Fuentes S, Chinot O, Dufour H, Paz-Paredes A, Métellus Ph, Barrie-Attarian M, Grisoli F
Service de Neurochirurgie (Pr. F. Grisoli), Hôpital de La Timone Adulte, rue Saint-Pierre, 13385 Marseille 5.
Neurochirurgie. 2004 Sep;50(4):461-7. doi: 10.1016/s0028-3770(04)98326-9.
Management of unresectable progressive meningioma remains controversial and constitutes a major challenge since therapeutic options including chemotherapy and hormone modulation are limited. Recent data have suggested that hydroxyurea treatment may have an antitumoral effect. The purpose of this prospective phase II study was to evaluate the efficacy of hydroxyurea treatment for unresectable progressive meningioma.
From 1997 to 1999, consecutive patients presenting unresectable meningioma with clinically and/or neuroradiologically documented progression were considered for entry into this protocol. Previous radiotherapy was not a mandatory inclusion criteria. Treatment consisted of continuous oral administration of hydroxyurea at a dose of 20 mg/kg per day. Follow-up assessment included physical examination, computed tomography (CT), and magnetic resonance imaging (MRI) performed every three months, as well as regular blood testing. The primary endpoint was documentation of objective response by MRI or CT.
The intent-to-treat population was 43 patients with at least 18 months follow-up. Median age was 60.4 years. Twenty-eight patients had undergone surgery following initial diagnosis. The meningioma was located in the skull base in 67% of patients. Histology was benign in 18 and atypical in 10. The eligible population included 36 patients with documented progressive disease at the time of inclusion; with progression documented clinically in 29 (67.5%) and/or radiologically in 20 (46%). In 7 patients, clinical or radiological progression could not be confirmed. The intent-to-treat analysis at median 26 months follow-up revealed objective response to hydroxyurea in only 3 patients (7%) including one on the basis of improvement in visual symptoms and two on MRI analysis. Progressive disease was observed clinically or radiologically in 26 patients (60.5%). Of the eligible population (n=36), 2 achieved an objective response and 13 (36%) exhibited stabilization under hydroxyurea therapy, while 21 (58%) progressed under treatment. Overall tolerance was good but anemia (grade I-II) and asthenia (grade I-II) were observed in 28% and 23.5% respectively. Treatment was discontinued in 3 patients because of chronic skin toxicity in one and anemia and asthenia in two.
Hydroxyurea treatment is of marginal efficacy for meningioma and must not be considered as an alternative if radiotherapy or surgery is feasible. New efficient medical treatments are still required for progressive meningiomas.
不可切除的进展性脑膜瘤的治疗仍存在争议，并且是一项重大挑战，因为包括化疗和激素调节在内的治疗选择有限。最近的数据表明，羟基脲治疗可能具有抗肿瘤作用。这项前瞻性II期研究的目的是评估羟基脲治疗不可切除的进展性脑膜瘤的疗效。
从1997年至1999年，连续出现不可切除的脑膜瘤且有临床和/或神经放射学记录的进展的患者被纳入本方案。既往放疗不是强制纳入标准。治疗包括每天口服20mg/kg剂量的羟基脲。随访评估包括体格检查、每三个月进行一次的计算机断层扫描（CT）和磁共振成像（MRI），以及定期血液检测。主要终点是通过MRI或CT记录客观缓解情况。
意向性分析人群为43例患者，至少随访18个月。中位年龄为60.4岁。28例患者在初次诊断后接受了手术。67%的患者脑膜瘤位于颅底。组织学检查18例为良性，10例为非典型。符合条件的人群包括36例在纳入时记录有疾病进展的患者；其中29例（67.5%）有临床记录的进展和/或20例（46%）有放射学记录的进展。7例患者的临床或放射学进展无法得到证实。中位随访26个月时的意向性分析显示，只有3例患者（7%）对羟基脲有客观缓解，其中1例基于视觉症状改善，2例基于MRI分析。26例患者（60.5%）出现临床或放射学疾病进展。在符合条件的人群（n = 36）中，2例获得客观缓解，13例（36%）在羟基脲治疗下病情稳定，而21例（58%）在治疗过程中病情进展。总体耐受性良好，但分别有28%和23.5%的患者出现贫血（I-II级）和乏力（I-II级）。3例患者因1例出现慢性皮肤毒性和2例出现贫血及乏力而停药。
羟基脲治疗脑膜瘤的疗效有限，如果放疗或手术可行，则不应将其视为替代治疗方法。进展性脑膜瘤仍需要新的有效药物治疗。
