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Pretargeted adjuvant radioimmunotherapy with Yttrium-90-biotin in malignant glioma patients: A pilot study

British Journal of Cancer volume 86, pages 207–212 (2002)Cite this article

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.

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References

  • Altman DG, Bland JM (1999) Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ 318 (7192): 1209

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Burger PC (1983) Pathologic anatomy and CT correlations in the glioblastoma multiforme. Appl Neurophysiol 46: 180–187

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Davison AC, Hinkley DV (1997) Bootstrap methods and their application (Chapter 4) Cambridge Series in Statistical and Probabilistic Mathemathics. Cambridge, UK: Cambridge University Press

    Book  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Goodwin DA (1987) Pharmacokinetics and antibodies. J Nucl Med 28: 1358–1362

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Hnatowich DJ, Virzi F, Rusckowski M (1987) Investigations of avidin and biotin for imaging applications. J Nucl Med 28: 1294–1302

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Larson SM (1990) Clinical radioimmunodetection,. 1978–1988: overview and suggestions for standardization of clinical trials, Cancer Res 50: 892–898

    Google Scholar 

  • Leibel SA, Sheline GE (1987) Radiation therapy for neoplasms of the brain. J Neurosurg 66: 1–22

    Article  CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Therneau TM, Grambsch PM (2000) Modeling Survival Data. pp. 7–76, Heidelberg, Germany: Springer

    Google Scholar 

  • Walker AE, Robins M, Weinfeld FD (1985) Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 35: 219–226

    Article  CAS  Google Scholar 

  • Wilchek M, Bayer EA (1984) The avidin-biotin complex in immunology. Immunol Today 5: 39–43

    Article  CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

Download references

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.

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Authors and Affiliations

  1. Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, Milano, I-20141, Italy

    C Grana, M Chinol, M Bartolomei, C De Cicco, M Fiorenza, M Gatti & G Paganelli

  2. Division of Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti 435, Milano, I-20141, Italy

    C Robertson & C Mazzetta

  3. Department of Pharmaceutical Science, University of Padova, Italy

    P Caliceti

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  1. C Grana
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  2. M Chinol
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  10. G Paganelli
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Correspondence to G Paganelli.

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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

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