadio C, Zoboli S, Siccardi AG, Veronesi U (1999) Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin. Eur J Nucl Med 26: 348–357
Paganelli G, Magnani P, Zito F, Lucignani G, Sudati F, Turci G, Motti E, Terreni M, Pollo B, Giovannelli M, Canal N, Scotti G, Comi G, Koch P, Maecke HR, Fazio F (1994) Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO- biotin. Eur J Nucl Med 21: 314–321
Paganelli G, Magnani P, Zito F, Villa E, Stella M, Sudati F, Lopalco L, Rossetti C, Malcovati M, Chiolerio F, Seccamani E, Siccardi AG, Fazio F (1991) Three-step monoclonal antibody tumour targeting in carcinoembryonic antigen-positive patients. Cancer Res 51: 5960–5966
Paganelli G, Orecchia R, Jereczek-Fossa B, Grana C, Cremonesi M, de Braud F, Tradati N, Chinol M (1998) Combined treatment of advanced oropharyngeal cancer with external radiotherapy and three-step radioimmunotherapy. Eur J Nucl Med 25: 1336–1339
Paganelli G, Pervez S, Siccardi AG, Rowlinson G, Deleide G, Chiolerio F, Malcovati M, Scassellati GA, Epenetos AA (1990) Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies. Int J Cancer 45: 1184–1189
Paganelli G, Riva P, Deleide G, Clivio A, Chiolerio F, Scassellati GA, Malcovati M, Siccardi AG (1988) In vivo labelling of biotinylated monoclonal antibodies by radioactive avidin: a strategy to increase tumour radiolocalisation. Int J Cancer 2: 121–125
Riva P, Arista A, Tison V, Sturiale C, Franceschi G, Spinelli A, Riva N, Casi N, Moscatelli G, Frattarelli M (1994) Intralesional radioimmunotherapy of malignant gliomas: an effective treatment in recurrent tumors. Cancer 73: 1076–1082
Roth JA, Cristiano RJ (1997) Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 88: 21–39
Salazar O, Rubin P, Feldstein M, Pizzutiello R (1979) High dose radiation therapy in the treatment of malignant gliomas: final report. Int J Rad Oncol Biol Phys 5: 1733–1740
Salcman M (1990) Epidemiology and factors affecting survival. In Malignant Cerebral Glioma Apuzzo MLJ (ed), pp 95–110, American Association of Neurological Surgeons. Illinois: Park Ridge
Sung C, van Osdol WW (1995) Pharmacokinetic comparison of direct antibody targeting with pretargeting protocols based on streptavidin-biotin binding. J Nucl Med 36: 867–876
Therneau TM, Grambsch PM (2000) Modeling Survival Data. pp. 7–76, Heidelberg, Germany: Springer
Walker AE, Robins M, Weinfeld FD (1985) Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 35: 219–226
Wilchek M, Bayer EA (1984) The avidin-biotin complex in immunology. Immunol Today 5: 39–43
Zalutsky MR, Moseley RP, Coakham HB, Coleman RE, Bigner DD (1989) Pharmacokinetics and tumour localization of 131I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracrianal malignancies. Cancer Res 49: 2807–2813
Acknowledgements
This work was supported by grants from the Italian Association for Cancer Research (AIRC). The Authors thank Mr Donald Ward for help with the English and Ms Eleonora Del Fabbro for editing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Grana, C., Chinol, M., Robertson, C. et al. Pretargeted adjuvant radioimmunotherapy with Yttrium-90-biotin in malignant glioma patients: A pilot study. Br J Cancer 86, 207–212 (2002). https://doi.org/10.1038/sj.bjc.6600047
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6600047
Keywords
This article is cited by
-
Enhancement of HIFU ablation by sonosensitizer-loading liquid fluorocarbon nanoparticles with pre-targeting in a mouse model
Scientific Reports (2019)
-
Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice
Nature Communications (2018)
-
Pretargeting in the context of theranostics and companion diagnostics in nuclear oncology
Clinical and Translational Imaging (2018)
-
Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models
Scientific Reports (2016)
-
Radioimmunotherapy of human tumours
Nature Reviews Cancer (2015)