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动脉内注射卡铂作为复发性多形性胶质母细胞瘤的挽救治疗策略。

Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme.

作者信息

Fortin David, Morin Pierre-Aurèle, Belzile Francois, Mathieu David, Paré Francois-Michel

机构信息

Division of Neurosurgery and Neuro-Oncology, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada,

出版信息

J Neurooncol. 2014 Sep;119(2):397-403. doi: 10.1007/s11060-014-1504-4. Epub 2014 Jun 20.

Abstract

The first-line treatment of glioblastoma typically consists of a maximal surgical resection, followed by a combination of radio-chemotherapy with temozolomide. There is however no consensus regarding optimal therapeutic approaches at relapse. The following phase II study explored the therapeutic gain obtained when exposing these patients to a combination of intra-arterially administered carboplatin and melphalan at first or second relapse as a salvage treatment in recurrent glioblastoma. Fifty-one consecutive patients diagnosed with glioblastoma were accrued and offered this treatment at first or second relapse. A Karnofsky score of ≥ 60 was required, and when appropriate, patients were first reoperated prior to accrual. Patients enrolled were treated every 4 weeks (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria. Primary end point surrogates were overall survival from diagnosis and study entry. Median survival from diagnosis and study entry was 23 and 11 months, respectively. The median time to progression was 5.2 months. All patients enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was manageable, with an 8 % of grade II neutropenia, 12 % of grade II thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy represents an adequate option in the second-line treatment of recurrent glioblastoma. The adjunction of an osmotic permeabilization could be considered to further expand delivery, and hopefully improve survival in these patients.

摘要

胶质母细胞瘤的一线治疗通常包括最大程度的手术切除,随后是替莫唑胺同步放化疗。然而,对于复发时的最佳治疗方法尚无共识。以下这项II期研究探索了复发性胶质母细胞瘤患者在首次或第二次复发时接受动脉内注射卡铂和马法兰联合治疗作为挽救治疗所获得的治疗益处。连续纳入了51例诊断为胶质母细胞瘤的患者,并在首次或第二次复发时给予这种治疗。要求卡氏评分≥60分,适当情况下,患者在入组前先进行再次手术。入组患者每4周治疗1次(1个周期),最多治疗12个周期。采用麦克唐纳标准评估病情进展。主要终点替代指标是从诊断到入组研究的总生存期。从诊断到入组研究的中位生存期分别为23个月和11个月。中位疾病进展时间为5.2个月。所有入组患者至少接受了2个周期的治疗。血液学毒性可控,II级中性粒细胞减少症发生率为8%,II级血小板减少症发生率为12%,III级血小板减少症发生率为7%。这种治疗策略是复发性胶质母细胞瘤二线治疗的一种合适选择。可以考虑增加渗透通透化处理以进一步扩大给药范围,并有望提高这些患者的生存率。

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