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 Journal Article
| Authors: | Pietanza, M. C.; Kadota, K.; Huberman, K.; Sima, C. S.; Fiore, J. J.; Sumner, D. K.; Travis, W. D.; Heguy, A.; Ginsberg, M. S.; Holodny, A. I.; Chan, T. A.; Rizvi, N. A.; Azzoli, C. G.; Riely, G. J.; Kris, M. G.; Krug, L. M. |
| Article Title: | 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 |
| Abstract: | 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. ©2012 AACR. |
| Keywords: | adult; clinical article; controlled study; human tissue; protein expression; treatment outcome; treatment response; aged; constipation; disease course; fatigue; neutropenia; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; disease marker; drug targeting; temozolomide; anorexia; biological marker; drug eruption; multiple cycle treatment; phase 2 clinical trial; anemia; bone marrow suppression; etoposide; leukopenia; nausea; thrombocytopenia; cohort analysis; pneumocystis pneumonia; skull irradiation; drug dose escalation; febrile neutropenia; lymphocytopenia; chemotherapy induced emesis; lung small cell cancer; myelodysplastic syndrome; bone marrow biopsy; brain metastasis; ondansetron; cancer relapse; open study; methylated dna protein cysteine methyltransferase; infection prevention; cytopenia; enzyme assay; hematologic disease; protein methylation; desquamation; hypertransaminasemia |
| Journal Title: | Clinical Cancer Research |
| Volume: | 18 |
| Issue: | 4 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-02-15 |
| Start Page: | 1138 |
| End Page: | 1145 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-11-2059 |
| PROVIDER: | scopus |
| PUBMED: | 22228633 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "CODEN: CCREF" - "Source: Scopus" |
