原发性中枢神经系统淋巴瘤：化疗后采用输注溴脱氧尿苷联合全脑加速分割放射治疗的I期评估

Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy.

作者信息

Dabaja Bouthaina S, McLaughlin Peter, Ha Chul S, Pro Barbara, Meyers Christina A, Seabrooke Lee F, Wilder Richard B, Kyritsis Athanassios P, Preti H Alejandro, Yung W K Alfred, Levin Victor, Cabanillas Fernando, Cox James D

机构信息

Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Cancer. 2003 Sep 1;98(5):1021-8. doi: 10.1002/cncr.11627.

DOI:10.1002/cncr.11627

PMID:12942571

Abstract

BACKGROUND

The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL).

METHODS

Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment.

RESULTS

Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment.

CONCLUSIONS

Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.

摘要

背景

本研究旨在确定在化疗后给予加速分割全脑放疗（WBRT）时，静脉输注5-溴-2'-脱氧尿苷（溴脱氧尿苷；BUdR）治疗原发性中枢神经系统淋巴瘤（PCNSL）的最大耐受剂量（MTD）、毒性及疗效。

方法

1994年至1996年间，12例未经治疗且经组织学确诊的PCNSL患者进入本研究。化疗方案为一个疗程的异环磷酰胺、阿霉素、地塞米松、阿糖胞苷及顺铂（IDHAP）加用高剂量甲氨蝶呤（HD-MTX）。IDHAP方案包括：阿霉素剂量为1.5 mg/m²/天，持续静脉输注4天；地塞米松剂量为40 mg静脉注射，第1 - 5天使用；阿糖胞苷剂量为2000 mg/m²静脉注射，在顺铂治疗后第5天使用；顺铂剂量为25 mg/m²/天，持续静脉输注4天。HD-MTX在IDHAP治疗后的第10天至第14天静脉注射，剂量为3.5 g/m²。BUdR在WBRT前2 - 3天进行48小时静脉持续输注，然后在WBRT期间每周一次。剂量递增从第1组的1.5 g/m²/天开始，随后每次递增0.3 g/m²/天。WBRT剂量为45格雷（Gy），每天两次，每次1.5 Gy，每周5天。在治疗前、治疗期间和治疗后进行神经认知测试。

结果

12例进入研究的患者中有9例接受了BUdR治疗。第1组的3例患者中有1例在治疗完成后2个月内发生了白质脑病（LEP），这是一种剂量限制性毒性（DLT）。因此，下一组接受相同剂量水平。由于第2组未观察到毒性，第3组接受的BUdR剂量为1.8 g/m²/天。在第3组完成入组后不久，又有3例患者发生LEP，其中包括2例来自第1组且接受过1.5 g/m²/天剂量的患者。因此，DLT发生在1.5 g/m²/天的剂量水平，即本研究的起始剂量。结果，试验停止。12例患者中有8例达到完全缓解，3例达到部分缓解，1例患者在疗效评估前死亡。