Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA.
Clin Cancer Res. 2012 Feb 15;18(4):1138-45. doi: 10.1158/1078-0432.CCR-11-2059. Epub 2012 Jan 6.
This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC).
Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m(2)/d for 21 days of a 28-day cycle. The primary endpoint was the overall response rate [ORR; complete response (CR) plus partial response (PR)], which was evaluated separately in sensitive and refractory cohorts. In the available tissue, we assessed O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status by PCR and MGMT expression by immunohistochemistry.
Sixty-four patients were accrued: 48 patients in the sensitive cohort and 16 in the refractory group. One CR and 10 PRs were noted in sensitive patients [ORR, 23%; 95% confidence interval (CI), 12%-37%]. Two PRs were seen in the refractory cohort (ORR, 13%; 95% CI, 2%-38%). As second- and third-line treatment, the ORR was 22% (95% CI, 9%-40%) and 19% (95% CI, 7%-36%), respectively. Among patients with target brain lesions, 38% had a CR or PR (95% CI, 14%-68%). Grade ≥3 thrombocytopenia and neutropenia were observed in nine patients (14%). A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT (38% vs. 7%; P = 0.08).
Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC.
本Ⅱ期研究旨在评估替莫唑胺治疗复发性小细胞肺癌（SCLC）患者的疗效。
接受过一或两个化疗方案治疗后疾病进展的患者接受替莫唑胺 75mg/m²/天治疗，每 21 天为一个 28 天周期。主要终点为总缓解率（ORR；完全缓解（CR）加部分缓解（PR）），在敏感和难治性亚组中分别评估。在可获得的组织中，我们通过 PCR 评估 O(6)-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化状态，并用免疫组化法评估 MGMT 表达。
共入组 64 例患者：敏感亚组 48 例，难治性组 16 例。敏感患者中 1 例 CR 和 10 例 PR[ORR，23%；95%置信区间（CI），12%-37%]。难治性组中 2 例 PR（ORR，13%；95% CI，2%-38%）。作为二线和三线治疗，ORR 分别为 22%（95% CI，9%-40%）和 19%（95% CI，7%-36%）。有目标脑转移病灶的患者中，38%有 CR 或 PR（95% CI，14%-68%）。9 例患者（14%）出现≥3 级血小板减少和中性粒细胞减少。MGMT 甲基化的病例比未甲基化的病例有更高的缓解率（38%比 7%；P=0.08）。
替莫唑胺在复发性 SCLC 中有活性，特别是对脑转移。替莫唑胺的反应可能与 SCLC 中的 MGMT 甲基化相关。
