Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine- DNA Methyltransferase as a Potential Biomarker

被引:138
作者
Pietanza, M. Catherine [1 ]
Kadota, Kyuichi [2 ]
Huberman, Kety
Sima, Camelia S. [3 ]
Fiore, John J. [1 ]
Sumner, Dyana K. [1 ]
Travis, William D. [2 ]
Heguy, Adriana
Ginsberg, Michelle S. [4 ]
Holodny, Andrei I. [4 ]
Chan, Timothy A. [5 ,6 ]
Rizvi, Naiyer A. [1 ]
Azzoli, Christopher G. [1 ]
Riely, Gregory J. [1 ]
Kris, Mark G. [1 ]
Krug, Lee M. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA
[3] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA
[4] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY USA
[5] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol & Human Oncol, New York, NY USA
[6] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Pathogenesis Program, New York, NY USA
关键词
BRONCHOGENIC CARCINOMA; METHYLATION PATTERNS; THERAPY; GLIOMA; TUMORS; GLIOBLASTOMA; METASTASES; CLEAVAGE; MGMT;
D O I
10.1158/1078-0432.CCR-11-2059
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC). Experimental Design: 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. Results: 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). Conclusion: Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC. Clin Cancer Res; 18(4); 1138-45. (C)2012 AACR.
引用
收藏
页码:1138 / 1145
页数:8
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