Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma Journal Article


Authors: Clarke, J. L.; Iwamoto, F. M.; Sul, J.; Panageas, K.; Lassman, A. B.; DeAngelis, L.; Hormigo, A.; Nolan, C. P.; Gavrilovic, I.; Karimi, S.; Abrey, L. E.
Article Title: Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma
Abstract: Purpose: Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma (GBM) by increasing the therapeutic index, overcoming common mechanisms of temozolomide resistance, or both. The goal of this randomized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM. Patients and Methods: Adult patients with newly diagnosed GBM were randomly assigned to receive standard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense (150 mg/m<sup>2</sup> days 1 to 7 and 15 to 21) or metronomic (50 mg/m<sup>2</sup> continuous daily) temozolomide. Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression. The primary end point was overall survival (OS) at 1 year. Tumor tissue was assayed to determine O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Results: Eighty-five eligible patients were enrolled; 42 were randomly assigned to dose-dense and 43 to metronomic temozolomide. The 1-year survival rate was 80% for the dose-dense arm and 69% for the metronomic arm; median OS was 17.1 months (95% CI, 14.0 to 28.1 months) and 15.1 months (95% CI, 12.3 to 18.9 months), respectively. The most common toxicities were myelosuppression (leukopenia, neutropenia, and thrombocytopenia) and elevated liver enzymes. Pseudoprogression was observed in 37% of assessable patients and may have had an impact on estimates of progression-free survival (6.6 months in the dose-dense arm and 5.0 months in the metronomic arm). Conclusion: Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity. The dose-dense regimen appears promising, with 1-year survival of 80%. © 2009 by American Society of Clinical Oncology.
Keywords: adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; aged; middle aged; survival rate; major clinical study; methylation; overall survival; promoter region; clinical trial; constipation; disease course; drug tolerability; fatigue; neutropenia; dose response; side effect; adjuvant therapy; cancer adjuvant therapy; cancer patient; cancer radiotherapy; comparative study; chemotherapy, adjuvant; radiotherapy, adjuvant; temozolomide; nuclear magnetic resonance imaging; brain tumor; brain neoplasms; magnetic resonance imaging; prospective study; prospective studies; gene; dacarbazine; progression free survival; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; bone marrow suppression; leukopenia; nausea; randomized controlled trial; thrombocytopenia; vomiting; drug administration schedule; alkylating agent; pneumocystis pneumonia; pathology; aminotransferase blood level; lymphocytopenia; kaplan-meiers estimate; disease progression; adjuvant chemotherapy; glioblastoma; antineoplastic agents, alkylating; drug derivative; patient compliance; methylated dna protein cysteine methyltransferase; kaplan meier method; aminotransferase; isotretinoin; liver enzyme; mgmt gene; tumor growth; drug administration
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-08-10
Start Page: 3861
End Page: 3867
Language: English
DOI: 10.1200/jco.2008.20.7944
PUBMED: 19506159
PROVIDER: scopus
PMCID: PMC2727290
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jennifer L Clarke
    11 Clarke
  2. Fabio M Iwamoto
    36 Iwamoto
  3. Andrew Lassman
    107 Lassman
  4. Sasan Karimi
    97 Karimi
  5. Adilia Hormigo
    48 Hormigo
  6. Joohee Sul
    6 Sul
  7. Lauren E Abrey
    272 Abrey
  8. Katherine S Panageas
    331 Panageas
  9. Craig Nolan
    44 Nolan