Fixed dose-rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma: a dose-finding study
Fixed dose-rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma: a dose-finding study
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DOI：
10.1007/s11060-007-9489-x
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发表时间：
2008-03-01
影响因子：
3.9
通讯作者：
Carapella, Carmine Maria
中科院分区：
文献类型：
--
作者：
Fabi, Alessandra;Mirri, Alessandra;Carapella, Carmine Maria
对于新诊断的多形性胶质母细胞瘤（GBM）患者，替莫唑胺同步化放疗是新的护理标准。在目前的I期研究中，我们研究了吉西他滨（一种具有放射增敏特性的细胞周期抗代谢药）与一线治疗中放疗（RT）的相关性。吉西他滨以每周10 mg/m2/min的固定剂量率给药，持续6周，从放疗前24-72 h开始，然后与放疗同时进行（每次2.0戈伊，总剂量60 Gy）。主要终点是确定剂量限制性毒性（DLT）和最大耐受剂量（MTD）。吉西他滨的计划剂量水平从200 mg/m2/周（水平1）开始，连续剂量递增25 mg/m2。入组了10例患者，均在术后患有可评价疾病。6例患者为男性，中位年龄为55岁（44-75岁），中位基线Karnofsky体力状态为85（70-100）。4名患者进入1级，1名患者因早期疾病进展而被排除在研究之外。在这个水平，三名患者中有两名发生了进行性神经功能恶化，可能与实验性治疗有关。在此基础上，吉西他滨剂量在后续步骤（水平-1）中谨慎降至175 mg/m2/周。在该节段入组的6例患者中未发生DLT。有趣的是，在该剂量下，仅报告了2例3级毒性（1例中性粒细胞减少症和1例血清转氨酶升高）。因此，在目前正在进行的II期研究中，推荐使用175 mg/m2/周的固定剂量率吉西他滨进行进一步评估。
In patients with newly diagnosed glioblastoma multiforme (GBM), concurrent chemo-radiotherapy with temozolomide is the new standard of care. In the present phase I study we investigated the association of gemcitabine, a cell-cycle antimetabolite with radiosensitizing properties, with radiotherapy (RT) in the first line treatment. Gemcitabine was delivered at a fixed dose-rate of 10 mg/m(2)/min weekly for 6 weeks starting 24-72 h prior to, and then concomitantly with RT (2.0 Gy per fraction, total dose 60 Gys). The primary end-point was the identification of dose-limiting toxicity (DLT), and maximum tolerated dose (MTD). Planned dose levels of gemcitabine started from 200 mg/m(2)/weekly (level 1), with sequential dose escalations of 25 mg/m(2). Ten patients were enrolled, all with evaluable disease after surgery. Six patients were male, median age was 55 years (44-75), and median baseline Karnofsky performance status was 85 (70-100). Four patients entered level 1, one patient being excluded from the study because of early disease progression. At this level, two of three patients developed progressive neurological deterioration, potentially related to the experimental treatment. On this basis gemcitabine dose was prudentially reduced to 175 mg/m(2)/weekly in the subsequent step (level -1). No DLT was encountered in the six patients enrolled at this level. Interestingly, at this dose only two grade three toxicities (one neutropenia and one raise in serum transaminases) were reported. Thus, fixed dose-rate gemcitabine at 175 mg/m(2)/weekly is the recommended regimen for further evaluation in a phase II study that is presently in progress.