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"
Altmetric Score
MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Adriana Heguy
    85 Heguy
  3. Timothy Chan
    215 Chan
  4. Michelle S Ginsberg
    158 Ginsberg
  5. Lee M Krug
    211 Krug
  6. Christopher G Azzoli
    105 Azzoli
  7. John J Fiore
    7 Fiore
  8. Naiyer A Rizvi
    156 Rizvi
  9. Maria C Pietanza
    115 Pietanza
  10. William D Travis
    548 Travis
  11. Gregory J Riely
    344 Riely
  12. Dyana K Sumner
    5 Sumner
  13. Andrei Holodny
    136 Holodny
  14. Kyuichi Kadota
    82 Kadota
  15. Mark Kris
    598 Kris