L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: A phase i study

Leena Kankaanranta, Tiina Seppälä, Hanna Koivunoro, Petteri Välimäki, Annette Beule, Juhani Collan, Mika Kortesniemi, Jouni Uusi-Simola, Petri Kotiluoto, Iiro Auterinen, Tom Sern, Anders Paetau, Kauko Saarilahti, Sauli Savolainen, Heikki Joensuu

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    Abstract

    Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of l-boronophenylalanine-fructose (l-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of l-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated l-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of l-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

    Original languageEnglish
    Pages (from-to)369-376
    Number of pages8
    JournalInternational Journal of Radiation Oncology Biology Physics
    Volume80
    Issue number2
    DOIs
    Publication statusPublished - 1 Jun 2011
    MoE publication typeA1 Journal article-refereed

    Keywords

    • Anaplastic astrocytoma
    • Boron neutron capture therapy
    • Boronophenylalanine
    • Brain tumor
    • Glioblastoma

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  • Cite this

    Kankaanranta, L., Seppälä, T., Koivunoro, H., Välimäki, P., Beule, A., Collan, J., Kortesniemi, M., Uusi-Simola, J., Kotiluoto, P., Auterinen, I., Sern, T., Paetau, A., Saarilahti, K., Savolainen, S., & Joensuu, H. (2011). L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: A phase i study. International Journal of Radiation Oncology Biology Physics, 80(2), 369-376. https://doi.org/10.1016/j.ijrobp.2010.02.031, https://doi.org/10.1016/j.ijrobp.2010.02.031