van den Bent M J, Taphoorn M J B, Brandes A A, Menten J, Stupp R, Frenay M, Chinot O, Kros J M, van der Rijt C C D, Vecht Ch J, Allgeier A, Gorlia T
Department of Neuro-Oncology, University Hospital Rotterdam/Rotterdam Cancer Center, the Netherlands.
J Clin Oncol. 2003 Jul 1;21(13):2525-8. doi: 10.1200/JCO.2003.12.015.
Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy.
In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed.
Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression.
TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.
少突胶质细胞瘤是对化疗敏感的肿瘤，三分之二的患者对丙卡巴肼、洛莫司汀和长春新碱（PCV）联合化疗有反应。替莫唑胺（TMZ）是一种新型的烷基化和甲基化剂，已在复发性间变性星形细胞瘤患者中显示出高缓解率。我们研究了TMZ作为复发性少突胶质细胞瘤（OD）和混合性少突星形细胞瘤（OA）术后及放疗后的一线化疗药物。
在一项前瞻性、非随机、多中心的II期试验中，患者在28天周期的第1至5天接受200mg/m²的TMZ治疗，共12个周期。先前接受过手术和放疗后复发、磁共振成像（MRI）显示有可测量的强化病灶的患者符合本研究条件。有大病灶和占位效应或有新的临床神经功能缺损的患者不符合条件。对所有有反应患者的病理和MRI扫描进行集中审查。
纳入了38例符合条件的患者。3例患者的病理检查未证实存在OD或OA。TMZ一般耐受性良好。最常见的副作用是血液学方面的；只有1例患者因毒性而停止治疗。38例患者中有20例（52.6%）（95%确切置信区间，35.8%至69.0%）对TMZ有完全缓解（n = 10）或部分缓解。所有患者的中位进展时间为10.4个月，有反应患者为13.2个月。从治疗开始12个月时，40%的患者仍无进展。
TMZ在未经化疗的复发性OD患者中提供了优异的缓解率和良好的耐受性。有必要进行一项比较PCV与TMZ的随机III期研究。
