l-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

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• 作者：Leena Kankaanranta M.D.^* ; Tiina Seppä ; lä ; Ph.D.^* ; ^† ; ; ^‡ ; ; Hanna Koivunoro M.Sci.^* ; ^† ; ; ^‡ ; ; Petteri Vä ; limä ; ki M.Sci^† ; ; ^‡ ; ; Annette Beule M.D.^¶ ; ; Juhani Collan M.D.^* ; Mika Kortesniemi Ph.D.^¶ ; ; Jouni Uusi-Simola Ph.D.^† ; ; ^¶ ; ; Petri Kotiluoto Ph.D.^§ ; ; Iiro Auterinen M.Sci.^§ ; ; Tom Serè ; n Lic.Tech.^§ ; ; Anders Paetau M.D.^** ; Kauko Saarilahti M.D.^* ; Sauli Savolainen Ph.D.^† ; ; ^¶ ; ; Heikki Joensuu M.D.^* ; ^{heikki.joensuu@hus.fi"" rel=""nofollow}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2011
• 出版时间：1 June 2011
• 年：2011
• 卷：80
• 期：2
• 页码：369-376
• 全文大小：227 K

文摘

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.