Fondazione Istituto Neurologico Carlo Besta, IRCCS, Milan, Italy.
Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy.
J Neurooncol. 2019 May;142(3):455-462. doi: 10.1007/s11060-019-03116-z. Epub 2019 Feb 6.
Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.
In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.
Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.
Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.
This study is registered with ClinicalTrials.gov, number NCT01989884.
胶质母细胞瘤（GBM）是所有恶性神经胶质瘤中最具侵袭性和最常见的亚型。在复发时，治疗选择有限。奥沙利铂是一种第二代紫杉烷，在临床前和 I 期临床试验中显示出有效性。本研究旨在评估奥沙利铂在手术后和一线治疗后复发的 GBM 患者中的潜在治疗活性。
在这项 II 期研究中，根据两阶段设计，手术后或活检证实为 GBM 复发、标准放疗和替莫唑胺化疗的成年患者符合入选条件。入组患者接受奥沙利铂 75mg/m 静脉输注，每 3 周一次，直至疾病进展。该研究的主要目的是评估奥沙利铂在入组后 6 个月时无进展生存期（PFS）方面的疗效。次要终点包括 PFS、入组后 9 个月的总生存期、客观缓解率、依从性和安全性。
2013 年 11 月 26 日至 2015 年 12 月 12 日，在 6 个中心共招募了 40 名患者。在第一阶段，在分析的 35 名患者中，有 4 名（11.4%）患者在入组后 6 个月时存活且无进展，低于继续第二阶段研究所需的最少事件数（7 例）。最主要的毒性反应为中性粒细胞减少和肝毒性，发生率为 13.2%，白细胞减少发生率为 15.8%。
奥沙利铂总体治疗未能显示在复发性 GBM 患者中有显著的活性。然而，在有限数量的患者中，该药物产生了持久的疗效。
本研究在 ClinicalTrials.gov 注册，编号为 NCT01989884。
